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Zhan XZ, Wei TH, Huang C, Yu H, Chen XL, Kong XT, Shang ZH, Sun SL, Lu MY, Ni HW. Modulating JAK2/STAT3 signaling by quercetin in Qiling Baitouweng Tang: a potential therapeutic approach for diffuse large B-cell lymphoma. Mol Divers 2025; 29:2407-2431. [PMID: 39369170 DOI: 10.1007/s11030-024-10999-2] [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: 06/26/2024] [Accepted: 09/24/2024] [Indexed: 10/07/2024]
Abstract
Qiling Baitouweng Tang (QLBTWT) is a traditional clinical formula for treating diffuse large B-cell lymphoma (DLBCL), but its molecular action is not fully understood. This research is utilized in silico analysis and liquid chromatography tandem mass spectrometry (LC‒MS/MS) to identify the active constituents of QLBTWT with anti-DLBCL properties and their targets. The study identified 14 compounds, including quercetin, naringenin, and astilbin, as potentially effective against DLBCL. Molecular modeling highlighted the favorable interaction of quercetin with the JAK2 protein. In vitro studies confirmed the ability of quercetin to inhibit DLBCL cell growth and migration while inducing apoptosis and causing G2/M phase cell cycle arrest. Molecular dynamics simulations revealed that quercetin binds to JAK2 as a type II inhibitor. In vivo studies in U2932 xenograft models demonstrated that QLBTWT inhibited tumor growth in a dose-dependent manner, which was associated with the JAK2/STAT3 signaling pathway. Overall, this study elucidates the therapeutic effect of QLBTWT on DLBCL through quercetin-mediated suppression of the JAK2/STAT3 pathway, offering novel therapeutic insights for DLBCL.
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Affiliation(s)
- Xin-Zhuo Zhan
- Department of Hematology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Tian-Hua Wei
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Chen Huang
- Department of Hematology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China
| | - Hui Yu
- Department of Hematology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China
| | - Xiao-Li Chen
- Department of Hematology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China
| | - Xiang-Tu Kong
- Department of Hematology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China
| | - Zhi-Hao Shang
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Shan-Liang Sun
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 211198, China.
| | - Meng-Yi Lu
- Department of Biostatistics, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, China.
| | - Hai-Wen Ni
- Department of Hematology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China.
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Zu GX, Tang JQ, Huang HL, Han T. Validation and analysis of key factors of Banxia Xiexin decoction against gastric cancer. World J Gastrointest Oncol 2025; 17:104737. [DOI: 10.4251/wjgo.v17.i5.104737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2024] [Revised: 01/14/2025] [Accepted: 03/04/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND In China Banxia Xiexin decoction (BXD) has been used in treating gastric cancer (GC) for thousands of years. BXD has been shown to reverse GC histopathology, but its chemical composition and action mechanism are still unknown.
AIM To investigate the mechanism of BXD against GC based on utilizing transcriptomics and proteomics techniques experiments.
METHODS Using the AGS cell line as the model group, the Cell Counting Kit-8 method and Annexin V-AbFluor™ were employed 488/propidium iodide double staining method was used to detect the levels of cell proliferation and apoptosis. Differential expression genes and differentially expressed proteins before and after BXD intervention were detected using RNA-seq and Pro DIA techniques. Key transcription factors were identified by enrichment and analysis using Metascape, and the key pathways were validated by western blot and reverse transcription PCR in vitro and in vivo experiments.
RESULTS BXD significantly inhibited the proliferation rate and migration rate of GC cells and promoted cell apoptosis. The comprehensive analysis of transcriptomics and proteomics showed that five transcription factors, namely phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, phosphoinositide-3-kinase regulatory subunit 1, AKT serine/threonine kinase 1, heat shock protein 90 alpha family class A member 1, and tumor protein p53, were key factors in BXD-mediated anti-cancer therapy and participated in the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway. In vitro experiments were conducted using LY294002, an inhibitor of the PI3K/AKT signaling pathway, to validate the expression of five transcription factors at the protein and mRNA levels. In vivo experiments have shown that BXD inhibits tumor growth and suppresses the expression of the PI3K/AKT signaling pathway.
