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Xue S, Song F, Wei N, Liu Y, Liu M, Huang X, Zhang Y, Liu Y, Hao H, Zhang J. Study on Quality Evaluation of Er Miao San Based on HPLC Fingerprinting Combined With Multi-Indicator Content Determination. Biomed Chromatogr 2025; 39:e70000. [PMID: 39968959 DOI: 10.1002/bmc.70000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 01/03/2025] [Indexed: 02/20/2025]
Abstract
We aim to establish the fingerprint profile of Er Miao San (EMS) that aims to accurately evaluate the quality of EMS samples and to identify quality markers for different batches of EMS and explore its related targets and pathways for the treatment of rheumatoid arthritis. HPLC was employed with an Agilent C18 column. Cluster analysis and principal component analysis were conducted by using SPSS and SIMCA software. Network pharmacology techniques were utilized to explore the potential targets and pathways of EMS in the treatment of rheumatoid arthritis. The HPLC fingerprint profile of EMS was established, featuring a total of 15 common peaks, among which nine were identified. The 10 batches of medicinal materials could be clustered into three categories. With VIP > 1 as the criterion, four index differential components were screened out. These intersections were imported into the STRING database and Cytoscape software, resulting in 228 intersection targets. GO and KEGG enrichment analyses were performed on the related targets and pathways. The established method can effectively analyze the quality differences of EMS from different origins. The screened targets and pathways are of great significance for analyzing the differences in the treatment of rheumatoid arthritis by different batches of EMS.
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Affiliation(s)
- Shuyan Xue
- The Third Clinical College, Shanxi University of Chinese Medicine, Taiyuan, China
| | - Feichao Song
- School of Management, Shanxi Medical University, Taiyuan, China
| | - Na Wei
- School of Basic Medicine, Shanxi University of Chinese Medicine, Jinzhong, China
| | - Yuxuan Liu
- School of Management, Shanxi Medical University, Taiyuan, China
| | - Muchun Liu
- Academy of Medical Sciences, Shanxi Medical University, Taiyuan, China
| | - Xi Huang
- School of Management, Shanxi Medical University, Taiyuan, China
| | - Yumeng Zhang
- School of Basic Medicine, Shanxi University of Chinese Medicine, Jinzhong, China
| | - Yang Liu
- The Third Clinical College, Shanxi University of Chinese Medicine, Taiyuan, China
| | - Huiqin Hao
- The Third Clinical College, Shanxi University of Chinese Medicine, Taiyuan, China
| | - Junfeng Zhang
- The Third Clinical College, Shanxi University of Chinese Medicine, Taiyuan, China
- School of Management, Shanxi Medical University, Taiyuan, China
- School of Basic Medicine, Shanxi University of Chinese Medicine, Jinzhong, China
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Li S, Wang S, Zhang L, Wu X, Tian L, Zou J, Pi G. METTL3 methylated KIF15 promotes nasopharyngeal carcinoma progression and radiation resistance by blocking ATG7-mediated autophagy through the activation of STAT3 pathway. Transl Oncol 2025; 51:102161. [PMID: 39504712 PMCID: PMC11570775 DOI: 10.1016/j.tranon.2024.102161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Revised: 09/13/2024] [Accepted: 10/21/2024] [Indexed: 11/08/2024] Open
Abstract
BACKGROUND Resistance to radiotherapy is a major component in the failure of nasopharyngeal carcinoma (NPC) treatment. Enhancing autophagy in nasopharyngeal carcinoma may increase its radiation sensitivity, making it critical to find autophagy-modulating targets. METHODS The level of KIF15 was determined in NPC patients. Then, radiation-resistant NPC cells were produced to explore the mechanism in NPC. KIF15 was suppressed, and cell function and autophagy-related variables were examined in radiation-resistant NPC cells. Then the autophagy pathway was blocked, and the link between KIF15 and autophagy was confirmed. Finally, an NPC murine model was established, with tumors implanted in aberrant sites, and the relationship discovered at the cell level was confirmed in vivo. All statistical significance was determined using the student's t-test and one-way ANOVA. RESULTS Elevated amounts of KIF15 were discovered to be significantly expressed in NPC tissues and played a role in the radioresistance of NPC, a phenomenon attributed to METTL3-mediated m6A methylation. Blocking KIF15 resulted in decreased cell proliferation, increased cell death, and the activation of autophagy, ultimately making NPC more sensitive to radiation. This also resulted in decreased tumor development and increased levels of autophagy and apoptosis in vivo KIF15 interacted with STAT3, retaining it in the cytoplasm. Overexpression of STAT3 reversed the inhibitory effects of KIF15 knockdown on NPC and also reversed the influence of sh-KIF15 on autophagy activation. Inhibition of KIF15 decreased the inhibitory effect of STAT3 on ATG7, thereby upregulating autophagy activation in radio-resistant NPC cells. CONCLUSION The increased expression of KIF15 was found to be associated with the progression of NPC and play a role in the development of radioresistance in NPC. Inhibiting KIF15 was shown to impede tumor growth and improve the sensitivity of NPC to radiotherapy by triggering autophagy via the STAT3/ATG7 pathway.
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Affiliation(s)
- Siwei Li
- Department of Oncology, Huanggang Central Hospital of Yangtze University, No.126 Qi'an Road, Huanggang City, Hubei Province, 438000, PR China; Hubei Clinical Medical Research Center of Esophageal and Gastric Malignancy, Huanggang City, Hubei Province, 438021, PR China
| | - Shuibin Wang
- Department of Otolaryngology-Head and Neck Surgery, Huanggang Central Hospital of Yangtze University, No.126 Qi'an Road, Huanggang City, Hubei Province, 438000, PR China
| | - Lu Zhang
- School of Medicine, Wuhan University of Science and Technology, No.2 Huangjiahu West Road, Hongshan District, Wuhan City, Hubei Province, 430070, PR China
| | - Xiaofeng Wu
- Department of Otolaryngology-Head and Neck Surgery, Huanggang Central Hospital of Yangtze University, No.126 Qi'an Road, Huanggang City, Hubei Province, 438000, PR China
| | - Longfu Tian
- Department of Oncology, Huanggang Central Hospital of Yangtze University, No.126 Qi'an Road, Huanggang City, Hubei Province, 438000, PR China
| | - Jiahua Zou
- Department of Oncology, Huanggang Central Hospital of Yangtze University, No.126 Qi'an Road, Huanggang City, Hubei Province, 438000, PR China; Hubei Clinical Medical Research Center of Esophageal and Gastric Malignancy, Huanggang City, Hubei Province, 438021, PR China.
| | - Guoliang Pi
- Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.116 Zhuodaoquan South Road, Hongshan District, Wuhan City, Hubei Province, 430079, PR China.
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Qian JN, Kang YL, He YC, Hu HY. Topic Modeling Analysis of Chinese Medicine Literature on Gastroesophageal Reflux Disease: Insights into Potential Treatment. Chin J Integr Med 2024; 30:1128-1136. [PMID: 38850480 DOI: 10.1007/s11655-024-3800-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/01/2023] [Indexed: 06/10/2024]
Abstract
OBJECTIVE To analyze Chinese medicine (CM) prescriptions for gastroesophageal reflux disease (GERD), we model topics on GERD-related classical CM literature, providing insights into the potential treatment. METHODS Clinical guidelines were used to identify symptom terms for GERD, and CM literature from the database "Imedbooks" was retrieved for related prescriptions and their corresponding sources, indications, and other information. BERTopic was applied to identify the main topics and visualize the data. RESULTS A total of 36,207 entries are queried and 1,938 valid entries were acquired after manually filtering. Eight topics were identified by BERTopic, including digestion function abate, stomach flu, respiratory-related symptoms, gastric dysfunction, regurgitation and gastrointestinal dysfunction in pediatric patients, vomiting, stroke and alcohol accumulation are associated with the risk of GERD, vomiting and its causes, regurgitation, epigastric pain, and symptoms of heartburn. CONCLUSIONS Topic modeling provides an unbiased analysis of classical CM literature on GERD in a time-efficient and scale-efficient manner. Based on this analysis, we present a range of treatment options for relieving symptoms, including herbal remedies and non-pharmacological interventions such as acupuncture and dietary therapy.
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Affiliation(s)
- Jia-Nan Qian
- Department of Gastroenterology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
| | - Yan-Lan Kang
- Institute of AI and Robotics, Academy for Engineering & Technology, Fudan University, Shanghai, 200433, China
| | - You-Cheng He
- Clinical Research Center, Longhua Hospital, Shanghai, 200032, China
| | - Hong-Yi Hu
- Department of Gastroenterology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
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Ning N, Li X, Nan Y, Chen G, Huang S, Du Y, Gu Q, Li W, Yuan L. Molecular mechanism of Saikosaponin-d in the treatment of gastric cancer based on network pharmacology and in vitro experimental verification. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:8943-8959. [PMID: 38864908 DOI: 10.1007/s00210-024-03214-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 06/03/2024] [Indexed: 06/13/2024]
Abstract
The study aimed to utilize network pharmacology combined with cell experiments to research the mechanism of action of Saikosaponin-d in the treatment of gastric cancer. Drug target genes were obtained from the PubChem database and the Swiss Target Prediction database. Additionally, target genes for gastric cancer were obtained from the GEO database and the Gene Cards database. The core targets were then identified and further analyzed through gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and GESA enrichment. The clinical relevance of the core targets was assessed using the GEPIA and HPA databases. Molecular docking of drug monomers and core target proteins was performed using Auto Duck Tools and Pymol software. Finally, in vitro cellular experiments including cell viability, apoptosis, cell scratch, transwell invasion, transwell migration, qRT-PCR, and Western blot were conducted to verify these findings of network pharmacology. The network pharmacology analysis predicted that the drug monomers interacted with 54 disease targets. Based on clinical relevance analysis, six core targets were selected: VEGFA, IL2, CASP3, BCL2L1, MMP2, and MMP1. Molecular docking results showed binding activity between the Saikosaponin-d monomer and these core targets. Saikosaponin-d could inhibit gastric cancer cell proliferation, induce apoptosis, and inhibit cell migration and invasion.
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Affiliation(s)
- Na Ning
- College of Pharmacy, Ningxia Medical University, Yinchuan, 750004, Ningxia, China
| | - Xiangyang Li
- College of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan, 750004, Ningxia, China
| | - Yi Nan
- College of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan, 750004, Ningxia, China
| | - Guoqing Chen
- College of Pharmacy, Ningxia Medical University, Yinchuan, 750004, Ningxia, China
| | - Shicong Huang
- College of Pharmacy, Ningxia Medical University, Yinchuan, 750004, Ningxia, China
| | - Yuhua Du
- College of Pharmacy, Ningxia Medical University, Yinchuan, 750004, Ningxia, China
| | - Qian Gu
- College of Pharmacy, Ningxia Medical University, Yinchuan, 750004, Ningxia, China
| | - Weiqiang Li
- Department of Chinese Medical Gastrointestinal, TCM Hospital of Ningxia Medical University, Wuzhong, 751100, China.
| | - Ling Yuan
- College of Pharmacy, Ningxia Medical University, Yinchuan, 750004, Ningxia, China.
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Jin Z, Lan Y, Li J, Wang P, Xiong X. The role of Chinese herbal medicine in the regulation of oxidative stress in treating hypertension: from therapeutics to mechanisms. Chin Med 2024; 19:150. [PMID: 39468572 PMCID: PMC11520704 DOI: 10.1186/s13020-024-01022-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Accepted: 10/11/2024] [Indexed: 10/30/2024] Open
Abstract
BACKGROUND Although the pathogenesis of essential hypertension is not clear, a large number of studies have shown that oxidative stress plays an important role in the occurrence and development of hypertension and target organ damage. PURPOSE This paper systematically summarizes the relationship between oxidative stress and hypertension, and explores the potential mechanisms of Chinese herbal medicine (CHM) in the regulation of oxidative stress in hypertension, aiming to establish a scientific basis for the treatment of hypertension with CHM. METHODS To review the efficacy and mechanism by which CHM treat hypertension through targeting oxidative stress, data were searched from PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, the Chinese National Knowledge Infrastructure, the VIP Information Database, the Chinese Biomedical Literature Database, and the Wanfang Database from their inception up to January 2024. NPs were classified and summarized by their mechanisms of action. RESULTS In hypertension, the oxidative stress pathway of the body is abnormally activated, and the antioxidant system is inhibited, leading to the imbalance between the oxidative and antioxidative capacity. Meanwhile, excessive production of reactive oxygen species can lead to endothelial damage and vascular dysfunction, resulting in inflammation and immune response, thereby promoting the development of hypertension and damaging the heart, brain, kidneys, blood vessels, and other target organs. Numerous studies suggested that inhibiting oxidative stress may be the potential therapeutic target for hypertension. In recent years, the clinical advantages of traditional Chinese medicine (TCM) in the treatment of hypertension have gradually attracted attention. TCM, including active ingredients of CHM, single Chinese herb, TCM classic formula and traditional Chinese patent medicine, can not only reduce blood pressure, improve clinical symptoms, but also improve oxidative stress, thus extensively affect vascular endothelium, renin-angiotensin-aldosterone system, sympathetic nervous system, target organ damage, as well as insulin resistance, hyperlipidemia, hyperhomocysteinemia and other pathological mechanisms and hypertension related risk factors. CONCLUSIONS CHM display a beneficial multi-target, multi-component, overall and comprehensive regulation characteristics, and have potential value for clinical application in the treatment of hypertension by regulating the level of oxidative stress.
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Affiliation(s)
- Zixuan Jin
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5 Beixian Ge, Xicheng District, Beijing, 100053, China
| | - Yu Lan
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5 Beixian Ge, Xicheng District, Beijing, 100053, China
| | - Junying Li
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5 Beixian Ge, Xicheng District, Beijing, 100053, China
| | - Pengqian Wang
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Xingjiang Xiong
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5 Beixian Ge, Xicheng District, Beijing, 100053, China.
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Liu Y, Li X, Chen C, Ding N, Ma S, Yang M. Exploration of compatibility rules and discovery of active ingredients in TCM formulas by network pharmacology. CHINESE HERBAL MEDICINES 2024; 16:572-588. [PMID: 39606260 PMCID: PMC11589340 DOI: 10.1016/j.chmed.2023.09.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 08/12/2023] [Accepted: 09/05/2023] [Indexed: 11/29/2024] Open
Abstract
Network pharmacology is an interdisciplinary field that utilizes computer science, technology, and biological networks to investigate the intricate interplay among compounds/ingredients, targets, and diseases. Within the realm of traditional Chinese medicine (TCM), network pharmacology serves as a scientific approach to elucidate the compatibility relationships and underlying mechanisms of action in TCM formulas. It facilitates the identification of potential active ingredients within these formulas, providing a comprehensive understanding of their holistic and systematic nature, which aligns with the holistic principles inherent in TCM theory. TCM formulas exhibit complexity due to their multi-component characteristic, involving diverse targets and pathways. Consequently, investigating their material basis and mechanisms becomes challenging. Network pharmacology has emerged as a valuable approach in TCM formula research, leveraging its holistic and systematic advantages. The manuscript aims to provide an overview of the application of network pharmacology in studying TCM formula compatibility rules and explore future research directions. Specifically, we focus on how network pharmacology aids in interpreting TCM pharmacological theories and understanding formula compositions. Additionally, we elucidate the process of utilizing network pharmacology to identify active ingredients within TCM formulas. These findings not only offer novel research models and perspectives for integrating network pharmacology with TCM theory but also present new methodologies for investigating TCM formula compatibility. All in all, network pharmacology has become an indispensable and crucial tool in advancing TCM formula research.
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Affiliation(s)
- Yishu Liu
- Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Xue Li
- Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Chao Chen
- Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Nan Ding
- Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Shiyu Ma
- Ruijin Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200025, China
| | - Ming Yang
- Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
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Huang J, Shi R, Chen F, Tan HY, Zheng J, Wang N, Li R, Wang Y, Yang T, Feng Y, Zhong Z. Exploring the anti-hepatocellular carcinoma effects of Xianglian Pill: Integrating network pharmacology and RNA sequencing via in silico and in vitro studies. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 133:155905. [PMID: 39128301 DOI: 10.1016/j.phymed.2024.155905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Revised: 05/21/2024] [Accepted: 07/20/2024] [Indexed: 08/13/2024]
Abstract
BACKGROUND Liver cancer represents a most common and fatal cancer worldwide. Xianglian Pill (XLP) is an herbal formula holding great promise in clearing heat for treating diseases in an integrative and holistic way. However, due to the complex constituents and multiple targets, the exact molecular mechanisms of action of XLP are still unclear. PURPOSE This study is focused on hepatocellular carcinoma (HCC), the most common type of liver cancer. The aim of this study is to develop a fast and efficient model to investigate the anti-HCC effects of XLP, and its underlying mechanisms. MATERIALS AND METHODS HepG2, Hep3B, Mahlavu, HuH-7, or Li-7 cells were employed in the studies. The ingredients were analyzed using liquid chromatography tandem mass spectrometry (LC-MS). RNA sequencing combined with network pharmacology was used to elucidate the therapeutic mechanism of XLP in HCC via in silico and in vitro studies. An approach was constructed to improve the accuracy of prediction in network pharmacology by combining big data and omics. RESULTS First, we identified 13 potential ingredients in the serum of XLP-administered rats using LC-MS. Then the network pharmacology was performed to predict that XLP demonstrates anti-HCC effects via targeting 94 genes involving in 13 components. Modifying the database thresholds might impact the accuracy of network pharmacology analysis based on RNA sequencing data. For instance, when the matching rate peak is 0.43, the correctness rate peak is 0.85. Moreover, 9 components of XLP and 6 relevant genes have been verified with CCK-8 and RT-qPCR assay, respectively. CONCLUSION Based on the crossing studies of RNA sequencing and network pharmacology, XLP was found to improve HCC through multiple targets and pathways. Additionally, the study provides a way to optimize network pharmacology analysis in herbal medicine research.