CONCLUSION Transcriptomic and proteomic analysis showed that BXD inhibited tumor growth and slowed cancer progression by suppressing five factors in the PI3K/AKT signaling pathway, including phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, phosphoinositide-3-kinase regulatory subunit 1, and AKT serine/threonine kinase 1.
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Affiliation(s)
- Guo-Xiu Zu
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China
| | - Ji-Qin Tang
- School of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China
| | - Hai-Liang Huang
- School of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China
| | - Tao Han
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China
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Zhu L, Xie L, Wang Z, Li KL, Cai W. Mass spectrometry-based metabolomics reveal the effects and potential mechanism of isochlorogenic acid A in MC3T3-E1 cells. Front Mol Biosci 2025; 12:1518873. [PMID: 40201241 PMCID: PMC11975594 DOI: 10.3389/fmolb.2025.1518873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Accepted: 02/27/2025] [Indexed: 04/10/2025] Open
Abstract
Introduction The bioactive compound 3,5-DiCQA, derived from Duhaldea nervosa, has been traditionally utilized in folk remedies for bone fractures and osteoporosis. However, its therapeutic mechanisms remain unclear. Methods We employed UHPLC-Q Exactive Orbitrap MS-based cell metabolomics to investigate the molecular mechanisms of 3,5-DiCQA in MC3T3-E1 cells. Cell proliferation was assessed via MTT assay, differentiation by alkaline phosphatase (ALP) activity, and mineralization through alizarin red staining and cetylpyridinium chloride quantification. Metabolomic profiling compared drug-treated and control groups. Results Results from MTT assays demonstrated that 3,5-DiCQA significantly promoted cell proliferation at 100 μM. Alkaline phosphatase (ALP) assays and alizarin red staining revealed enhanced osteoblast differentiation and mineralization, respectively. Calcification deposition was significantly increased in the calcified stained cells by cetylpyridinium chloride quantization, indicating that 3,5-DiCQA can promote the mineralization of MC3T3-E1 cells. Metabolomic analysis identified key metabolic changes, including the downregulation of phytosphingosine and upregulation of sphinganine and citric acid. Discussion These findings suggest that 3,5-DiCQA promotes osteoblast proliferation, differentiation and mineralization through pathways such as sphingolipid metabolism, arginine and proline metabolism, mucin type O-glycan biosynthesis and the citrate cycle (TCA cycle). This study provides insights into the therapeutic potential of 3,5-DiCQA for osteoporosis and highlights the utility of metabolomics in elucidating traditional Chinese medicine (TCM).
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Affiliation(s)
- Lian Zhu
- School of Pharmaceutical Sciences, Sino-Pakistan Center on Traditional Chinese Medicine, Hunan University of Medicine, Huaihua, China
| | - Liu Xie
- Department of Pathology and Research Office of the School of Basic Medicine, Hunan University of Medicine, Huaihua, China
| | - Ziming Wang
- School of Pharmaceutical Sciences, Sino-Pakistan Center on Traditional Chinese Medicine, Hunan University of Medicine, Huaihua, China
| | - Kai-Lin Li
- School of Pharmaceutical Sciences, Sino-Pakistan Center on Traditional Chinese Medicine, Hunan University of Medicine, Huaihua, China
| | - Wei Cai
- School of Pharmaceutical Sciences, Sino-Pakistan Center on Traditional Chinese Medicine, Hunan University of Medicine, Huaihua, China
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Li T, Jiang H, Gong Y, Liao M, Jia Y, Chen J, Dai M, Yan Y, Lu X, Chen R, Li Y, Chen Y, Lin J, Li Y, Ding X. CHI3L1: a key driver in gastritis-to-cancer transformation. J Transl Med 2025; 23:349. [PMID: 40108688 PMCID: PMC11921547 DOI: 10.1186/s12967-025-06352-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Accepted: 03/05/2025] [Indexed: 03/22/2025] Open
Abstract
BACKGROUND Gastric cancer, recognized as one of the most lethal malignancies globally, progresses through a complex, multi-stage development. Elucidating the pathogenic mechanisms behind gastric carcinogenesis and identifying early diagnostic biomarkers are pivotal for decreasing the prevalence of gastric cancer. METHODS Using datasets on gastric cancer and its transformation from gastritis, we employed machine learning to create an early diagnostic model, identifying key genes and evaluating accuracy. We prioritized genes in the gastritis-to-cancer progression, identifying a central driver gene. Pathway analysis revealed its transformation role. Tissue microarrays and rat models validated the driver genes and networks, confirmed in cell and organoid models. We also identified cell types secreting CHI3L1 using single-cell RNA sequencing and multiplex immunohistochemistry, exploring their prognostic significance. RESULTS We identified 12 driver genes potentially involved in the gastritis-to-cancer transformation, with CHI3L1, MMP12, CXCL6, IDO1, and CCL20 emerging as the top five genes via a early gastric cancer diagnostic model. CHI3L1 was pinpointed as the central driver across the gastritis-to-cancer spectrum, with its upregulation, along with CD44, β-catenin, and c-Myc, noted in gastric precancerous lesions. In vitro and organoid studies revealed CHI3L1's role in activating the CD44-β-catenin pathway to induce malignancy. Furthermore, our findings indicate that fibroblasts and dendritic cells are the principal sources of CHI3L1 secretion, a factor that is associated with poor prognosis in gastric cancer. CONCLUSIONS This study highlights CHI3L1 as a key gene driving the progression from gastritis to gastric cancer, primarily by activating the CD44-β-catenin pathway, which enhances malignant cell traits. CHI3L1 is mainly secreted by fibroblasts and dendritic cells, and its high levels are linked to poor gastric cancer prognosis.
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Affiliation(s)
- Tao Li
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Huizhong Jiang
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Yucheng Gong
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Mengting Liao
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Yuanping Jia
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Jiena Chen
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Ming Dai
- MOE Key Laboratory of Membraneless Organelle and Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, 230027, China
| | - Yinan Yan
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Xinyu Lu
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Runhua Chen
- Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, China
| | - Yuan Li
- National Institute of Traditional Chinese Medicine Constitution and Preventive Treatment of Diseases, Beijing University of Chinese Medicine, Beijing, 100029, China
- Research Center for Spleen and Stomach Diseases of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Yan Chen
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Jie Lin
- National Institute of Traditional Chinese Medicine Constitution and Preventive Treatment of Diseases, Beijing University of Chinese Medicine, Beijing, 100029, China
- Research Center for Spleen and Stomach Diseases of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Yicong Li
- Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, China.
| | - Xia Ding
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China.
- Research Center for Spleen and Stomach Diseases of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.
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Wang L, Lian YJ, Dong JS, Liu MK, Liu HL, Cao ZM, Wang QN, Lyu WL, Bai YN. Traditional Chinese medicine for chronic atrophic gastritis: Efficacy, mechanisms and targets. World J Gastroenterol 2025; 31:102053. [PMID: 40061592 PMCID: PMC11886037 DOI: 10.3748/wjg.v31.i9.102053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 12/06/2024] [Accepted: 01/21/2025] [Indexed: 02/18/2025] Open
Abstract
Chronic atrophic gastritis (CAG) is an important stage of precancerous lesions of gastric cancer. Effective treatment and regulation of CAG are essential to prevent its progression to malignancy. Traditional Chinese medicine (TCM) has shown multi-targeted efficacy in CAG treatment, with advantages in enhancing gastric mucosal barrier defense, improving microcirculation, modulating inflammatory and immune responses, and promoting lesion healing, etc. Clinical studies and meta-analyses indicate that TCM provides significant benefits, with specific Chinese herbal compounds and monomers demonstrating protective effects on the gastric mucosa through mechanisms including anti-inflammation, anti-oxidation, and regulation of cellular proliferation and apoptosis, etc. Finally, it is pointed out that the efficacy of TCM in the treatment of CAG requires standardized research and unified standards, and constantly clarifies and improves the evaluation criteria of each dimension of gastric mucosal barrier function.