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Affiliation(s)
- Jihan Huang
- Center for Drug Clinical Research, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Ruipeng Shi
- Macao Centre for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR 999078, China
| | - Feiyu Chen
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR 999077, China
| | - Hor Yue Tan
- Centre for Chinese Herbal Medicine Drug Development, Hong Kong Baptist University, Hong Kong SAR 999077, China
| | - Jinbin Zheng
- Macao Centre for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR 999078, China
| | - Ning Wang
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR 999077, China
| | - Ran Li
- Center for Drug Clinical Research, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Yulin Wang
- Center for Drug Clinical Research, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Tao Yang
- Center for Drug Clinical Research, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Yibin Feng
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR 999077, China.
| | - Zhangfeng Zhong
- Macao Centre for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR 999078, China.
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Song Z, Chen G, Chen CYC. AI empowering traditional Chinese medicine? Chem Sci 2024; 15:d4sc04107k. [PMID: 39355231 PMCID: PMC11440359 DOI: 10.1039/d4sc04107k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 09/22/2024] [Indexed: 10/03/2024] Open
Abstract
For centuries, Traditional Chinese Medicine (TCM) has been a prominent treatment method in China, incorporating acupuncture, herbal remedies, massage, and dietary therapy to promote holistic health and healing. TCM has played a major role in drug discovery, with over 60% of small-molecule drugs approved by the FDA from 1981 to 2019 being derived from natural products. However, TCM modernization faces challenges such as data standardization and the complexity of TCM formulations. The establishment of comprehensive TCM databases has significantly improved the efficiency and accuracy of TCM research, enabling easier access to information on TCM ingredients and encouraging interdisciplinary collaborations. These databases have revolutionized TCM research, facilitating advancements in TCM modernization and patient care. In addition, advancements in AI algorithms and database data quality have accelerated progress in AI for TCM. The application of AI in TCM encompasses a wide range of areas, including herbal screening and new drug discovery, diagnostic and treatment principles, pharmacological mechanisms, network pharmacology, and the incorporation of innovative AI technologies. AI also has the potential to enable personalized medicine by identifying patterns and correlations in patient data, leading to more accurate diagnoses and tailored treatments. The potential benefits of AI for TCM are vast and diverse, promising continued progress and innovation in the field.
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Affiliation(s)
- Zhilin Song
- State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School Shenzhen Guangdong 518055 China
- AI for Science (AI4S)-Preferred Program, School of Electronic and Computer Engineering, Peking University Shenzhen Graduate School Shenzhen Guangdong 518055 China
| | - Guanxing Chen
- Artificial Intelligence Medical Research Center, School of Intelligent Systems Engineering, Shenzhen Campus of Sun Yat-sen University Shenzhen Guangdong 518107 China
| | - Calvin Yu-Chian Chen
- State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School Shenzhen Guangdong 518055 China
- AI for Science (AI4S)-Preferred Program, School of Electronic and Computer Engineering, Peking University Shenzhen Graduate School Shenzhen Guangdong 518055 China
- Department of Medical Research, China Medical University Hospital Taichung 40447 Taiwan
- Department of Bioinformatics and Medical Engineering, Asia University Taichung 41354 Taiwan
- Guangdong L-Med Biotechnology Co., Ltd Meizhou Guangdong 514699 China
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Li X, Chen X, Yu H, Huang R, Wu P, Gong Y, Chen X, Liu C. Knockdown and Overexpression Experiments to Investigate the Inhibitory Mechanism of Fuzheng Xiaozheng Prescription, an Effective Chinese Herbal Formula for the Clinical Treatment of Hepatocellular Carcinoma. Pharmaceuticals (Basel) 2024; 17:1159. [PMID: 39338323 PMCID: PMC11434836 DOI: 10.3390/ph17091159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 08/27/2024] [Accepted: 08/28/2024] [Indexed: 09/30/2024] Open
Abstract
Fuzheng Xiaozheng prescription (FZXZP) is an effective formula for the treatment of different kinds of chronic liver diseases. However, its potential molecular mechanisms in treating hepatocellular carcinoma (HCC) have not been investigated thoroughly. The aim of this study is to elucidate the targets and intrinsic mechanisms of FZXZP and their active components for the treatment of HCC. The efficacy of FZXZP against HCC was clarified through a rat HCC model and HCC cell culture. Network pharmacology and molecular docking were utilized to predict the mechanism of action and effector components of FZXZP. The key mechanism and targets were verified by the construction of overexpression and knockout cell models. The results showed that FZXZP greatly delayed the development of HCC in vivo experiments, as evidenced by biochemical evaluations, H&E analyses and growth inhibition of HCC. FZXZP dramatically inhibited cell viability and proliferative capacity and induced the apoptosis of hepatoma cells in vitro. Moreover, network pharmacology analyses demonstrated that the EGFR family and apoptosis-related targets were found to be the most significant in bioinformatics analysis. Furthermore, the EGFR/STAT3 signal axis might be the most likely target of FZXZP in anti-HCC due to the fact that it could be down-regulated by FZXZP with an upward trend of Bax, Caspase-3, Caspase-8, Caspase-9 and an inverse trend of Bcl2. Importantly, the above targeted signal axis was finally validated by our knockdown and overexpression analyses. Meanwhile, flow cytometry and TUNEL staining also revealed that FZXZP significantly induced apoptosis in the EGFR-overexpressing HCC cell line. The molecular docking results revealed that the key effector components of FZXZP that exerted the above regulatory roles were wogonin and glycitein. All of these results suggest that FZXZP could significantly delay HCC development by inhibiting proliferation and promoting apoptosis of HCC cells, and the EGFR/STAT3 signal axis might be a critical signal axis of FZXZP in suppressing HCC progression.
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Affiliation(s)
- Xia Li
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Xiaofeng Chen
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Han Yu
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Renwei Huang
- Sichuan Provincial Key Laboratory for Development and Utilization of Characteristic Horticultural Biological Resources, College of Chemistry and Life Sciences, Chengdu Normal University, Chengdu 611130, China
| | - Peijie Wu
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Yanju Gong
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Xiping Chen
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Chao Liu
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
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Gao K, Cao W, He Z, Liu L, Guo J, Dong L, Song J, Wu Y, Zhao Y. Network medicine analysis for dissecting the therapeutic mechanism of consensus TCM formulae in treating hepatocellular carcinoma with different TCM syndromes. Front Endocrinol (Lausanne) 2024; 15:1373054. [PMID: 39211446 PMCID: PMC11357915 DOI: 10.3389/fendo.2024.1373054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Accepted: 07/26/2024] [Indexed: 09/04/2024] Open
Abstract
Introduction Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality worldwide. Traditional Chinese Medicine (TCM) is widely utilized as an adjunct therapy, improving patient survival and quality of life. TCM categorizes HCC into five distinct syndromes, each treated with specific herbal formulae. However, the molecular mechanisms underlying these treatments remain unclear. Methods We employed a network medicine approach to explore the therapeutic mechanisms of TCM in HCC. By constructing a protein-protein interaction (PPI) network, we integrated genes associated with TCM syndromes and their corresponding herbal formulae. This allowed for a quantitative analysis of the topological and functional relationships between TCM syndromes, HCC, and the specific formulae used for treatment. Results Our findings revealed that genes related to the five TCM syndromes were closely associated with HCC-related genes within the PPI network. The gene sets corresponding to the five TCM formulae exhibited significant proximity to HCC and its related syndromes, suggesting the efficacy of TCM syndrome differentiation and treatment. Additionally, through a random walk algorithm applied to a heterogeneous network, we prioritized active herbal ingredients, with results confirmed by literature. Discussion The identification of these key compounds underscores the potential of network medicine to unravel the complex pharmacological actions of TCM. This study provides a molecular basis for TCM's therapeutic strategies in HCC and highlights specific herbal ingredients as potential leads for drug development and precision medicine.
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Affiliation(s)
- Kai Gao
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Chaoyang District, Beijing, China
| | - WanChen Cao
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Chaoyang District, Beijing, China
| | - ZiHao He
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Chaoyang District, Beijing, China
| | - Liu Liu
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Chaoyang District, Beijing, China
| | - JinCheng Guo
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Chaoyang District, Beijing, China
| | - Lei Dong
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Chaoyang District, Beijing, China
| | - Jini Song
- New York Institute of Technology College of Osteopathic Medicine, Arkansas State University, Jonesboro, AR, United States
| | - Yang Wu
- The Research Center for Ubiquitous Computing Systems (CUbiCS), Institute of Computing Technology, Chinese Academy of Sciences, Beijing, China
| | - Yi Zhao
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Chaoyang District, Beijing, China
- The Research Center for Ubiquitous Computing Systems (CUbiCS), Institute of Computing Technology, Chinese Academy of Sciences, Beijing, China
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11
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Wang ZZ, Wang HL, Xiong W, Du J, Liu R. Traditional Chinese Medicine Erhuang Suppository for Treatment of Persistent High-risk Human Papillomavirus Infection and Its Impact on Transcriptome of Uterine Cervix. Curr Med Sci 2024; 44:841-853. [PMID: 39039373 DOI: 10.1007/s11596-024-2898-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 05/17/2024] [Indexed: 07/24/2024]
Abstract
OBJECTIVE High-risk human papillomavirus (HR-HPV) infection is the chief cause of cervical intraepithelial neoplasia (CIN) and cervical carcinoma. The Erhuang suppository (EHS) is a traditional Chinese medicine (TCM) prepared from realgar (As2S2), Coptidis rhizoma, alumen, and borneolum syntheticum and has been used for antiviral and antitumor purposes. However, whether EHS can efficiently alleviate HR-HPV infection remains unclear. This study was conducted to evaluate the efficacy of EHS for the treatment of persistent HR-HPV infection in the uterine cervix. METHODS In this study, we evaluated the therapeutic efficacy of EHS in a randomized controlled clinical trial with a 3-month follow-up. Totally, 70 patients with persistent HR-HPV infection were randomly assigned to receive intravaginal administration of EHS or placebo. HPV DNA, ThinPrep cytologic test (TCT), colposcopy, and safety evaluation were carried out after treatment. Microarray analysis was performed to compare transcriptome profiles before and after EHS treatment. A K14-HPV16 mouse model was generated to confirm the efficiency of EHS. RESULTS After 3 months, 74.3% (26/35) of the patients in the treatment group were HPV negative, compared to 6.9% (2/29) in the placebo group. High-throughput microarrays revealed distinct transcriptome profiles after treatment. The differentially expressed genes were significantly enriched in complement activation, immune response, and apoptotic processes. The K14-HPV16 mouse model also validated the remarkable efficacy of EHS. CONCLUSION This study demonstrated that EHS is effective against HR-HPV infection and cervical lesions. Additionally, no obvious systemic toxicity was observed in patients during the trial. The superior efficacy and safety of EHS demonstrated its considerable value as a potential cost-effective drug for the treatment of HPV infection and HPV-related cervical diseases.
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Affiliation(s)
- Zi-Zhuo Wang
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Hui-Li Wang
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Wei Xiong
- Department of Pharmacology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Juan Du
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Rong Liu
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
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Lin J, Gu M, Wang X, Chen Y, Chau NV, Li J, Chu Q, Qing L, Wu W. Huanglian Jiedu decoction inhibits vascular smooth muscle cell-derived foam cell formation by activating autophagy via suppressing P2RY12. JOURNAL OF ETHNOPHARMACOLOGY 2024; 328:118125. [PMID: 38561055 DOI: 10.1016/j.jep.2024.118125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 03/12/2024] [Accepted: 03/27/2024] [Indexed: 04/04/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Huanglian Jiedu Decoction (HLJDD) is a Chinese medicine with a long history of therapeutic application. It is widely used in treating atherosclerosis (AS) in Chinese medicine theory and clinical practice. However, the mechanism of HLJDD in treating AS remains unclear. AIM OF THE STUDY To investigate the efficacy and mechanism of HLJDD in treating AS. MATERIALS AND METHODS AS was induced on high-fat diet-fed ApoE-/- mice, with the aorta pathological changes evaluated with lipid content and plaque progression. In vitro, foam cells were induced by subjecting primary mouse aortic vascular smooth muscle cells (VSMCs) to oxLDL incubation. After HLJDD intervention, VSMCs were assessed with lipid stack, apoptosis, oxidative stress, and the expression of foam cell markers. The effects of P2RY12 were tested by adopting clopidogrel hydrogen sulfate (CDL) in vivo and transfecting P2RY12 over-expressive plasmid in vitro. Autophagy was inhibited by Chloroquine or transfecting siRNA targeting ATG7 (siATG7). The mechanism of HLJDD treating atherosclerosis was explored using network pharmacology and validated with molecular docking and co-immunoprecipitation. RESULTS HLJDD exhibited a dose-dependent reduction in lipid deposition, collagen loss, and necrosis within plaques. It also reversed lipid accumulation and down-regulated the expression of foam cell markers. P2RY12 inhibition alleviated AS, while P2RY12 overexpression enhanced foam cell formation and blocked the therapeutic effects of HLJDD. Network pharmacological analysis suggested that HLJDD might mediate PI3K/AKT signaling pathway-induced autophagy. P2RY12 overexpression also impaired autophagy. Similarly, inhibiting autophagy counteracted the effect of CDL, exacerbated AS in vivo, and promoted foam cell formation in vitro. However, HLJDD treatment mitigated these detrimental effects by suppressing the PI3K/AKT signaling pathway. Immunofluorescence and molecular docking revealed a high affinity between P2RY12 and PIK3CB, while co-immunoprecipitation assays illustrated their interaction. CONCLUSIONS HLJDD inhibited AS in vivo and foam cell formation in vitro by restoring P2RY12/PI3K/AKT signaling pathway-suppressed autophagy. This study is the first to reveal an interaction between P2RY12 and PI3K3CB.
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Affiliation(s)
- Jinhai Lin
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, 12 Jichang Road, Guangzhou, 510405, Guangdong, China; Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, 12 Jichang Road, Guangzhou, 510405, Guangdong, China.
| | - Mingyang Gu
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, 12 Jichang Road, Guangzhou, 510405, Guangdong, China.
| | - Xiaolong Wang
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, 12 Jichang Road, Guangzhou, 510405, Guangdong, China.
| | - Yuanyuan Chen
- Qinchengda Community Health Service Center, Shenzhen Bao'an Traditional Chinese Medicine Hospital Group, No. 225, Block 10A, Qinchengda Yueyuan Commercial and Residential Building, Shenzhen, 518100, Guangdong, China.
| | - Nhi Van Chau
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, 12 Jichang Road, Guangzhou, 510405, Guangdong, China; Traditional Medicine Department, Can Tho University of Medicine and Pharmacy, 179 Nguyen Van Cu Street, An Khanh, Ninh Kieu, Can Tho, 94000, Viet Nam.
| | - Junlong Li
- The Department of Cardiology, First Affiliated Hospital, Guangzhou University of Chinese Medicine, 16 Jichang Road, Guangzhou, 510405, Guangdong, China.
| | - Qingmin Chu
- The Department of Cardiology, First Affiliated Hospital, Guangzhou University of Chinese Medicine, 16 Jichang Road, Guangzhou, 510405, Guangdong, China.
| | - Lijin Qing
- The Department of Cardiology, First Affiliated Hospital, Guangzhou University of Chinese Medicine, 16 Jichang Road, Guangzhou, 510405, Guangdong, China.
| | - Wei Wu
- The Department of Cardiology, First Affiliated Hospital, Guangzhou University of Chinese Medicine, 16 Jichang Road, Guangzhou, 510405, Guangdong, China.
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Xie Y, Gong S, Wang L, Yang Z, Yang C, Li G, Zha H, Lv S, Xiao B, Chen X, Di Z, He Q, Wang J, Weng Q. Unraveling the treatment effects of huanglian jiedu decoction on drug-induced liver injury based on network pharmacology, molecular docking and experimental validation. BMC Complement Med Ther 2024; 24:219. [PMID: 38849824 PMCID: PMC11157734 DOI: 10.1186/s12906-024-04517-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Accepted: 05/22/2024] [Indexed: 06/09/2024] Open
Abstract
Huanglian Jiedu Decoction (HJD) is a well-known Traditional Chinese Medicine formula that has been used for liver protection in thousands of years. However, the therapeutic effects and mechanisms of HJD in treating drug-induced liver injury (DILI) remain unknown. In this study, a total of 26 genes related to both HJD and DILI were identified, which are corresponding to a total of 41 potential active compounds in HJD. KEGG analysis revealed that Tryptophan metabolism pathway is particularly important. The overlapped genes from KEGG and GO analysis indicated the significance of CYP1A1, CYP1A2, and CYP1B1. Experimental results confirmed that HJD has a protective effect on DILI through Tryptophan metabolism pathway. In addition, the active ingredients Corymbosin, and Moslosooflavone were found to have relative strong intensity in UPLC-Q-TOF-MS/MS analysis, showing interactions with CYP1A1, CYP1A2, and CYP1B1 through molecule docking. These findings could provide insights into the treatment effects of HJD on DILI.
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Affiliation(s)
- Yaochen Xie
- Center for Drug Safety Evaluation and Research, Zhejiang Province Key Laboratory of Anti- Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310007, China
| | - Shuchen Gong
- Center for Drug Safety Evaluation and Research, Zhejiang Province Key Laboratory of Anti- Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310007, China
- Taizhou Institute of Zhejiang University, Taizhou, 318000, China
- Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
| | - Lingkun Wang
- Center for Drug Safety Evaluation and Research, Zhejiang Province Key Laboratory of Anti- Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310007, China
| | - Zhaoxu Yang
- Center for Drug Safety Evaluation and Research, Zhejiang Province Key Laboratory of Anti- Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310007, China
| | - Chen Yang
- Center for Drug Safety Evaluation and Research, Zhejiang Province Key Laboratory of Anti- Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310007, China
| | - Guilin Li
- Center for Drug Safety Evaluation and Research, Zhejiang Province Key Laboratory of Anti- Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310007, China
| | - Huiyan Zha
- Center for Drug Safety Evaluation and Research, Zhejiang Province Key Laboratory of Anti- Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310007, China
| | - Shuying Lv
- Center for Drug Safety Evaluation and Research, Zhejiang Province Key Laboratory of Anti- Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310007, China
| | - Boneng Xiao
- Center for Drug Safety Evaluation and Research, Zhejiang Province Key Laboratory of Anti- Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310007, China
- Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
| | - Xiaoyu Chen
- Center for Drug Safety Evaluation and Research, Zhejiang Province Key Laboratory of Anti- Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310007, China
| | - Zhenning Di
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Qiaojun He
- Center for Drug Safety Evaluation and Research, Zhejiang Province Key Laboratory of Anti- Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310007, China
- ZJU-Xinchang Joint Innovation Center (TianMu Laboratory), Gaochuang Hi-Tech Park, Xinchang, 312500, Zhejiang, China
- Department of Cardiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310058, Zhejiang, China
| | - Jincheng Wang
- Center for Drug Safety Evaluation and Research, Zhejiang Province Key Laboratory of Anti- Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310007, China.
- Taizhou Institute of Zhejiang University, Taizhou, 318000, China.
- Beijing Life Science Academy, Beijing, 102200, China.
| | - Qinjie Weng
- Center for Drug Safety Evaluation and Research, Zhejiang Province Key Laboratory of Anti- Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310007, China.
- Taizhou Institute of Zhejiang University, Taizhou, 318000, China.
- ZJU-Xinchang Joint Innovation Center (TianMu Laboratory), Gaochuang Hi-Tech Park, Xinchang, 312500, Zhejiang, China.
- The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
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Ren S, Zhou R, Tang Z, Song Z, Li N, Shi X, Liu Y, Chu Y. Wuling capsule modulates macrophage polarization by inhibiting the TLR4-NF-κB signaling pathway to relieve liver fibrosis. Int Immunopharmacol 2024; 129:111598. [PMID: 38309092 DOI: 10.1016/j.intimp.2024.111598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Revised: 01/15/2024] [Accepted: 01/24/2024] [Indexed: 02/05/2024]
Abstract
BACKGROUND AND PURPOSE Wuling capsule (WL) has good efficacy in the clinical treatment of chronic hepatitis B and liver injury. Liver fibrosis is a common pathological feature of chronic liver disease and may progress to irreversible cirrhosis and liver cancer. Accumulating evidence reveals that modulating macrophage polarization contribute to the therapy of liver fibrosis. However, the effects of WL on modulating macrophage polarization to relive liver fibrosis remain unclear. This study investigated the anti-liver fibrosis effects of WL in carbon tetrachloride (CCl4)-induced liver fibrosis in rats, and the modulation effects and underlying molecular mechanism on macrophage polarization. METHODS A rat liver fibrosis model was constructed by intraperitoneal injection of 40 % CCl4 olive oil mixture. At 2, 4, 6, and 8 weeks, the histopathological status of the liver was assessed by hematoxylin-eosin (HE) and Masson staining; the liver biochemical indexes were measured in rat liver tissue. The expression levels of inflammatory cytokines in liver tissue were detected by ELISA. The mRNA levels and proteins expression of macrophage markers of different phenotypes, TLR4-NF-κB signaling pathway indicators were detected independently by ELISA, immunofluorescence, RT-PCR and western blotting. RESULTS In vivo, WL treatment attenuated abnormal changes in weight, organ indices and biochemical indices, alleviated pathological changes, and reduced collagen fiber deposition as well as the expression of α-SMA in liver tissues. Further studies revealed that WL decreased the expression of the macrophage M1 polarization markers inducible nitric oxide synthase (iNOS), TNF-α, IL-6, and CD86, promoted the expression of the M2 macrophage polarization markers IL-10, CD206, and arginase-1 (Arg-1), and inhibited the activation of the TLR4-NF-κB signaling pathway via several key signaling proteins. In vitro, WL significantly suppressed macrophage M1 polarization, and promoted M2 polarization while boosted M1 polarization transform to M2 polarization in LPS-activated RAW264.7 cells. CONCLUSIONS This study demonstrated that WL modulated macrophage polarization against liver fibrosis mainly by inhibiting the activation of the TLR4-NF-κB signaling pathway.
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Affiliation(s)
- Sujuan Ren
- Co-Construction Collaborative Innovation Center for Chinese Medicine Resources Industrialization by Shaanxi and Education Ministry, Shaanxi Innovative Drug Research Center, State Key Laboratory of Research and Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi University of Chinese Medicine, Xianyang 712000, China
| | - Rui Zhou
- Co-Construction Collaborative Innovation Center for Chinese Medicine Resources Industrialization by Shaanxi and Education Ministry, Shaanxi Innovative Drug Research Center, State Key Laboratory of Research and Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi University of Chinese Medicine, Xianyang 712000, China.
| | - Zhishu Tang
- Co-Construction Collaborative Innovation Center for Chinese Medicine Resources Industrialization by Shaanxi and Education Ministry, Shaanxi Innovative Drug Research Center, State Key Laboratory of Research and Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi University of Chinese Medicine, Xianyang 712000, China; China Academy of Chinese Medical Sciences, Beijing 100029, China.
| | - Zhongxing Song
- Co-Construction Collaborative Innovation Center for Chinese Medicine Resources Industrialization by Shaanxi and Education Ministry, Shaanxi Innovative Drug Research Center, State Key Laboratory of Research and Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi University of Chinese Medicine, Xianyang 712000, China
| | - Nan Li
- Co-Construction Collaborative Innovation Center for Chinese Medicine Resources Industrialization by Shaanxi and Education Ministry, Shaanxi Innovative Drug Research Center, State Key Laboratory of Research and Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi University of Chinese Medicine, Xianyang 712000, China
| | - Xinbo Shi
- Co-Construction Collaborative Innovation Center for Chinese Medicine Resources Industrialization by Shaanxi and Education Ministry, Shaanxi Innovative Drug Research Center, State Key Laboratory of Research and Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi University of Chinese Medicine, Xianyang 712000, China
| | - Yanru Liu
- Co-Construction Collaborative Innovation Center for Chinese Medicine Resources Industrialization by Shaanxi and Education Ministry, Shaanxi Innovative Drug Research Center, State Key Laboratory of Research and Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi University of Chinese Medicine, Xianyang 712000, China
| | - Yajun Chu
- Tsing Hua De Ren Xi'an Happiness Pharmaceutical Co., Ltd., Xi'an 710000, China
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15
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Luo J, Chen QX, Li P, Yu H, Yu L, Lu JL, Yin HZ, Huang BJ, Zhang SJ. Lobelia chinensis Lour inhibits the progression of hepatocellular carcinoma via the regulation of the PTEN/AKT signaling pathway in vivo and in vitro. JOURNAL OF ETHNOPHARMACOLOGY 2024; 318:116886. [PMID: 37429502 DOI: 10.1016/j.jep.2023.116886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 07/05/2023] [Accepted: 07/07/2023] [Indexed: 07/12/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Lobelia chinensis Lour. (LCL) is a common herb used for clearing heat and detoxifying, and it has antitumor activity. Quercetin is one of its important components, which may play an important role in the treatment of hepatocellular carcinoma (HCC). AIM OF THE STUDY To study the active ingredients of LCL, their mechanism of action on HCC, and lay the foundations for the development of new drugs for the treatment of HCC. MATERIALS AND METHODS Network pharmacology was used to examine the probable active ingredients and mechanisms of action of LCL in HCC treatment. Based on an oral bioavailability of ≥30% and a drug-likeness index of ≥0.18, relevant compounds were selected from the Traditional Chinese Medicine Systems Pharmacology database and TCM Database@Taiwan. HCC-related targets were identified using gene cards and the Online Mendelian Inheritance in Man (OMIM) database. A Venn diagram was created to assess the relationship between the intersection of disease and medication targets by creating a protein-protein interaction network, and the hub targets were selected by topology. Gene Ontology enrichment analyses were performed using the DAVID tool. Finally, in vivo and in vitro experiments (qRT-PCR, western blotting, hematoxylin and eosin staining, transwell assays, scratch tests, and flow cytometry assays) verified that LCL demonstrated notable therapeutic effects on HCC. RESULTS In total, 16 bioactive LCL compounds met the screening criteria. The 30 most important LCL therapeutic target genes were identified. Of these, AKT1 and MAPK1 were the most important target genes, and the AKT signaling pathway was identified as the key pathway. Transwell and scratch assays showed that LCL prevented cell migration, and flow cytometry tests revealed that the LCL-treated group showed a considerably higher rate of apoptosis than the control group. LCL reduced tumor formation in mice in vivo, and Western blot analysis of tumor tissues treated with LCL indicated variations in PTEN, p-MAPK and p-AKT1 levels. The results show that LCL may inhibit the progression of HCC through the PTEN/AKT signaling pathway to achieve the goal of treating HCC. CONCLUSION LCL is a broad-spectrum anticancer agent. These findings reveal potential treatment targets and strategies for preventing the spread of cancer, which could aid in screening potential traditional Chinese medicine for anticancer and clarifying their mechanisms.
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Affiliation(s)
- Jin Luo
- The First Affiliated Hospital of Sun Yat-sen, Department of Traditional Chinese Medicine, Guangzhou, 510800, China; Shenzhen Children's Hospital, Futian District, Shenzhen, 518000, Guangdong, PR China
| | - Qiu-Xia Chen
- The First Affiliated Hospital of Sun Yat-sen, Department of Traditional Chinese Medicine, Guangzhou, 510800, China
| | - Pan Li
- Department of Radiotherapy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450003, China
| | - He Yu
- The First Affiliated Hospital of Sun Yat-sen, Department of Traditional Chinese Medicine, Guangzhou, 510800, China
| | - Ling Yu
- The First Affiliated Hospital of Sun Yat-sen, Department of Traditional Chinese Medicine, Guangzhou, 510800, China
| | - Jia-Li Lu
- Department of General Practice, Shenzhen Longgang Fourth People's Hospital, Shenzhen, 518100, China
| | - Hong-Zhi Yin
- Department of Pediatrics, Beijing University of Chinese Medicine Shenzhen Hospital (Longgang), Shenzhen, 518100, China
| | - Bi-Jun Huang
- State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
| | - Shi-Jun Zhang
- The First Affiliated Hospital of Sun Yat-sen, Department of Traditional Chinese Medicine, Guangzhou, 510800, China.
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Dong Md S, Xu Md P, Yang Md P, Jiao Md J, Cheng Md PhD CS, Chen Md PhD L. "Huanglianjiedu Decoction" Against Pancreatic Adenocarcinoma Proliferation of by Downregulating the PI3K/AKT/mTOR and MAPK/ERK1/2 Signaling Pathways. J Evid Based Integr Med 2024; 29:2515690X241291381. [PMID: 39410848 PMCID: PMC11489918 DOI: 10.1177/2515690x241291381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2024] Open
Abstract
BACKGROUND Huanglianjiedu decoction (HLJDD) is a classical Traditional Chinese Medicine (TCM) prescription with thousand years of clinical use against various malignancies, including pancreatic adenocarcinoma (PAAD). However, its potential bioactive component and molecular mechanism remains unclear. AIMS This study is to inspect the HLJDD mechanisms of action against PAAD via integrated computational and pharmacochemistry strategy, in vivo and in vitro experiments to validate associated targets and pathways. METHODS A PAAD xenograft model was established by subcutaneous injecting Panc02 cells into C57BL/6 mice. Ultra-high performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) was engaged to determine constituents of HLJDD and assessed for pharmacokinetic scheme using the TCM Systems Pharmacology Platform (TCM-SP). Differentially expressed genes (DEGs) of PAAD was retrieved from the transcriptome dataset GSE43795, followed by recognizing overlapping targets the oncogenes and target genes of PAAD and HLJDD, respectively. Putative signaling pathways of HLJDD in treating PAAD were enriched using KEGG and GO analyses. The anti-PAAD effects of HLJDD was assessed in vivo and in vitro, besides, the potential mechanism was validated using immunoblotting and immunohistochemical assays. RESULTS HLJDD significantly suppressed the growth of transplanted PAAD tumors, constrained PAAD progression, and induced apoptosis and S-phase arrest. Seventy-five active components meeting the drug-likeness criteria and 278 target genes of HLJDD were identified. KEGG analysis indicated that the top three enriched pathways were cancer, AGE-RAGE signaling, and IL-17 signaling pathways. Disease enrichment analysis highlighted immune, pharmacological, and cancer-related diseases as the top three categories. A total of 47 potential target genes were identified. Immunoblotting revealed that HLJDD inhibited PI3K and MAPK-related signaling pathways, while immunohistochemical staining confirmed that HLJDD suppressed the expression of phosphorylated MAPK and ERK1/2. CONCLUSION HLJDD inhibited PAAD in vitro and in vivo via the modulation of multiple mechanisms, including regulation of PI3K/AKT/mTOR and MAPK/ERK1/2 signaling pathways.
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Affiliation(s)
- Shu Dong Md
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Panling Xu Md
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Chinese Integrative Medicine Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Peiwen Yang Md
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Juying Jiao Md
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Chien-Shan Cheng Md PhD
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Department of Traditional Chinese Medicine, Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital, Shanghai, China
| | - Lianyu Chen Md PhD
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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Hu Y, Xiao Y, Wan L, Wen Z. Network Pharmacology to Reveal the Mechanism of Fufang Banmao Capsule for Treating Unresectable Primary Liver Cancer and Clinical Data Validation. Curr Pharm Des 2024; 30:2785-2796. [PMID: 39092733 DOI: 10.2174/0113816128322791240722064234] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Revised: 06/16/2024] [Accepted: 06/19/2024] [Indexed: 08/04/2024]
Abstract
INTRODUCTION Fufang Banmao capsule (FFBM), a traditional Chinese medicine, has been used to treat primary liver cancer (PLC) for several years. However, the bioactive ingredients, and mechanism of FFBM for treating PLC remains unclear. Our objective is to utilize network pharmacology to investigate these aspects and subsequently validate their effectiveness through clinical data. MATERIALS AND METHODS The FFBM ingredients were obtained from the HERB database and screened for bioactive ingredients using the SwissTargetPrediction database. The PharmMapper and GEO database were used to acquire targets and differentially expressed genes (DEGs) for FFBM and PLC, respectively. Common targets were identified using Venn diagrams, followed by enrichment and protein-protein interaction (PPI) analysis. Furthermore, the Cytoscape software was utilized to identify Hub genes and construct the ingredienttarget- pathway network. Subsequently, patients diagnosed with unresectable PLC who underwent transcatheter arterial chemoembolization (TACE) at our hospital between January 2008 and December 2019 were retrospectively collected. Finally, Cox analysis was conducted to reveal the role of FFBM in the treatment of unresectable PLC. RESULTS FFBM had 232 targets, and PLC had 1582 DEGs. HSP90AA1 and SRC were identified as crucial targets. Alpha-santalol, glycyrrhizin, and morroniside were identified as the top three bioactive ingredients. Enrichment analysis revealed a significant connection between FFBM utilization for treating PLC and multiple pathways, such as chemical carcinogenesis, PI3K-AKT, Rap1, FoxO, MAPK, and VEGF pathway. Clinical data revealed that consuming FFBM significantly improved the prognosis of unresectable PLC with a hazard ratio of 0.69. CONCLUSION Our study identified the bioactive ingredients of FFBM and its potential mechanisms for treating PLC. Additionally, we validated the effectiveness through clinical data.
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Affiliation(s)
- Youwen Hu
- Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Yangyang Xiao
- Department of Gerontology, Jiangxi University of Traditional Chinese Medicine Affiliated Hospital, Nanchang, Jiangxi Province, China
| | - Lijun Wan
- Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Zhili Wen
- Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
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18
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Xiao B, Li J, Qiao Z, Yang S, Kwan HY, Jiang T, Zhang M, Xia Q, Liu Z, Su T. Therapeutic effects of Siegesbeckia orientalis L. and its active compound luteolin in rheumatoid arthritis: network pharmacology, molecular docking and experimental validation. JOURNAL OF ETHNOPHARMACOLOGY 2023; 317:116852. [PMID: 37390879 DOI: 10.1016/j.jep.2023.116852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Revised: 04/19/2023] [Accepted: 06/26/2023] [Indexed: 07/02/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Rheumatoid arthritis (RA) is a common difficult disease with a high disability rate. Siegesbeckia orientalis L. (SO), a Chinese medicinal herb that is commonly used for treating RA in clinical practice. While, the anti-RA effect and the mechanisms of action of SO, as well as its active compound(s) have not been elucidated clearly. AIM OF THE STUDY We aim to explore the molecular mechanism of SO against RA by using network pharmacology analysis, as well as the in vitro and in vivo experimental validations, and to explore the potential bioactive compound(s) in SO. METHODS Network pharmacology is an advanced technology that provides us an efficient way to study the therapeutic actions of herbs with the underlying mechanisms of action delineated. Here, we used this approach to explore the anti-RA effects of SO, and then the molecular biological approaches were used to verify the prediction. We first established a drug-ingredient-target-disease network and a protein-protein interaction (PPI) network of SO-related RA targets, followed by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Further, we used lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and vascular endothelial growth factor-A (VEGFA)-induced human umbilical vein endothelial cell (HUVEC) models, as well as adjuvant-induced arthritis (AIA) rat model to validate the anti-RA effects of SO. The chemical profile of SO was also determined by using the UHPLC-TOF-MS/MS analysis. RESULTS Network pharmacology analysis highlighted inflammatory- and angiogenesis-related signaling pathways as promising pathways that mediate the anti-RA effects of SO. Further, in both in vivo and in vitro models, we found that the anti-RA effect of SO is at least partially due to the inhibition of toll like receptor 4 (TLR4) signaling. Molecular docking analysis revealed that luteolin, an active compound in SO, shows the highest degree of connections in compound-target network; moreover, it has a direct binding to the TLR4/MD-2 complex, which is confirmed in cell models. Besides, more than forty compounds including luteolin, darutoside and kaempferol corresponding to their individual peaks were identified tentatively via matching with the empirical molecular formulae and their mass fragments. CONCLUSION We found that SO and its active compound luteolin exhibit anti-RA activities and potently inhibit TLR4 signaling both in vitro and in vivo. These findings not only indicate the advantage of network pharmacology in the discovery of herb-based therapeutics for treating diseases, but also suggest that SO and its active compound(s) could be developed as potential anti-RA therapeutic drugs.
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Affiliation(s)
- Bixia Xiao
- International Institute for Translational Chinese Medicine, School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
| | - Junmao Li
- School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.
| | - Zhiping Qiao
- International Institute for Translational Chinese Medicine, School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
| | - Songhong Yang
- School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.
| | - Hiu-Yee Kwan
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China; Institute for Research and Continuing Education, Hong Kong Baptist University, Shenzhen, China.
| | - Ting Jiang
- International Institute for Translational Chinese Medicine, School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
| | - Mi Zhang
- International Institute for Translational Chinese Medicine, School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
| | - Quan Xia
- International Institute for Translational Chinese Medicine, School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
| | - Zhongqiu Liu
- International Institute for Translational Chinese Medicine, School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
| | - Tao Su
- International Institute for Translational Chinese Medicine, School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
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Zhang C, Xiang H, Wang J, Shao G, Ding P, Gao Y, Xu H, Ji G, Wu T. Exploring the mechanism of Jianpi Huatan recipe in protecting hepatocellular carcinoma based on network pharmacology. JOURNAL OF ETHNOPHARMACOLOGY 2023; 317:116676. [PMID: 37279814 DOI: 10.1016/j.jep.2023.116676] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 05/08/2023] [Accepted: 05/21/2023] [Indexed: 06/08/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Jianpi Huatan Recipe (JPHTR) is an effective prescription for delaying progression of hepatocellular carcinoma (HCC) provided by Longhua Hospital affiliated to Shanghai University of traditional Chinese Medicine, and it is consisted of nine traditional Chinese drugs, but the protective mechanism of JPHTR against HCC progression is unclear. AIM OF THE STUDY To study the mechanism of JPHTR preventing the progression of HCC based on the network pharmacology. MATERIALS AND METHODS The chemical component and potential gene targets of JPHTR and the important gene targets of HCC were obtained by retrieving traditional Chinese medicine network pharmacology analysis system (TCMNPAS) database. The data obtained from the database are used to construct the drugs-chemical component-targets network and protein-protein interaction network by using Cytoscape software and STRING database. The potential targets of JPHTR and HCC targets were imported into TCMNPAS-related modules in order to obtain the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment pathways. Finally, we used HCC rat model to verify the vital signaling pathways predicted by network pharmacology. RESULTS A total of 197 potential compounds and 721 potential targets of JPHTR and 611 important gene targets of HCC were obtained. Through the experiment in vivo, it was found that JPHTR can reduce the serum levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase, reduce the lipid droplets and inflammatory injury of liver tissue, and reduce the mRNA expression of Interleukin-6 (Il-6), Janus tyrosine Kinase2 (Jak2) and Forkhead box O3 (Foxo3) in FOXO pathway in the liver, thus delaying the development of HCC. CONCLUSION Through network pharmacology and rat experiments, it is preliminarily confirmed that JPHTR may delay the progression of HCC by regulating the expression of Il-6/Jak2/Foxo3 in FOXO signal pathway, which is expected to be a new therapeutic target for the protection of HCC.
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Affiliation(s)
- Caiyun Zhang
- Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Hongjiao Xiang
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Junmin Wang
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Gaoxuan Shao
- Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
| | - Peilun Ding
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Ying Gao
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Hanchen Xu
- Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
| | - Guang Ji
- Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
| | - Tao Wu
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
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Zhu Z, Liu Y, Zeng J, Ren S, Wei L, Wang F, Sun X, Huang Y, Jiang H, Sui X, Jin W, Jin L, Sun X. Diosbulbin C, a novel active ingredient in Dioscorea bulbifera L. extract, inhibits lung cancer cell proliferation by inducing G0/G1 phase cell cycle arrest. BMC Complement Med Ther 2023; 23:436. [PMID: 38049779 PMCID: PMC10694954 DOI: 10.1186/s12906-023-04245-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 11/03/2023] [Indexed: 12/06/2023] Open
Abstract
BACKGROUND Despite the critical progress of non-small cell lung cancer (NSCLC) therapeutic approaches, the clinical outcomes remain considerably poor. The requirement of developing novel therapeutic interventions is still urgent. In this study, we showed for the first time that diosbulbin C, a natural diterpene lactone component extracted from traditional Chinese medicine Dioscorea bulbifera L., possesses high anticancer activity in NSCLC. METHODS A549 and NCI-H1299 cells were used. The inhibitory effects of the diosbulbin C on NSCLC cell proliferation were evaluated using cytotoxicity, clone formation, EdU assay, and flow cytometry. Network pharmacology methods were used to explore the targets through which the diosbulbin C inhibited NSCLC cell proliferation. Molecular docking, qRT-PCR, and western blotting were used to validate the molecular targets and regulated molecules of diosbulbin C in NSCLC. RESULTS Diosbulbin C treatment in NSCLC cells results in a remarkable reduction in cell proliferation and induces significant G0/G1 phase cell cycle arrest. AKT1, DHFR, and TYMS were identified as the potential targets of diosbulbin C. Diosbulbin C may inhibit NSCLC cell proliferation by downregulating the expression/activation of AKT, DHFR, and TYMS. In addition, diosbulbin C was predicted to exhibit high drug-likeness properties with good water solubility and intestinal absorption, highlighting its potential value in the discovery and development of anti-lung cancer drugs. CONCLUSIONS Diosbulbin C induces cell cycle arrest and inhibits the proliferation of NSCLC cells, possibly by downregulating the expression/activation of AKT, DHFR, and TYMS.
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Affiliation(s)
- Zhiyu Zhu
- School of Pharmacy, Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China
| | - Yanfen Liu
- School of Pharmacy, Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China
| | - Jiangping Zeng
- School of Pharmacy, Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China
| | - Shuyi Ren
- School of Pharmacy, Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China
| | - Lu Wei
- School of Pharmacy, Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China
| | - Fei Wang
- School of Pharmacy, Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China
| | - Xiaoyu Sun
- School of Pharmacy, Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China
| | - Yufei Huang
- School of Pharmacy, Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China
| | - Haiyang Jiang
- School of Pharmacy, Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China
| | - Xinbing Sui
- School of Pharmacy, Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China
- Department of Gastrointestinal and Pancreatic Surgery, Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, Zhejiang, China
| | - Weiwei Jin
- Department of Gastrointestinal and Pancreatic Surgery, Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, Zhejiang, China.
| | - Lijun Jin
- Department of Traditional Chinese Medicine, Hangzhou Shangcheng District People's Hospital, Hangzhou, China.
| | - Xueni Sun
- School of Pharmacy, Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China.
- Department of Gastrointestinal and Pancreatic Surgery, Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, Zhejiang, China.
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Park MN. Therapeutic Strategies for Pancreatic-Cancer-Related Type 2 Diabetes Centered around Natural Products. Int J Mol Sci 2023; 24:15906. [PMID: 37958889 PMCID: PMC10648679 DOI: 10.3390/ijms242115906] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 10/23/2023] [Accepted: 10/30/2023] [Indexed: 11/15/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC), a highly malignant neoplasm, is classified as one of the most severe and devastating types of cancer. PDAC is a notable malignancy that exhibits a discouraging prognosis and a rising occurrence. The interplay between diabetes and pancreatic cancer exhibits a reciprocal causation. The identified metabolic disorder has been observed to possess noteworthy consequences on health outcomes, resulting in elevated rates of morbidity. The principal mechanisms involve the suppression of the immune system, the activation of pancreatic stellate cells (PSCs), and the onset of systemic metabolic disease caused by dysfunction of the islets. From this point forward, it is important to recognize that pancreatic-cancer-related diabetes (PCRD) has the ability to increase the likelihood of developing pancreatic cancer. This highlights the complex relationship that exists between these two physiological states. Therefore, we investigated into the complex domain of PSCs, elucidating their intricate signaling pathways and the profound influence of chemokines on their behavior and final outcome. In order to surmount the obstacle of drug resistance and eliminate PDAC, researchers have undertaken extensive efforts to explore and cultivate novel natural compounds of the next generation. Additional investigation is necessary in order to comprehensively comprehend the effect of PCRD-mediated apoptosis on the progression and onset of PDAC through the utilization of natural compounds. This study aims to examine the potential anticancer properties of natural compounds in individuals with diabetes who are undergoing chemotherapy, targeted therapy, or immunotherapy. It is anticipated that these compounds will exhibit increased potency and possess enhanced pharmacological benefits. According to our research findings, it is indicated that naturally derived chemical compounds hold potential in the development of PDAC therapies that are both safe and efficacious.
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Affiliation(s)
- Moon Nyeo Park
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Hoegidong Dongdaemungu, Seoul 05253, Republic of Korea
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22
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Wang H, Chen W, Cui Y, Gong H, Tang A. Anhydroicaritin suppresses tumor progression via the PI3K/AKT signaling pathway in hepatocellular carcinoma. Aging (Albany NY) 2023; 15:7831-7843. [PMID: 37556351 PMCID: PMC10457047 DOI: 10.18632/aging.204948] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 07/14/2023] [Indexed: 08/11/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the most malignant tumors. The in vitro experiments on the application of Anhydroicaritin (AHI), the active ingredient of Bushen Huayu Decoction, in HCC treatment remain limited, particularly regarding its molecular mechanism. METHODS The TCMSP platform was used for drug ingredient screening. The GeneCards database and DisGeNET database are used to collect liver cancer targets. PPI network construction of active component-target intersection target was completed with string database. The GO and KEGG pathway analyses were performed via bioinformatics analysis. The molecular docking was used to confirm AHI's target proteins. The in vitro experiments were performed to validate the effect of AHI on HCC cell and explore the molecular mechanism by western blotting analysis. RESULTS Through the intersection, 155 intersection targets are finally obtained. The top 15 active ingredients were quercetin, kaempferol, beta-sitosterol, luteolin, beta-carotene, Stigmasterol, naringenin, formononetin, baicalein, Anhydroicaritin, isorhamnetin, licochalcone, 7-O-methylisomucronulatol, aloe-emodin and 8-O-Methylreyusi. The molecular mocking analysis showed that the four active components (quercetin, kaempferol, luteolin and AHI) and targets had a good binding activity (affinity ≤ 5 kcal/mol). In vitro experiments reveled that AHI could suppress tumor proliferation, invasion and metastasis of HCC cells. Further analysis showed that AHI inhibited tumor growth by PI3K/AKT signal pathway in HCC. CONCLUSIONS The Bushen Huayu Decoction and its active ingredient AHI could fight HCC. The potential mechanism may be associated with inhibiting the activation of PI3K/AKT signal pathway, which may serve as a potential treatment for HCC therapy.
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Affiliation(s)
- Houhong Wang
- Department of General Surgery, The Affiliated Bozhou Hospital of Anhui Medical University, Bozhou 236800, Anhui, China
| | - Wenli Chen
- Department of General Surgery, The Affiliated Bozhou Hospital of Anhui Medical University, Bozhou 236800, Anhui, China
| | - Yayun Cui
- Department of Cancer Radiotherapy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (Anhui Provincial Cancer Hospital), Hefei 230031, Anhui, China
| | - Huihui Gong
- Faculty of Health and Life Sciences, Oxford Brookes University, Oxford OX3 0BP, United Kingdom
| | - Amao Tang
- Department of Gastroenterology, The Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
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Wang W, Zhang Y, Jiang Y, Wang Y, Zhu J, Wang C, Han X, Wang J. Exploration of potential mechanism of Rougan formula against hepatic fibrosis by network analysis and experimental assessment. JOURNAL OF ETHNOPHARMACOLOGY 2023; 304:115960. [PMID: 36565772 DOI: 10.1016/j.jep.2022.115960] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 11/04/2022] [Accepted: 11/18/2022] [Indexed: 06/17/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Rougan Formula (RG) has long been clinically applied to treat hepatic fibrosis in patients with different chronic liver diseases. However, the core active substances and the potential pharmacological mechanisms of RG remain unclear. AIM OF THE STUDY The purpose of this study is to explore bioactive components, key targets, and potential mechanisms of RG by performing network pharmacological analyses and experimental model validation. MATERIALS AND METHODS All chemical components in RG extract were identified using ultraperformance liquid chromatography-quadrupole/time-of-flight tandem mass technology. The candidate components and drug targets of RG, as well as disease-related genes, were extracted from TCMSP and GeneCards databases. The potential pathways related to genes were predicted by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. The core bioactive components, key targets, and signaling pathways were ultimately obtained by analyzing protein-protein interaction (PPI) and component-target-pathway (C-T-P) networks. Subsequently, the efficacy and underlying mechanisms of RG on hepatic fibrosis were experimentally validated in transforming growth factor-beta 1 (TGF-β1)-induced hepatic stellate cell activation model and CCL4-induced hepatic fibrosis mouse model. RESULTS A total of 52 components in RG extract were obtained, and 22 of them were selected as the core bioactive components. Five hundred and thirty-nine overlapped targets were determined by matching drug targets with disease-related targets. The results of PPI and C-T-P network analyses revealed 100 key targets and 19 signaling pathways associated with RG efficacy. In vitro and in vivo studies further verified that RG exerted a significant anti-hepatic fibrotic effect by suppressing the activation of hepatic stellate cells by downregulating the TGF-β1/Smads signaling pathway. CONCLUSIONS These results may provide some evidence for further clinical research and development of RG formula as an effective and safe drug for hepatic fibrosis treatment.
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Affiliation(s)
- Wenyi Wang
- Department of Liver Disease, Shanghai Yueyang Integrated Traditional Chinese Medicine and Western Medicine Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China; Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
| | - Yu Zhang
- Department of Liver Disease, Shanghai Yueyang Integrated Traditional Chinese Medicine and Western Medicine Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
| | - Yue Jiang
- Engineering Research Center of Modernization of Traditional Chinese Medicine, East China University of Science and Technology, Shanghai, China.
| | - Yujie Wang
- Department of Liver Disease, Shanghai Yueyang Integrated Traditional Chinese Medicine and Western Medicine Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
| | - Junfeng Zhu
- Department of Liver Disease, Shanghai Yueyang Integrated Traditional Chinese Medicine and Western Medicine Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
| | - Chunli Wang
- Engineering Research Center of Modernization of Traditional Chinese Medicine, East China University of Science and Technology, Shanghai, China.
| | - Xianghui Han
- Institute of Chinese Traditional Surgery, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
| | - Jianyi Wang
- Department of Liver Disease, Shanghai Yueyang Integrated Traditional Chinese Medicine and Western Medicine Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
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Chemical Influence of Scutellaria baicalensis—Coptis chinensis Pair on the Extraction Efficiencies of Flavonoids and Alkaloids at Different Extraction Times and Temperatures. SEPARATIONS 2023. [DOI: 10.3390/separations10020131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/17/2023] Open
Abstract
The Scutellaria baicalensis—Coptis chinensis pair is an herbal combination used for the treatment of various heat-related diseases. During the extraction process, two herbs can mutually influence the extraction efficiency of the chemical constituents contained in each herb. The concentrations of five flavonoids from S. baicalensis and seven alkaloids from C. chinensis were compared in paired or single hot-water extracts at different temperatures (80, 90, and 100 °C) and extraction times (60, 90, and 120 min). Temperature- and time-dependent increases in marker compound concentrations were observed in both paired and single extracts, with the exception of baicalin, berberine, and coptisine in the paired extracts at 100 °C. However, the extractions of the compounds in the paired and single extracts were affected differently by the extraction conditions. Furthermore, the concentrations of most marker compounds in single extracts were 1.09–44.13 times those in paired extracts. The contents of baicalin, wogonoside, coptisine, and berberine, known to be easily aggregated by the flavonoid–alkaloid complex, were changed by 0.024–0.764-fold in the paired extract. The effect of extraction temperature and time on the formation of the flavonoid–alkaloid complex was not significant. The extraction efficiency of the flavonoids and alkaloids can be affected by the pair of S. baicalensis—C. chinensis, which is a primary factor in the chemical modification of two herb-containing herbal extracts.
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Zhang C, Chen G, Tang G, Xu X, Feng Z, Lu Y, Chan YT, Wu J, Chen Y, Xu L, Ren Q, Yuan H, Yang DH, Chen ZS, Wang N, Feng Y. Multi-component Chinese medicine formulas for drug discovery: State of the art and future perspectives. ACTA MATERIA MEDICA 2023; 2. [DOI: 10.15212/amm-2022-0049] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/03/2025]
Abstract
For hundreds of years, the drug discovery and development industry has aimed at identifying single components with a clear mechanism of action as desirable candidates for potential drugs. However, this conventional strategy of drug discovery and development has faced challenges including a low success rate and high development costs. Herein, we critically review state-of-the-art drug discovery and development based on multi-component Chinese medicine formulas. We review the policies and application status of new drugs based on multi-component Chinese medicines in the US, China, and the European Union. Moreover, we illustrate several excellent cases of ongoing applications. Biomedical technologies that may facilitate drug discovery and development based on multi-component Chinese medicine formulas are discussed, including network pharmacology, integrative omics, CRISPR gene editing, and chemometrics. Finally, we discuss potential problems and solutions in pre-clinical and clinical research in drug discovery and development based on multi-component Chinese medicine formulas. We hope that this review will promote discussion of the roles of multi-component Chinese medicine formulas in the discovery and development of new drugs for the treatment of human diseases.
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Xia T, Liang X, Liu CS, Hu YN, Luo ZY, Tan XM. Network Pharmacology Integrated with Transcriptomics Analysis Reveals Ermiao Wan Alleviates Atopic Dermatitis via Suppressing MAPK and Activating the EGFR/AKT Signaling. Drug Des Devel Ther 2022; 16:4325-4341. [PMID: 36578822 PMCID: PMC9790806 DOI: 10.2147/dddt.s384927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 12/08/2022] [Indexed: 12/24/2022] Open
Abstract
Background Ermiao Wan (EMW) is commonly used to treat atopic dermatitis (AD) in China. However, the pharmacological mechanisms underlying the action of EMW against AD remain unclear. Purpose We aimed to determine the mechanisms underlying the effectiveness of EMW in the treatment of AD. Methods We evaluated the effect of EMW on AD induced by dinitrochlorobenzene (DNCB) in BALB/C mice. To clarify the key components of EMW in AD treatment, the main components of EMW were identified using HPLC. Serum pharmacochemistry was used to analyze the absorbed ingredients from blood. Based on the phytochemical results, network pharmacology and molecular docking were used to predict the action of EMW. Skin transcriptomic analysis was used to validate the network pharmacology results. RT-qPCR,ELISA, and immunohistochemical were performed to validate the results of skin transcriptomics. Results EMW improved the symptoms of AD, with less rashes, less spontaneous scratching, less inflammatory cell infiltration, and fewer allergic reactions. The established HPLC method is simple and reliable. Chlorogenic acid, phellodendrine, magnoflorine, jatrorrhizine, palmatine, berberine, and atractylodin were the key effective ingredients with a high blood concentration. Fifty-seven primary causal targets of EMW against AD were identified. These targets are mainly involved in ErbB signaling pathways including EGFR, AKT1, MAPK8, JUN, MAPK1. Molecular docking showed that EGFR, AKT1, MAPK8, JUN, MAPK1 had good binding force with EMW. In AD mice, EMW regulated the EGFR/AKT signaling through upregulation of Grb2, GAB1, Raf-1, EGFR, and AKT, and downregulation of MAPK1 and JUN, compared to that in the MD group. Conclusion EMW could alleviate AD through activating EGFR/AKT signaling and suppressing MAPK. This study provides a theoretical basis for the clinical use of EMW.
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Affiliation(s)
- Ting Xia
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China,Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou, 510515, People’s Republic of China,Guangdong Provincial Engineering Laboratory of Chinese Medicine Preparation Technology, Guangzhou, 510515, People’s Republic of China
| | - Xiao Liang
- School of Pharmaceutical Sciences, Guilin Medical University, Guilin, 541199, People’s Republic of China
| | - Chang-Shun Liu
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China,Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou, 510515, People’s Republic of China,Guangdong Provincial Engineering Laboratory of Chinese Medicine Preparation Technology, Guangzhou, 510515, People’s Republic of China
| | - Yan-Nan Hu
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China,Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou, 510515, People’s Republic of China,Guangdong Provincial Engineering Laboratory of Chinese Medicine Preparation Technology, Guangzhou, 510515, People’s Republic of China
| | - Zhen-Ye Luo
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China,Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou, 510515, People’s Republic of China,Guangdong Provincial Engineering Laboratory of Chinese Medicine Preparation Technology, Guangzhou, 510515, People’s Republic of China
| | - Xiao-Mei Tan
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China,Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou, 510515, People’s Republic of China,Guangdong Provincial Engineering Laboratory of Chinese Medicine Preparation Technology, Guangzhou, 510515, People’s Republic of China,Correspondence: Xiao-Mei Tan, Tel/Fax + 86-020-61648265, Email
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Wei J, Wang X, Dong Y, Zhong X, Ren X, Song R, Ma J, Yu A, Fan Q, Yao J, Shan D, Lv F, Zheng Y, Deng Q, Li X, He Y, Fan S, Zhao C, Wang X, Yuan R, She G. Curcumae Rhizoma - combined with Sparganii Rhizoma in the treatment of liver cancer: Chemical analysis using UPLC-LTQ-Orbitrap MS n, network analysis, and experimental assessment. Front Pharmacol 2022; 13:1027687. [PMID: 36561345 PMCID: PMC9764015 DOI: 10.3389/fphar.2022.1027687] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 11/09/2022] [Indexed: 12/09/2022] Open
Abstract
Objective: Curcumae Rhizoma-Sparganii Rhizoma (CR-SR) is a traditional botanical drug pair that can promote blood circulation, remove blood stasis, and treat tumors in clinics. The aim of the present study was to investigate the therapeutic material basis and potential mechanisms of CR-SR, CR, and SR for the treatment of liver cancer. Method: The chemical profile analyses of CR-SR, CR, and SR were performed by molecular networking and UPLC-LTQ-Orbitrap MSn. The anti-liver cancer activities of CR-SR, CR, and SR were assessed by using a zebrafish xenograft model in vivo for the first time and detected by the HepG2 cell model in vitro. Combining the network analysis and molecular docking, real-time quantitative polymerase chain reaction (RT-qPCR) experiments were undertaken to further explore the mechanisms of CR-SR, CR, and SR for the treatment of liver cancer. Results: In total, 65 components were identified in CR-SR, CR, and SR. Based on the clusters of molecular networking, a total of 12 novel diarylheptanoids were identified from CR-SR and CR. By combining our results with information from the literature, 32 sesquiterpenoids and 21 cyclic dipeptides were identified from CR-SR, CR, and SR. The anti-liver cancer activities were observed in both the drug pair and the single botanical drugs in vitro and in vivo, and the order of activity was CR-SR > CR > SR. They could downregulate the expression of proto-oncogene tyrosine-protein kinase Src (SRC), epidermal growth factor receptor (EGFR), estrogen receptor-α (ESR1), prostaglandin endoperoxide synthase 2 (PTGS2), and amyloid precursor protein (APP). Conclusion: Taken together, the present study provided an experimental basis for the therapeutic material basis and potential molecular mechanisms of CR-SR, CR, and SR. This study provided a novel insight for objective clinical treatment of liver cancer.
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Affiliation(s)
- Jing Wei
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China,Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing, China
| | - Xiaoping Wang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China,Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing, China
| | - Ying Dong
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China,Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing, China
| | - Xiangjian Zhong
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China,Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing, China
| | - Xueyang Ren
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China,Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing, China
| | - Ruolan Song
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China,Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing, China
| | - Jiamu Ma
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China,Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing, China
| | - Axiang Yu
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China,Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing, China
| | - Qiqi Fan
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China,Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing, China
| | - Jianling Yao
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China,Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing, China
| | - Dongjie Shan
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China,Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing, China
| | - Fang Lv
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China,Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing, China
| | - Yuan Zheng
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China,Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing, China
| | - Qingyue Deng
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China,Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing, China
| | - Xianxian Li
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China,Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing, China
| | - Yingyu He
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China,Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing, China
| | - Shusheng Fan
- State Key Laboratory of Natural Medicines, New Drug Screening Center, Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing, China
| | - Chongjun Zhao
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China,Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing, China
| | - Xiuhuan Wang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China,Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing, China,Beijing Huilongguan Hospital, Peking University HuiLongGuan Clinical Medical School, Beijing, China,*Correspondence: Xiuhuan Wang, ; Ruijuan Yuan, ; Gaimei She,
| | - Ruijuan Yuan
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China,*Correspondence: Xiuhuan Wang, ; Ruijuan Yuan, ; Gaimei She,
| | - Gaimei She
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China,Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing, China,*Correspondence: Xiuhuan Wang, ; Ruijuan Yuan, ; Gaimei She,
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Yu CC, Liu LB, Chen SY, Wang XF, Wang L, Du YJ. Ancient Chinese Herbal Recipe Huanglian Jie Du Decoction for Ischemic Stroke: An Overview of Current Evidence. Aging Dis 2022; 13:1733-1744. [PMID: 36465168 PMCID: PMC9662271 DOI: 10.14336/ad.2022.0311] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Accepted: 03/11/2022] [Indexed: 09/30/2023] Open
Abstract
Ischemic stroke is a major cause of mortality and neurological morbidity worldwide. The underlying pathophysiology of ischemic stroke is highly complicated and correlates with various pathological processes, including neuroinflammation, oxidative stress injury, altered cell apoptosis and autophagy, excitotoxicity, and acidosis. The current treatment for ischemic stroke is limited to thrombolytic therapy such as recombinant tissue plasminogen activator. However, tissue plasminogen activator is limited by a very narrow therapeutic time window (<4.5 hours), selective efficacy, and hemorrhagic complication. Hence, the development of novel therapies to prevent ischemic damage to the brain is urgent. Chinese herbal medicine has a long history in treating stroke and its sequela. In the past decades, extensive studies have focused on the neuroprotective effects of Huanglian Jie Du decoction (HLJDD), an ancient and classical Chinese herbal formula that can treat a wide spectrum of disorders including ischemic stroke. In this review, the current evidence of HLJDD and its bioactive components for ischemic stroke is comprehensively reviewed, and their potential application directions in ischemic stroke management are discussed.
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Affiliation(s)
- Chao-Chao Yu
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China.
- Department of Integrated Chinese and Western Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China.
| | - Le-Bin Liu
- Department of Rehabilitation Medicine, Hubei Rongjun Hospital, Wuhan, Hubei, China.
| | - Shi-Yuan Chen
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China.
| | - Xiao-Fei Wang
- Department of Rehabilitation Medicine, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, Hubei, China.
| | - Li Wang
- College of Acupuncture and Orthopedics, Hubei University of Chinese Medicine, Wuhan, Hubei, China.
| | - Yan-Jun Du
- College of Acupuncture and Orthopedics, Hubei University of Chinese Medicine, Wuhan, Hubei, China.
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Zhao Y, Li H, Li X, Sun Y, Shao Y, Zhang Y, Liu Z. Network pharmacology-based analysis and experimental in vitro validation on the mechanism of Paeonia lactiflora Pall. in the treatment for type I allergy. BMC Complement Med Ther 2022; 22:199. [PMID: 35879791 PMCID: PMC9317138 DOI: 10.1186/s12906-022-03677-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 07/14/2022] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
The incidence of allergic reaction is increasing year by year, but the specific mechanism is still unclear. Paeonia lactiflora Pall.(PLP) is a traditional Chinese medicine with various pharmacological effects such as anti-tumor, anti-inflammatory, and immune regulation. Previous studies have shown that PLP has potential anti-allergic activity. However, there is still no comprehensive analysis of the targeted effects and exact molecular mechanisms of the anti-allergic components of PLP. This study aimed to reveal the mechanism of PLP. in the treatment of type I allergy by combining network pharmacological methods and experimental verification.
Methods
First, we used the traditional Chinese medicine systems pharmacology (TCMSP) database and analysis platform to screen the main components and targets of PLP, and then used databases such as GeneCards to retrieve target information related to ‘allergy’. Protein–protein interaction (PPI) analysis obtained the core target genes in the intersection target, and then imported the intersection target into the David database for gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis. Furthermore, the therapeutic effect of paeoniflorin, the main component of PLP, on IgE-induced type I allergy was evaluated in vitro.
Results
GO analysis obtained the main biological processes, cell components and molecular functions involved in the target genes. KEGG analysis screened out MAPK1, MAPK10, MAPK14 and TNF that have a strong correlation with PLP anti-type I allergy, and showed that PLP may pass through signal pathways such as IgE/FcεR I, PI3K/Akt and MAPK to regulate type I allergy. RT-qPCR and Western Blot results confirmed that paeoniflorin can inhibit the expression of key genes and down-regulate the phosphorylation level of proteins in these signal pathways. It further proved the reliability of the results of network pharmacology research.
Conclusion
The results of this study will provide a basis for revealing the multi-dimensional regulatory mechanism of PLP for the treatment of type I allergy and the development of new drugs.
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Yang PW, Xu PL, Cheng CS, Jiao JY, Wu Y, Dong S, Xie J, Zhu XY. Integrating network pharmacology and experimental models to investigate the efficacy of QYHJ on pancreatic cancer. JOURNAL OF ETHNOPHARMACOLOGY 2022; 297:115516. [PMID: 35817247 DOI: 10.1016/j.jep.2022.115516] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Revised: 06/19/2022] [Accepted: 06/26/2022] [Indexed: 06/15/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The Qingyihuaji decoction (QYHJ) is composed of seven herbs: Scutellaria barbata D.Don (Banzhilian, HSB), Gynostemma pentaphyllum (Thunb.) Makino (Jiaogulan, GP), Oldenlandia diffusa (Willd.) Roxb. (Baihuasheshecao, HDH), Ganoderma lucidum (Leyss. ex Fr.) Karst. (Lingzhi, GL), Myristica fragrans Houtt. (Doukou, AK), and Amorphophallus kiusianus (Makino) Makino (Sheliugu, RA), and Coix lacryma-jobi var. ma-yuen (Rom.Caill.) Stapf (Yiyiren, CL). QYHJ has been reported to exhibit clinical efficacy in the treatment of pancreatic adenocarcinoma (PAAD). However, the molecular mechanism remains unclear. AIM OF THE STUDY This study explores the therapeutic mechanism of QYHJ in the treatment of PAAD using network pharmacology to identify related targets and pathways in vivo and in vitro. MATERIALS AND METHODS The bioactive compounds of QYHJ were retrieved and screened using the ADME network pharmacology approach, followed by compound-target prediction and overlapping genes between PAAD oncogenes and QYHJ target genes. The compound-target-pathway network was established using The KEGG pathway, GO analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analysis to identify potential action pathways. The effects of QYHJ on PAAD were evaluated in vivo and in vitro, and the predicted targets and potential pathways related to QYHJ in PAAD treatment were evaluated using qRT-PCR and immunoblotting. RESULTS A total of 68 bioactive compounds of QYHJ fulfilled the ADME screening criterion, and their respective 242 target genes were retrieved. The compound-target-disease network identified 11 possible target genes. The KEGG pathway analysis showed significant enrichment of pathways in cancers, involving regulating cancer-related pathways of inflammation, oxidative stress, and apoptosis. Furthermore, QYHJ inhibited PAAD growth in vivo; suppressed cell proliferation, invasion, and migration of PAAD; and induced cellular apoptosis in vitro. The qRT-PCR results showed that QYHJ suppressed the mRNA expression of ICAM1, VCAM1, and Bcl2, and increased that of HMOX1 and NQO1. Immunoblotting revealed changes in the PI3K/AKT/mTOR, Keap1/Nrf2/HO-1/NQO1, and Bcl2/Bax pathways upon QYHJ treatment. CONCLUSIONS QYHJ can suppress PAAD growth and progression through various mechanisms, including anti-inflammation and apoptosis-induction.
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Affiliation(s)
- Pei-Wen Yang
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China
| | - Pan-Ling Xu
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Chinese Integrative Medicine Oncology, The First Affiliated Hospital of Anhui Medical University, 230022, Hefei, Anhui, China
| | - Chien-Shan Cheng
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China; Department of Traditional Chinese Medicine, Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital, 200025, Shanghai, China
| | - Ju-Ying Jiao
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China
| | - Yuan Wu
- Department of Traditional Chinese Medicine, Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital, 200025, Shanghai, China
| | - Shu Dong
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China
| | - Jing Xie
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China.
| | - Xiao-Yan Zhu
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China.
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Wang S, Yang XX, Li TJ, Zhao L, Bao YR, Meng XS. Analysis of the absorbed constituents and mechanism of liquidambaris fructus extract on hepatocellular carcinoma. Front Pharmacol 2022; 13:999935. [PMID: 36110518 PMCID: PMC9468745 DOI: 10.3389/fphar.2022.999935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Accepted: 08/09/2022] [Indexed: 11/13/2022] Open
Abstract
Background: Hepatocellular carcinoma (HCC) refers to one of the top 10 cancers in terms of morbidity and mortality globally, seriously influencing people’s lives. First recorded in Compendium of Materia Medica, liquidambaris fructus (LF) generates definite anti-liver tumor effect. However, its effective substances and mechanism remain to be elucidated.Methods: Serum pharmacochemistry and UPLC-QTOF-MS technologies were employed to explore the plasma of rats after intragastric administration of liquidambaris fructus extract (LFE) in order to find the active ingredients. Subsequently, DEN-induced rat liver cancer model was established with the purpose of investigating the anti-tumor activity of LFE from physiological, pathological and biochemical aspects. Finally, non-target metabonomics combined with q-PCR and Western blot methods were adopted for revealing the mechanism.Results: Totally 11 prototype blood transfused ingredients, including imperatorin and phellopterin were detected. LFE presents excellent impact on enhancing the quality of life, prolonging the life cycle, reducing inflammatory reaction, protecting hepatocytes, improving body immunity and killing liver tumor cells. Altogether 82 endogenous differential metabolites were found in metabonomics, suggesting that LFE can treat HCC by acting on key targets of PTEN/PI3K/Akt pathway and fatty acid metabolism. Further research also verified that LFE can upregulate the relative expression levels of PTEN, PDCD4, Caspase 9, Caspase 3, Bax and Bad as well as lower the relative expression levels of PI3K, AKT, VEGFA and Bcl-2.Conclusion: This study revealed the pharmacodynamic material basis of LFE in the treatment of HCC, and from the perspective of metabolomics proved that the effects of inhibiting the growth of tumor cells, promoting tumor cell apoptosis, reducing inflammatory reaction, protecting hepatocytes, improving the survival state of tumor rats, and prolonging the life cycle are related to its impact on PTEN/PI3K/Akt, fatty acid metabolism and other key signal pathways.
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Affiliation(s)
- Shuai Wang
- College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, China
- Liaoning Multi-Dimensional Analysis of Traditional Chinese Medicine Technical Innovation Center, Dalian, China
- Liaoning Province Modern Chinese Medicine Research Engineering Laboratory, Dalian, China
| | - Xin-Xin Yang
- College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, China
- Liaoning Multi-Dimensional Analysis of Traditional Chinese Medicine Technical Innovation Center, Dalian, China
- Liaoning Province Modern Chinese Medicine Research Engineering Laboratory, Dalian, China
| | - Tian-Jiao Li
- College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, China
- Liaoning Multi-Dimensional Analysis of Traditional Chinese Medicine Technical Innovation Center, Dalian, China
- Liaoning Province Modern Chinese Medicine Research Engineering Laboratory, Dalian, China
| | - Lin Zhao
- College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, China
- Liaoning Multi-Dimensional Analysis of Traditional Chinese Medicine Technical Innovation Center, Dalian, China
- Liaoning Province Modern Chinese Medicine Research Engineering Laboratory, Dalian, China
| | - Yong-Rui Bao
- College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, China
- Liaoning Multi-Dimensional Analysis of Traditional Chinese Medicine Technical Innovation Center, Dalian, China
- Liaoning Province Modern Chinese Medicine Research Engineering Laboratory, Dalian, China
- *Correspondence: Yong-Rui Bao, ; Xian-Sheng Meng,
| | - Xian-Sheng Meng
- College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, China
- Liaoning Multi-Dimensional Analysis of Traditional Chinese Medicine Technical Innovation Center, Dalian, China
- Liaoning Province Modern Chinese Medicine Research Engineering Laboratory, Dalian, China
- *Correspondence: Yong-Rui Bao, ; Xian-Sheng Meng,
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Ren Y, Gao F, Li B, Yuan A, Zheng L, Zhang Y. A precise efficacy determination strategy of traditional Chinese herbs based on Q-markers: Anticancer efficacy of Astragali radix as a case. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 102:154155. [PMID: 35580440 DOI: 10.1016/j.phymed.2022.154155] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/20/2022] [Revised: 05/02/2022] [Accepted: 05/04/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND As a "multi-components and multi-efficacy" complex system, traditional Chinese herbs are universally distributed and applied in treating clinical diseases. However, the efficacy deviation and ambiguous clinical location are affected by different effects and content of components caused by uncertain factors in the production process. It further restricts resource allocation and clinical medication and hinders modernization and globalization. In this study, a precise efficacy determination strategy was innovatively proposed, aiming to quantitatively predict the efficacy of herbs and obtain precise medicinal materials. Quality-markers (Q-markers) characterizing the efficacy are conducive to achieving precise efficacy determination. PURPOSE With the anticancer efficacy of Astragali radix (AR) as a case, the present study was designed to establish a methodology for precise efficacy determination based on Q-markers characterizing specific efficacy. METHODS Guided by the basic principles of Q-markers, the potential Q-markers characterizing the anticancer efficacy of AR were screened through molecular simulation and network pharmacology. The activity of Q-markers was evaluated on MDA-MB-231 cells, and the content of Q-markers was determined by HPLC. A quantitative efficacy prediction model of the relationship between the influencing factors and anticancer efficacy was further constructed through the effect-constituents index (ECI) and machine learning and verified by biotechnology, which can be directly applied to predict the efficacy in numerous samples. RESULTS Astragaloside I, astragaloside II, and astragaloside III inhibited the proliferation of MDA-MB-231 cells and were successfully quantified in AR samples, reflecting the effectiveness and measurability of Q-markers. Gradient Boost Regression showed the best performance in the quantitative efficacy prediction model with EVtest= 0.815, R2test= 0.802. The results of precise efficacy determination indicated that 1-2-3 (Wuzhai, Shanxi, two years, C segment) sample performed best in 54 batches of AR samples with biased anticancer efficacy. Furthermore, AR samples with higher ECI had higher anticancer efficacy and vice versa. CONCLUSION The precise efficacy determination strategy established in the present study is reliable and proved in the AR case, which is expected to support resource allocation optimization, efficacy stability improvement, and precise clinical medication achievement.
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Affiliation(s)
- Yue Ren
- Key Laboratory of TCM-information Engineer of State Administration of TCM, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Fengfeng Gao
- Key Laboratory of TCM-information Engineer of State Administration of TCM, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Beiyan Li
- Key Laboratory of TCM-information Engineer of State Administration of TCM, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Anlei Yuan
- Key Laboratory of TCM-information Engineer of State Administration of TCM, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Lulu Zheng
- Key Laboratory of TCM-information Engineer of State Administration of TCM, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Yanling Zhang
- Key Laboratory of TCM-information Engineer of State Administration of TCM, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.
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Jiang J, Yang Z, Hou G, Yao X, Jiang J. The potential mechanism of Chebulae Fructus in the treatment of hepatocellular carcinoma on the basis of network pharmacology. Ann Hepatol 2022; 27:100701. [PMID: 35351639 DOI: 10.1016/j.aohep.2022.100701] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Revised: 02/24/2022] [Accepted: 02/24/2022] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Hepatocellular carcinoma (HCC) ranks third on the list of the leading cause for cancer death globally. The treatment of HCC patients is unsatisfactory. However, the traditional Chinese medicine Chebulae Fructus has potential efficacy in the treatment of HCC. MATERIALS AND METHODS We mined the active ingredients of Chebulae Fructus and its main targets from the Traditional Chinese Medicine Systems Pharmacology database. HCC-related datasets were downloaded from The Cancer Genome Atlas database and differentially expressed genes (DEGs) in HCC were obtained by differential expression analysis. Top10 small molecule compounds capable of reversing HCC pathology were screened by the Connectivity Map database based on DEGs. Ellipticine, an extract of Chebulae Fructus, had the potential to reverse HCC pathology. Protein-Protein Interaction (PPI) networks of DEGs in HCC were constructed using STRING. Eighteen potential targets of Chebulae Fructus for the treatment of HCC were obtained by taking intersection of DEGs in HCC with targets corresponding to the active constituents of Chebulae Fructus. In addition, MTT assay was also employed to examine the effect of ellipticine on HCC cell viability. RESULTS It has been shown that ellipticine and ellagic acid have antitumor activity. Random Walk with Restart analysis of PPI networks was performed using potential targets as seeds, and the genes with the top 50 affinity coefficients were selected to construct a drug-active constituent-gene interaction network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of key genes involved in the treatment of HCC with Chebulae Fructus demonstrated that these genes were mainly enriched in signaling pathways related to tumor metabolism such as cAMP signaling pathway and Ras signaling pathway. Finally, it was verified by MTT assay that proliferation of HCC cells could be remarkably hindered. CONCLUSIONS We excavated ellipticine, a key active constituent of Chebulae Fructus, by network pharmacology, and elucidated the signaling pathways involved in Chebulae Fructus, providing a theoretical basis for the use of Chebulae Fructus for HCC clinical application.
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Affiliation(s)
- Jialu Jiang
- The First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Department of Oncology, Jiaxing, China
| | - Zhiping Yang
- The First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Department of Oncology, Jiaxing, China
| | - Guoxin Hou
- The First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Department of Oncology, Jiaxing, China
| | - Xuming Yao
- The First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Department of Oncology, Jiaxing, China
| | - Jin Jiang
- The First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Department of Oncology, Jiaxing, China.
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Exploration of the Molecular Mechanism of Danzhi Xiaoyao Powder in Endometrial Cancer through Network Pharmacology. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:8330926. [PMID: 35774749 PMCID: PMC9239783 DOI: 10.1155/2022/8330926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 05/26/2022] [Indexed: 11/17/2022]
Abstract
Endometrial cancer (EC) is a common malignant tumor of the female reproductive system. Current treatments such as surgery and long-term hormone therapy are ineffective and have side effects. Danzhi Xiaoyao powder (DXP) can inhibit the growth of EC cells and induce apoptosis, but the pharmacological and molecular mechanisms of anticancer effects are still unclear. In this study, active components and potential targets of DXP were obtained from public databases. Protein effects and regulatory pathways of common targets were analyzed by protein-protein interaction (PPI), GO and KEGG. The results of network pharmacology showed that there are 87 common targets between EC and DXP. GO enrichment analysis showed that these targets were associated with response to oxidative stress, response to nutrient levels, hormone receptor binding and nuclear hormone receptor binding, etc. The results of KEGG analysis indicated that IL-17, TNF, PI3K/AKT, and RAS/RAF/MEK/ERK (ERK) signaling pathway were enriched in the anti-EC of DXP. Additionally, we cultured HEC-1B and KLE cells for validate experiments. DXP showed an inhibition of proliferation, migration, and cell cycle of both cells. Moreover, the expression of RAS, p-RAF, p-MEK, ERK, and p-ERK related proteins were downregulated. In conclusion, DXP might inhibit the proliferation of EC cells via apoptosis. Furthermore, DXP-induced inhibition of EC development might involve RAS/RAF/MEK/ERK pathway.
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Guo W, Cao P, Wang X, Hu M, Feng Y. Medicinal Plants for the Treatment of Gastrointestinal Cancers From the Metabolomics Perspective. Front Pharmacol 2022; 13:909755. [PMID: 35833022 PMCID: PMC9271783 DOI: 10.3389/fphar.2022.909755] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 05/23/2022] [Indexed: 12/27/2022] Open
Abstract
Gastrointestinal cancer (GIC), primarily including colorectal cancer, gastric cancer, liver cancer, pancreatic cancer, and esophageal cancer, is one of the most common causes of cancer-related deaths with increasing prevalence and poor prognosis. Medicinal plants have been shown to be a great resource for the treatment of GIC. Due to their complex manifestations of multi-component and multi-target, the underlying mechanisms how they function against GIC remain to be completely deciphered. Cell metabolism is of primary importance in the initialization and development of GIC, which is reported to be a potential target. As an essential supplement to the newest “omics” sciences, metabolomics focuses on the systematic study of the small exogenous and endogenous metabolites involved in extensive biochemical metabolic pathways of living system. In good agreement with the systemic perspective of medicinal plants, metabolomics offers a new insight into the efficacy assessment and action mechanism investigation of medicinal plants as adjuvant therapeutics for GIC therapy. In this review, the metabolomics investigations on metabolism-targeting therapies for GIC in the recent 10 years were systematically reviewed from five aspects of carbohydrate, lipid, amino acid, and nucleotide metabolisms, as well as other altered metabolisms (microbial metabolism, inflammation, and oxidation), with particular attention to the potential of active compounds, extracts, and formulae from medicinal plants. Meanwhile, the current perspectives and future challenges of metabolism-targeting therapies of medicinal plants for GIC were also discussed. In conclusion, the understanding of the action mechanisms of medicinal plants in GIC from the metabolomics perspective will contribute to the clinical application of potential candidates from the resourceful medicinal plants as novel and efficient adjuvant therapeutics for GIC therapy.
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Affiliation(s)
- Wei Guo
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan, China
| | - Peng Cao
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan, China
| | - Xuanbin Wang
- Laboratory of Chinese Herbal Pharmacology, Department of Pharmacy, Renmin Hospital, Hubei University of Medicine, Shiyan, China
| | - Min Hu
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan, China
- *Correspondence: Min Hu, ; Yibin Feng,
| | - Yibin Feng
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- *Correspondence: Min Hu, ; Yibin Feng,
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Khan SA, Lee TKW. Network-Pharmacology-Based Study on Active Phytochemicals and Molecular Mechanism of Cnidium monnieri in Treating Hepatocellular Carcinoma. Int J Mol Sci 2022; 23:5400. [PMID: 35628212 PMCID: PMC9140548 DOI: 10.3390/ijms23105400] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Revised: 05/06/2022] [Accepted: 05/10/2022] [Indexed: 02/01/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a malignancy with a high mortality rate globally. For thousands of years, Cnidium monnieri has been used to treat human ailments and is regarded as a veritable treasure trove for drug discovery. This study has investigated the key active phytochemicals and molecular mechanisms of Cnidium monnieri implicated in curing HCC. We utilized the TCMSP database to collect data on the phytochemicals of Cnidium monnieri. The SwissTargetPrediction website tool was used to predict the targets of phytochemicals of Cnidium monnieri. HCC-related genes were retrieved from OncoDB.HCC and Liverome, two liver-cancer-related databases. Using the DAVID bioinformatic website tool, Gene Ontology (GO) and KEGG enrichment analysis were performed on the intersecting targets of HCC-related genes and active phytochemicals in Cnidium monnieri. A network of active phytochemicals and anti-HCC targets was constructed and analyzed using Cytoscape software. Molecular docking of key active phytochemicals was performed with anti-HCC targets using AutoDock Vina (version 1.2.0.). We identified 19 active phytochemicals in Cnidium monnieri, 532 potential targets of these phytochemicals, and 566 HCC-related genes. Results of GO enrichment indicated that Cnidium monnieri might be implicated in affecting gene targets involved in multiple biological processes, such as protein phosphorylation, negative regulation of the apoptotic process, which could be attributed to its anti-HCC effects. KEGG pathway analyses indicated that the PI3K-AKT signaling pathway, pathways in cancer, proteoglycans in cancer, the TNF signaling pathway, VEGF signaling pathway, ErbB signaling pathway, and EGFR tyrosine kinase inhibitor resistance are the main pathways implicated in the anti-HCC effects of Cnidium monnieri. Molecular docking analyses showed that key active phytochemicals of Cnidium monnieri, such as ar-curcumene, diosmetin, and (E)-2,3-bis(2-keto-7-methoxy-chromen-8-yl)acrolein, can bind to core therapeutic targets EGFR, CASP3, ESR1, MAPK3, CCND1, and ERBB2. The results of the present study offer clues for further investigation of the anti-HCC phytochemicals and mechanisms of Cnidium monnieri and provide a basis for developing modern anti-HCC drugs based on phytochemicals in Cnidium monnieri.
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Affiliation(s)
- Shakeel Ahmad Khan
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, 11 Yuk Choi Rd., Hung Hom, Kowloon 999077, Hong Kong
| | - Terence Kin Wah Lee
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, 11 Yuk Choi Rd., Hung Hom, Kowloon 999077, Hong Kong
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Intervention Mechanism of Hunag-Lian Jie-Du Decoction on Canonical Wnt/ β-Catenin Signaling Pathway in Psoriasis Mouse Model. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:3193572. [PMID: 35463060 PMCID: PMC9023143 DOI: 10.1155/2022/3193572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 02/28/2022] [Accepted: 03/31/2022] [Indexed: 11/24/2022]
Abstract
Background Psoriasis is a common chronic inflammatory skin disease with multifactor etiology, characterized by abnormal proliferation and differentiation of keratinocytes. Huang-Lian Jie-Du decoction (HLJDD) is a traditional Chinese medicine prescription with good clinical curative effect on psoriasis. However, its therapeutic mechanisms are still unclear. Methods The psoriasis model of SKH-1 nude mice was established by imiquimod-induced and HLJDD gavage was given. Hematoxylin and eosin staining were used to evaluate pathological morphologies, and immunohistochemistry was used to detect the expressions of Wnt1, β-catenin, and c-Myc in psoriasis mice. Western blot was used to examine the expressions of Frizzled-2, LRP5/6, GSK-3β, APC, Axin2, TCF4, LEF1, cyclin D1, TBX3, EPHB2, and NOTUM enzyme. Results In this study, HLJDD reduced skin erythema and lesions, decreased the thickness of epidermal and downregulated the expressions of Wnt1, β-catenin, and c-Myc. Western blot results showed that HLJDD reduced the expressions of Wnt receptors Frizzled-2 and LRP5/6, and Wnt downstream target genes TCF4, LEF1, cyclin D1, TBX3, and EPHB2, while upregulated destruction complex proteins GSK-3β, APC, and Axin2. Conclusions HLJDD can effectively treat psoriasis and inhibit the Wnt/β-catenin signaling pathway at multiple stages.
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Utilizing Bioinformatics Technology to Explore the Potential Mechanism of Danggui Buxue Decoction against NSCLC. DISEASE MARKERS 2022; 2022:5296830. [PMID: 35256890 PMCID: PMC8898125 DOI: 10.1155/2022/5296830] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Accepted: 02/10/2022] [Indexed: 12/12/2022]
Abstract
While lung cancer poses a serious threat to human health, non-small-cell lung cancer (NSCLC) is the most common type of lung cancer. Danggui Buxue Decoction (DBD) is a classical traditional antitumor medicine commonly used in China. However, the potential mechanism of DBD against NSCLC has not yet been expounded. Therefore, this study clarified the potential molecular mechanism and key targets of DBD in NSCLC treatment through several technological advances, such as network pharmacology, molecular docking, and bioinformatics. Firstly, the relative active ingredients and key DBD targets were analyzed, and subsequently, a drug-ingredient-target-disease network diagram was constructed for NSCLC treatment with DBD, resulting in the identification of five main active ingredients and ten core targets according to the enrichment degree. The enrichment analysis revealed that DBD can achieve the purpose of treating NSCLC through the AGE-RAGE signaling pathway in diabetic complications. Secondly, the molecular docking approach predicted that quercetin and hederagenin have the best working mechanisms with PDE3A and PTGS1, while the survival analysis results depicted that high PDE3A gene expression has a relatively poor prognosis for NSCLC patients (p < 0.05). Additionally, PDE3A is mainly distributed in the LU65 cell line that originated from Asian population. In summary, our study results showed that DBD can treat NSCLC through the synergistic correlation between multiple ingredients, multiple targets, and multiple pathways, thus effectively improving NSCLC prognosis. This study not only reflected the medicinal value of DBD but also provided a solid structural basis for future new drug developments and targeted therapies.
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Zhang W, Liu C, Li J, Lu Y, Li H, Zhuang J, Ren X, Wang M, Sun C. Tanshinone IIA: New Perspective on the Anti-Tumor Mechanism of A Traditional Natural Medicine. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2022; 50:209-239. [PMID: 34983327 DOI: 10.1142/s0192415x22500070] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
The search for natural and efficacious antineoplastic drugs, with minimal toxicity and side effects, is an important part of antitumor drug research and development. Tanshinone IIA is the most evaluated lipophilic active component of Salvia miltiorrhiza. Tanshinone IIA is a path-breaking traditional drug applied in cardiovascular treatment. It has also been found that tanshinone IIA plays an important role in the digestive, respiratory and circulatory systems, as well as in other tumor diseases. Tanshinone IIA significantly inhibits the proliferation of several types of tumors, blocks the cell cycle, induces apoptosis and autophagic death, in addition to inhibiting cell migration and invasion. Among these, the regulation of tumor-cell apoptosis signaling pathways is the key breakthrough point in several modes of antitumor therapy. The PI3K/AKT/MTOR signaling pathway and the JNK pathway are the key pathways for tanshinone IIA to induce tumor cell apoptosis. In addition to glycolysis, reactive oxygen species and signal transduction all play an active role with the participation of tanshinone IIA. Endogenous apoptosis is considered the main mechanism of tumor apoptosis induced by tanshinone IIA. Multiple pathways and targets play a role in the process of endogenous apoptosis. Tanshinone IIA can protect chemotherapy drugs, which is mainly reflected in the protection of the side effects of chemotherapy drugs, such as neurotoxicity and inhibition of the hematopoietic system. Tanshinone IIA also has a certain regulatory effect on tumor angiogenesis, which is mainly manifested in the control of hypoxia. Our findings indicated that tanshinone IIA is an effective treatment agent in the cardiovascular field and plays a significant role in antitumor therapeutics. This paper reviews the pharmacological potential and inhibitory effect of tanshinone IIA on cancer. It is greatly anticipated that tanshinone IIA will be employed as an adjuvant in the treatment of various cancers.
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Affiliation(s)
- Wenfeng Zhang
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250014, P. R. China.,School of Traditional Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, P. R. China
| | - Cun Liu
- College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250014, P. R. China
| | - Jie Li
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250014, P. R. China
| | - Yiping Lu
- Integrated Traditional Chinese and Western Medicine Center, Department of Medicine, Qingdao University, Qingdao Shandong 266000, P. R. China
| | - Huayao Li
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250014, P. R. China
| | - Jing Zhuang
- Department of Oncology, Weifang Traditional Chinese Medicine Hospital, Weifang, Shandong 261041, P. R. China
| | - Xin Ren
- Clinical Medical Colleges, Weifang Medical University, Weifang, Shandong 261000, P. R. China
| | - Mengmeng Wang
- Clinical Medical Colleges, Weifang Medical University, Weifang, Shandong 261000, P. R. China
| | - Changgang Sun
- Department of Oncology, Weifang Traditional Chinese Medicine Hospital, Weifang, Shandong 261041, P. R. China.,Qingdao Academy of Chinese Medical Sciences, Shandong University of Traditional Chinese Medicine, Qingdao, P. R. China
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Gao K, Zhu Y, Wang H, Gong X, Yue Z, Lv A, Zhou X. Network pharmacology reveals the potential mechanism of Baiying Qinghou decoction in treating laryngeal squamous cell carcinoma. Aging (Albany NY) 2021; 13:26003-26021. [PMID: 34986125 PMCID: PMC8751612 DOI: 10.18632/aging.203786] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Accepted: 11/22/2021] [Indexed: 01/20/2023]
Abstract
Context: Baiying Qinghou as a traditional Chinese medicine decoction shows anticancer property on laryngeal squamous cell carcinoma. However, little is known about the precise mechanism of Baiying Qinghou detection against laryngeal squamous cell carcinoma. Objective: This study was aimed to explore potential mechanism of therapeutic actions of Baiying Qinghou decoction on laryngeal squamous cell carcinoma. Materials and Methods: The active chemical components of Baiying Qinghou decoction were predicted, followed by integrated analysis of network pharmacology and molecular docking approach. The network pharmacology approach included target protein prediction, protein-protein interaction network construction and functional enrichment analysis. Results: Sitosterol and quercetin were predicted to be the overlapped active ingredients among three Chinese herbs of Baiying Qinghou decoction. The target proteins were closely associated with response to chemical, response to drug related biological process and cancer related pathways such as PI3K-Akt signaling, HIF-1 signaling and Estrogen signaling pathway. The target proteins of TP53, EGFR, PTGS2, NOS3 and IL1B as the key nodes in PPI network were cross-validated, among which EGFR, IL1B, NOS3 and TP53 were significantly correlated with the prognosis of patients with laryngeal squamous cell carcinoma. Finally, the binding modes of EGFR, IL1B, NOS3 and TP53 with quercetin were visualized. Discussion and Conclusion: Quercetin of Baiying Qinghou decoction showed therapeutic effect against laryngeal squamous cell carcinoma by regulating TP53, EGFR, NOS3 and IL1B involved with drug resistance and PI3K-AKT signaling pathway. TP53, EGFR, NOS3 and IL1B may be the candidate targets for the treatment of laryngeal squamous cell carcinoma.
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Affiliation(s)
- Kun Gao
- Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China.,Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China
| | - Yanan Zhu
- Department of Internal Medicine, Shandong Provincial Chest Hospital Affiliated to Shandong University, Jinan 250013, Shandong, China
| | - Hui Wang
- Department of Ultrasound, The Fifth People's Hospital of Jinan, Jinan 250022, Shandong, China
| | - Xianwei Gong
- Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China
| | - Zhiyong Yue
- Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China.,Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China
| | - Aiai Lv
- Department of Internal Medicine, Shandong Provincial Chest Hospital Affiliated to Shandong University, Jinan 250013, Shandong, China
| | - Xuanchen Zhou
- Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China.,Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China
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Dou L, Gong X, Wu Q, Mou F. Therapeutic effects of Sheng Xue Fang in a cyclophosphamide-induced anaemia mouse model. PHARMACEUTICAL BIOLOGY 2021; 59:789-798. [PMID: 34176428 PMCID: PMC8238071 DOI: 10.1080/13880209.2021.1941133] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 05/25/2021] [Accepted: 06/05/2021] [Indexed: 06/13/2023]
Abstract
CONTEXT Sheng Xue Fang (SXF) has been used to treat anaemia for decades with good efficacy. OBJECTIVE To study the effect and possible mechanism of SXF to restore haematopoietic function. MATERIALS AND METHODS Balb/c mice (10 per/group, half male, half female) were treated with SXF (three dose groups, 8.5, 17, and 22.1 g/kg) by gavage for 14 days, and cyclophosphamide (80 mg/kg) was injected on days 10-12. Only injection of cyclophosphamide (negative control) or physiological saline (blank control) were included as controls. The spleen and femur were processed for histopathology. Active components and the target of SXF were screened. The target was used for gene enrichment and protein-protein interaction (PPI) analysis. RESULTS Red blood cell relative changes in the SXF group (low: -5.50 ± 1.58%; medium: -11.11 ± 4.15%; high: -8.81 ± 2.67%) and relative negative control (26.21 ± 2.51%) significantly increased (all p < 0.01) in female mice. Haemoglobin and red blood cell-specific volume showed the same trend. However, SXF did not have significant effects on male mice. Splenic index in the medium group (4.44 ± 0.46%) relative negative control (3.38 ± 0.10%) significantly improved (p < 0.01) in female mice. Using network pharmacology, 77 active components and 337 targets were screened from SXF. These targets are closely related to the mitogen-activated protein kinase pathway. CONCLUSIONS SXF has good clinical application potential. However, the mechanism requires in-depth research. Our findings are of great significance in anaemia treatment and provide a new perspective for Chinese medicine research.
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Affiliation(s)
- Lu Dou
- Central Laboratory, Chongqing University Three Gorges Hospital, Chongqing, People's Republic of China
| | - Xue Gong
- Internal Medicine of Traditional Chinese Medicine, Chongqing University Three Gorges Hospital, Chongqing, People's Republic of China
| | - Qing Wu
- Internal Medicine of Traditional Chinese Medicine, Chongqing University Three Gorges Hospital, Chongqing, People's Republic of China
| | - Fangzheng Mou
- Internal Medicine of Traditional Chinese Medicine, Chongqing University Three Gorges Hospital, Chongqing, People's Republic of China
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Rodriguez S, Skeet K, Mehmetoglu-Gurbuz T, Goldfarb M, Karri S, Rocha J, Shahinian M, Yazadi A, Poudel S, Subramani R. Phytochemicals as an Alternative or Integrative Option, in Conjunction with Conventional Treatments for Hepatocellular Carcinoma. Cancers (Basel) 2021; 13:cancers13225753. [PMID: 34830907 PMCID: PMC8616323 DOI: 10.3390/cancers13225753] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Revised: 11/10/2021] [Accepted: 11/15/2021] [Indexed: 12/12/2022] Open
Abstract
Simple Summary Hepatocellular carcinoma (HCC) is globally ranked as the sixth most diagnosed cancer, and the second most deadly cancer. To worsen matters, there are only limited therapeutic options currently available; therefore, it is necessary to find a reservoir from which new HCC treatments may be acquired. The field of phytomedicine may be the solution to this problem, as it offers an abundance of plant-derived molecules, which show capabilities of being effective against HCC proliferation, invasion, migration, and metastasis. In our review, we collect and analyze current evidence regarding these promising phytochemical effects on HCC, and delve into their potential as future chemotherapies. Additionally, information on the signaling behind these numerous phytochemicals is provided, in an attempt to understand their mechanisms. This review makes accessible the current body of knowledge pertaining to phytochemicals as HCC treatments, in order to serve as a reference and inspiration for further research into this subject. Abstract Hepatocellular carcinoma (HCC) is the most abundant form of liver cancer. It accounts for 75–85% of liver cancer cases and, though it ranks globally as the sixth most common cancer, it ranks second in cancer-related mortality. Deaths from HCC are usually due to metastatic spread of the cancer. Unfortunately, there are many challenges and limitations with the latest HCC therapies and medications, making it difficult for patients to receive life-prolonging care. As there is clearly a high demand for alternative therapy options for HCC, it is prudent to turn to plants for the solution, as their phytochemicals have long been used and revered for their many medicinal purposes. This review explores the promising phytochemical compounds identified from pre-clinical and clinical trials being used either independently or in conjunction with already existing cancer therapy treatments. The phytochemicals discussed in this review were classified into several categories: lipids, polyphenols, alkaloids, polysaccharides, whole extracts, and phytochemical combinations. Almost 80% of the compounds failed to progress into clinical studies due to lack of information regarding the toxicity to normal cells and bioavailability. Although large obstacles remain, phytochemicals can be used either as an alternative or integrative therapy in conjunction with existing HCC chemotherapies. In conclusion, phytochemicals have great potential as treatment options for hepatocellular carcinoma.
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Affiliation(s)
- Sheryl Rodriguez
- Center of Emphasis in Cancer Research, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA; (S.R.); (T.M.-G.); (S.P.)
| | - Kristy Skeet
- Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA; (K.S.); (J.R.); (M.S.); (A.Y.)
| | - Tugba Mehmetoglu-Gurbuz
- Center of Emphasis in Cancer Research, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA; (S.R.); (T.M.-G.); (S.P.)
| | - Madeline Goldfarb
- Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA; (M.G.); (S.K.)
| | - Shri Karri
- Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA; (M.G.); (S.K.)
| | - Jackelyn Rocha
- Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA; (K.S.); (J.R.); (M.S.); (A.Y.)
| | - Mark Shahinian
- Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA; (K.S.); (J.R.); (M.S.); (A.Y.)
| | - Abdallah Yazadi
- Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA; (K.S.); (J.R.); (M.S.); (A.Y.)
| | - Seeta Poudel
- Center of Emphasis in Cancer Research, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA; (S.R.); (T.M.-G.); (S.P.)
| | - Ramadevi Subramani
- Center of Emphasis in Cancer Research, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA; (S.R.); (T.M.-G.); (S.P.)
- Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA; (K.S.); (J.R.); (M.S.); (A.Y.)
- Correspondence: ; Tel.: +1-915-215-6851
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Wang K, Lei L, Cao J, Qiao Y, Liang R, Duan J, Feng Z, Ding Y, Ma Y, Yang Z, Zhang E. Network pharmacology-based prediction of the active compounds and mechanism of Buyang Huanwu Decoction for ischemic stroke. Exp Ther Med 2021; 22:1050. [PMID: 34434264 PMCID: PMC8353622 DOI: 10.3892/etm.2021.10484] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Accepted: 02/09/2021] [Indexed: 02/06/2023] Open
Abstract
Buyang Huanwu Decoction (BYHWD) is used to promote blood circulation and is widely used in Chinese clinical practice for the treatment and prevention of ischemic cerebral vascular diseases. However, the mechanism and active compounds of BYHWD used to treat ischemic stroke are not well understood. The current study aimed to identify the potential active components of BYHWD and explore its mechanism using network pharmacology and bioinformatics analyses. The compounds of BYHWD were obtained from public databases. Oral bioavailability and drug-likeness were screened using the absorption, distribution, metabolism and excretion (ADME) criteria. Components of BYHWD, alongside the candidate targets of each component and the known therapeutic targets of ischemic stroke were collected. A network of target gene compounds and cerebral ischemia compounds was established using network pharmacology data sources. The enrichment of key targets and pathways was analyzed using STRING and DAVID databases. Moreover, three of key targets [IL6, VEGFA and hypoxia-inducible-factor-1α (HIF-1α)] were verified using western blot analysis. Network analysis determined 102 compounds in seven herbal medicines that were subjected to ADME screening. A total of 42 compounds as well as 79 genes formed the principal pathways associated with ischemic stroke. The 16 key compounds identified were baicalein, beta-carotene, baicalin, kaempferol, luteolin, quercetin, hydroxysafflor yellow A, isorhamnetin, bifendate, formononetin, calycosin, astragaloside IV, stigmasterol, sitosterol, Z-ligustilide, and dihydrocapsaicin. The core genes in this network were IL6, TNF, VEGFA, HIF-1α, MAPK1, MAPK3, JUN, STAT3, IL1B and IL10. Furthermore, the TNF, IL17, apoptosis, PI3K-Akt, toll-like receptor, MAPK, NF-κB and HIF-1 signaling pathways were identified to be associated with ischemic stroke. Compared with the control group (no treatment), BYHWD significantly inhibited the expression of IL6 and increase the expression of HIF-1α and VEGFA. Network pharmacology analyses can help to reveal close interactions between multi-components and multi-targets and enhance understanding of the potential effects of BYHWD on ischemic stroke.
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Affiliation(s)
- Kai Wang
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712046, P.R. China
| | - Lu Lei
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
| | - Jinyi Cao
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
| | - Yi Qiao
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
- Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, P.R. China
| | - Ruimin Liang
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712046, P.R. China
| | - Jialin Duan
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
| | - Zhijun Feng
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
| | - Yi Ding
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
| | - Yang Ma
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
| | - Zhifu Yang
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
| | - Enhu Zhang
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712046, P.R. China
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Wu J, Zhang F, Ruan H, Chang X, Wang J, Li Z, Jin W, Shi Y. Integrating Network Pharmacology and RT-qPCR Analysis to Investigate the Mechanisms Underlying ZeXie Decoction-Mediated Treatment of Non-alcoholic Fatty Liver Disease. Front Pharmacol 2021; 12:722016. [PMID: 34566646 PMCID: PMC8458890 DOI: 10.3389/fphar.2021.722016] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 08/26/2021] [Indexed: 01/14/2023] Open
Abstract
ZeXie Decoction (ZXD) is a traditional Chinese medicine composed of Alisma orientalis (Sam.) Juzep. and Atractylodes macrocephala Koidz. ZXD has been widely used to treat non-alcoholic fatty liver disease (NAFLD). The mechanistic basis for the pharmacological activity of ZXD, however, remains poorly understood. In this study, we used a network pharmacology approach and investigated the association between ZXD and NAFLD. We identified the active ingredients of ZXD and screened the potential targets of these ingredients, after which a database of relevant NAFLD-related targets were constructed and several enrichment analyses were performed. Furthermore, the ethanol and aqueous extracts of ZXD were prepared and experimental pharmacology validation was conducted using RT-qPCR of the non-alcoholic fatty liver disease (NAFLD) model in Sprague-Dawley (SD) rats. As a result, a herb-compound-target-pathway network model was developed, and HMGCR, SREBP-2, MAPK1, and NF-κBp65 targets were validated. The gene expression results of these four targets were consistent with those of the network pharmacology prediction. Using an integration strategy, we revealed that ZXD could treat NAFLD by targeting HMGCR, SREBP-2, MAPK1, and NF-κBp65.
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Affiliation(s)
- Jiashuo Wu
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Fangqing Zhang
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Haonan Ruan
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaoyan Chang
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jingxun Wang
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhuangzhuang Li
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Weiyi Jin
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,College of Public Health, Hebei Medical University, Shijiazhuang, China
| | - Yue Shi
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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45
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Interpreting the Molecular Mechanisms of Yinchenhao Decoction on Hepatocellular Carcinoma through Absorbed Components Based on Network Pharmacology. BIOMED RESEARCH INTERNATIONAL 2021; 2021:6616908. [PMID: 34104649 PMCID: PMC8159653 DOI: 10.1155/2021/6616908] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 04/23/2021] [Accepted: 05/07/2021] [Indexed: 12/13/2022]
Abstract
To investigate the mechanisms through which Yinchenhao decoction (YCHD) inhibits hepatocellular carcinoma (HCC), we analyzed YCHD ingredients absorbed into the bloodstream by using network pharmacology. We conducted a weighted gene coexpression network analysis on gene expression data collected from the Gene Expression Omnibus and The Cancer Genome Atlas databases to derive an HCC gene set; moreover, we used four online prediction system databases to predict the potential targets of YCHD ingredients absorbed into the bloodstream. We discovered that YCHD directly interfered with 17 HCC-related disease targets. Subsequent gene ontology enrichment analyses of these 17 disease targets revealed that YCHD exhibited effects through 17 biological processes, 7 molecular functions, and 9 cellular components. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated 14 pathways through which YCHD inhibits HCC. We observed similar trends in how the 17 small molecules interfered with the key target set. We surmised that YCHD inhibits HCC by regulating inflammatory and metabolic pathways. Network pharmacological analysis of YCHD ingredients absorbed into the bloodstream may provide new insights and serve as a new method for discovering the molecular mechanisms through which YCHD inhibits HCC.
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46
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Xia H, Liu J, Yang W, Liu M, Luo Y, Yang Z, Xie J, Zeng H, Xu R, Ling H, Zeng Q, Xu H, Fang L, Wang H, Tong P, Jin H, Yang F. Integrated Strategy of Network Pharmacological Prediction and Experimental Validation Elucidate Possible Mechanism of Bu-Yang Herbs in Treating Postmenopausal Osteoporosis via ESR1. Front Pharmacol 2021; 12:654714. [PMID: 34045964 PMCID: PMC8144472 DOI: 10.3389/fphar.2021.654714] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Accepted: 04/12/2021] [Indexed: 12/18/2022] Open
Abstract
Postmenopausal osteoporosis (PMOP) is a type of bone metabolism disease-related to estrogen deficiency with an increasing incidence. Traditional Chinese (TCM) has always been used and showed effectiveness in treating PMOP. In the current study, Bu-Yang herbs were considered to be the most frequently used and efficient TCM herbs in PMOP treatment. However, chemical and pharmacological profiles were not elucidated. Network pharmacology was conducted on representative Bu-Yang herbs (Yin-Yang-Huo. Du-Zhong, Bu-Gu-Zhi, Tu-Si-Zi) to investigate the mechanism of Bu-Yang herbs on PMOP. Chemical compounds, potential targets, and disease related genes were available from the corresponding database. Results showed that Bu-Yang herbs could interact with ESR1 and estrogen signaling pathways. For further validation, the Bu-Yang decoction (BYD), formula consisted of the above-mentioned 4 Bu-Yang herbs was presented for experimental validation. In vivo, BYD significantly reversed ovariectomy (OVX)-induced osteoporosis progress in a dose-dependent manner by up-regulation of bone mineral density and amelioration of bone microarchitecture. In vitro, BYD dramatically improved the proliferation and mineral nodules formation of osteoblasts. Both in vitro and in vivo results illustrated that the phenotype change induced by BYD is correlated with up-regulated of ESR1 and activation of the β-catenin pathway. Meanwhile, inhibition of ESR1 by ICI182, 780 blocked the osteogenic phenotype and β-catenin pathway activation induced by BYD. In conclusion, the current study suggested that Bu-Yang herbs are the most useful TCM herbs in treating PMOP. Furthermore, the integrated strategy of network pharmacology prediction with experimental validation suggested that BYD exerted its anti-PMOP via ESR1 and the downstream mechanism might be activation of the β-catenin signaling pathway.
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Affiliation(s)
- Hanting Xia
- The First Clinical College, Zhejiang Chinese Medical University, Hangzhou, China.,Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.,Department of Orthopedics, Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, China
| | - Jiangyuan Liu
- Graduated School, Jiangxi University of Chinese Medicine, Nanchang, China
| | - Wenlong Yang
- Department of Orthopedics, Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, China
| | - Min Liu
- Department of Orthopedics, Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, China
| | - Yunfeng Luo
- Graduated School, Jiangxi University of Chinese Medicine, Nanchang, China
| | - Zhijun Yang
- Graduated School, Jiangxi University of Chinese Medicine, Nanchang, China
| | - Jingbo Xie
- Department of Orthopedics, People's Hospital of Fengcheng City, Fengcheng, China
| | - Huiliang Zeng
- Department of Orthopedics, Foshan Hospital of Traditional Chinese Medicine, Foshan, China
| | - Rui Xu
- The First Clinical College, Zhejiang Chinese Medical University, Hangzhou, China.,Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Houfu Ling
- The First Clinical College, Zhejiang Chinese Medical University, Hangzhou, China.,Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Qinghe Zeng
- The First Clinical College, Zhejiang Chinese Medical University, Hangzhou, China.,Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Huihui Xu
- The First Clinical College, Zhejiang Chinese Medical University, Hangzhou, China.,Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Liang Fang
- The First Clinical College, Zhejiang Chinese Medical University, Hangzhou, China.,Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Hongyu Wang
- Graduated School, Jiangxi University of Chinese Medicine, Nanchang, China
| | - Peijian Tong
- The First Clinical College, Zhejiang Chinese Medical University, Hangzhou, China.,Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.,Department of Orthopaedic Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Hongting Jin
- The First Clinical College, Zhejiang Chinese Medical University, Hangzhou, China.,Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.,Department of Orthopaedic Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Fengyun Yang
- Graduated School, Jiangxi University of Chinese Medicine, Nanchang, China
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Feng Y, Hao F. Hansenia weberbaueriana (Fedde ex H.Wolff) Pimenov & Kljuykov Extract Suppresses Proliferation of HepG2 Cells via the PTEN-PI3K-AKT Pathway Uncovered by Integrating Network Pharmacology and Iin Vitro Experiments. Front Pharmacol 2021; 12:620897. [PMID: 33967754 PMCID: PMC8097175 DOI: 10.3389/fphar.2021.620897] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Accepted: 03/25/2021] [Indexed: 12/13/2022] Open
Abstract
Previous studies have shown that Hansenia weberbaueriana (Fedde ex H.Wolff) Pimenov & Kljuykov extracts (HWEs) have antitumor activity, but their mechanism in vitro is still unclear. In this study, we first combined network pharmacology with experimental evaluation and applied a comprehensive strategy to explore and prove the therapeutic potential and potential mechanism of HWE. The mRNA expression profiles of PTEN, PIK3A, and AKT1 are from the Cancer Cell Line Encyclopedia (CCLE) of the Broad Institute. Our results showed that HWE has a good inhibition on HepG2 cells, and a slight inhibition on other cells. The results of the CCLE database showed that PTEN/PIK3A/AKT1 mRNA expression was up-regulated in HepG2 cells. Through further study, it was found that HWE increased the release of LDH, induced early and late apoptosis, and increased ROS levels in HepG2 cells. Western blot showed that HWE regulates the expression of mitochondrial apoptosis-related proteins. Meanwhile, the expression of PTEN was increased, and the expression of phosphorylated PI3K and Akt was down-regulated after HWE treatment. Our results show that HWE promotes HepG2 cell apoptosis via the PTEN-PI3K-Akt signaling pathway. This study is the first to report the potential role of HWE in the treatment of liver cancer.
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Affiliation(s)
- Yueqin Feng
- Department of Ultrasound, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Fengjin Hao
- Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, China
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48
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Li M, Shang H, Wang T, Yang SQ, Li L. Huanglian decoction suppresses the growth of hepatocellular carcinoma cells by reducing CCNB1 expression. World J Gastroenterol 2021; 27:939-958. [PMID: 33776365 PMCID: PMC7968131 DOI: 10.3748/wjg.v27.i10.939] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Revised: 01/03/2021] [Accepted: 02/01/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the most prevalent cancers in human populations worldwide. Huanglian decoction is one of the most important Chinese medicine formulas, with the potential to treat cancer. AIM To investigate the role and mechanism of Huanglian decoction on HCC cells. METHODS To identify differentially expressed genes (DEGs), we downloaded gene expression profile data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma and Gene Expression Omnibus (GSE45436) databases. We obtained phytochemicals of the four herbs of Huanglian decoction from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. We also established a regulatory network of DEGs and drug target genes and subsequently analyzed key genes using bioinformatics approaches. Furthermore, we conducted in vitro experiments to explore the effect of Huanglian decoction and to verify the predictions. In particular, the CCNB1 gene was knocked down to verify the primary target of this decoction. Through the identification of the expression levels of key proteins, we determined the primary mechanism of Huanglian decoction in HCC. RESULTS Based on the results of the network pharmacological analysis, we revealed 5 bioactive compounds in Huanglian decoction that act on HCC. In addition, a protein-protein interaction network analysis of the target genes of these five compounds as well as expression and prognosis analyses were performed in tumors. CCNB1 was confirmed to be the primary gene that may be highly expressed in tumors and was significantly associated with a worse prognosis. We also noted that CCNB1 may serve as an independent prognostic indicator in HCC. Moreover, in vitro experiments demonstrated that Huanglian decoction significantly inhibited the growth, migration, and invasiveness of HCC cells and induced cell apoptosis and G2/M phase arrest. Further analysis showed that the decoction may inhibit the growth of HCC cells by downregulating the CCNB1 expression level. After Huanglian decoction treatment, the expression levels of Bax, caspase 3, caspase 9, p21 and p53 in HCC cells were increased, while the expression of CDK1 and CCNB1 was significantly decreased. The p53 signaling pathway was also found to play an important role in this process. CONCLUSION Huanglian decoction has a significant inhibitory effect on HCC cells. CCNB1 is a potential therapeutic target in HCC. Further analysis showed that Huanglian decoction can inhibit HCC cell growth by downregulating the expression of CCNB1 to activate the p53 signaling pathway.
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Affiliation(s)
- Min Li
- Department of Gastroenterology, Zibo Central Hospital, Zibo 255036, Shandong Province, China
| | - Hua Shang
- Department of Gastroenterology, Zibo Central Hospital, Zibo 255036, Shandong Province, China
| | - Tao Wang
- Department of General Surgery, Zibo Central Hospital, Zibo 255036, Shandong Province, China
| | - Shui-Qing Yang
- School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China
| | - Lei Li
- School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China
- Department of Pathology, University of Otago, Dunedin px806, New Zealand
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Liu SH, Chen PS, Huang CC, Hung YT, Lee MY, Lin WH, Lin YC, Lee AYL. Unlocking the Mystery of the Therapeutic Effects of Chinese Medicine on Cancer. Front Pharmacol 2021; 11:601785. [PMID: 33519464 PMCID: PMC7843369 DOI: 10.3389/fphar.2020.601785] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Accepted: 11/05/2020] [Indexed: 12/22/2022] Open
Abstract
Over the past decade, the rise of cancer immunotherapy has coincided with a remarkable breakthrough in cancer therapy, which attracted increased interests in public. The scientific community clearly showed that the emergence of immunotherapy is an inevitable outcome of a holistic approach for cancer treatment. It is well established that traditional Chinese medicine (TCM) utilizes the principle of homeostasis and balance to adjust the healthy status of body. TCM treatment toward cancer has a long history, and the diagnosis and treatment of tumors were discussed in the ancient and classical literatures of Chinese medicine, such as the Yellow Emperor’s Inner Canon. Precious heritage has laid the foundation for the innovation and development of cancer treatment with TCM. The modern study indicated that TCM facilitates the treatment of cancer and enhances the survival rate and life expectancy of patients. However, the pharmacological mechanisms underlying these effects are not yet completely understood. In addition, physicians cannot always explain why the TCM treatment is effective and the mechanism of action cannot be explained in scientific terms. Here, we attempted to provide insights into the development of TCM in the treatment and interpret how TCM practitioners treat cancer through six general principles of TCM by using modern scientific language and terms based on newly discovered evidence.
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Affiliation(s)
- Shao-Hsiang Liu
- Celgen Biotech, Taipei, Taiwan.,Taiwan Instrument Research Institute, National Applied Research Laboratories, Zhubei, Taiwan
| | | | - Chun-Chieh Huang
- Department of Chinese Medicine, Taitung Christian Hospital, Taitung, Taiwan
| | - Yi-Tu Hung
- HanPoo Chinese Medical Clinic, Taipei, Taiwan
| | - Mei-Ying Lee
- Chinese Medicine Women Doctors Association, Taipei, Taiwan
| | | | | | - Alan Yueh-Luen Lee
- National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan.,Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
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50
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An N, Li Y, Huang X, Chen C, Xie Y. Huanglian Jiedu Decoction for treatment of multiple myeloma: A protocol for a systematic review and meta-analysis. Medicine (Baltimore) 2020; 99:e22378. [PMID: 33371054 PMCID: PMC7748179 DOI: 10.1097/md.0000000000022378] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2020] [Accepted: 08/26/2020] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Multiple myeloma can lead to lots of clinical problems including pain, fatigue, anemia, infections, renal failure, and so on. Huanglian Jiedu Decoction is a common conservative treatment for this disease in China. Therefore, we conducted a systematic review and meta-analysis to explore the efficacy of Huanglian Jiedu Decoction in the treatment of multiple myeloma. METHODS A systematic literature search for studies will be performed in 8 databases, including PubMed, Web of Science, Embase, the Cochrane library, ClinicalTrials.gov databases, Chinese National Knowledge Infrastructure Database, Wanfang database, and VIP database. The methodological quality of the included studies using the risk bias assessment tool of Cochrane. And the level of evidence for results is assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. Statistical analysis is conducted with Revman 5.3. RESULTS This systematic review and meta-analysis will provide a synthesis of existed evidences for Huanglian Jiedu Decoction on multiple myeloma. CONCLUSION The conclusion of this study will provide evidence to assess effectiveness of Huanglian Jiedu Decoction on multiple myeloma, which can further guide clinical decision-making. INPLASY REGISTRATION NUMBER INPLASY202060094.
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