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Affiliation(s)
- Li Wang
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Yan-Jie Lian
- Division of Cardiovascular, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China
| | - Jin-Sheng Dong
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Ming-Kun Liu
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Hong-Liang Liu
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Zheng-Min Cao
- Department of Infectious Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Qing-Nan Wang
- Department of Dermatology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Wen-Liang Lyu
- Department of Infectious Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Yu-Ning Bai
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
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Jiang Q, Fan G, Wu K. Potential Action Mechanism of Erianin in Relieving MNNG-triggered Chronic Atrophic Gastritis. Cell Biochem Biophys 2025; 83:1035-1044. [PMID: 39298066 DOI: 10.1007/s12013-024-01536-x] [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: 09/07/2024] [Indexed: 09/21/2024]
Abstract
Chronic atrophic gastritis (CAG) is a critical initial step in gastric cancer tumorigenesis accompanied by high malignancy. Erianin has been proposed as a promising agent in treating precancerous lesions of gastric cancer. Considering that little work has been implemented concerning the specific role and possible regulatory mechanism of Erianin in CAG, the goal of the study is to disclose the effects and mechanism of erianin on the malignant transformation in the process of CAG. CAG cell model was generated in human gastric epithelium GES-1 cells induced by Nmethyl-N'-nitro-N-nitrosoguanidine (MNNG). CCK-8 method determined cell viability. ELISA and corresponding assay kits severally appraised the contents of inflammatory cytokines and oxidative stress markers. Cellular reactive oxygen species (ROS) formation was measured by flow cytometry analysis using DCFH-DA probe. GFP-LC3 immunofluorescence staining and Western blotting evaluated autophagy. Also, Western blotting analyzed the expression of components in mitogen activated protein kinase (MAPK)/mechanistic target of rapamycin (mTOR) signaling. The results manifested that MNNG treatment diminished the viability and autophagy whereas intensified the inflammation and oxidative stress in GES-1 cells, which were all reversed by Erianin. Besides, Erianin blocked mTOR/MAPK signaling in MNNG-exposed GES-1 cells. Autophagy inhibitor 3-methyladenine (3-MA) or p38 MAPK agonist asiatic acid partially counteracted the protection elicited by Erianin against viability loss, inflammatory reaction as well as oxidative stress in MNNG-induced GES-1 cells. Combined with the findings, Erianin might mediate autophagy to improve MNNG-elicited CAG via MAPK/mTOR signaling.
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Affiliation(s)
- Qianqian Jiang
- Traditional Chinese Medicine Department, Dongying People's Hospital (Dongying Hospital of Shandong Provincial Hospital Group), Dongying, Shandong, 257091, China
| | - Guoxia Fan
- Traditional Chinese Medicine Department, Dongying People's Hospital (Dongying Hospital of Shandong Provincial Hospital Group), Dongying, Shandong, 257091, China
| | - Kaiwei Wu
- Traditional Chinese Medicine Department, Dongying People's Hospital (Dongying Hospital of Shandong Provincial Hospital Group), Dongying, Shandong, 257091, China.
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Duraisamy R, Veerasamy V, Balakrishnan V, Jawaharlal S, Subramani S, Sathiavakoo VA. Exploring anticancer potential of betanin in DMBA-induced oral squamous cell carcinoma: an in silico and experimental study. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025:10.1007/s00210-025-03909-2. [PMID: 40009172 DOI: 10.1007/s00210-025-03909-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Accepted: 02/10/2025] [Indexed: 02/27/2025]
Abstract
In addition to being able to fight cancer, betanin (BTN) has amazing natural antioxidant and peroxy-radical scavenging properties. 7,12-Dimethylbenz[a]anthracene (DMBA) can impair the activities of enzymes accountable for breaking down xenobiotics and can also cause lipid peroxidation. The study's goal was to find out if betanin could protect against these problems. We determined 100% tumor incidence, abnormal tumor volume, inclined tumor burden, and deduced body weight in DMBA-induced hamsters. We observed diminished lipid peroxidation and enzymatic and nonenzymatic antioxidant activities in DMBA-induced hamsters. The histological study showed that the hamster that receives only DMBA undergoes hyperkeratosis, epithelial hyperplasia, dysplasia, and well-differentiated oral squamous cell carcinoma (OSCC). The hamsters received three different dosages of BTN (10, 20, and 40 mg/kg b.w.) via intragastric intubation for 14 weeks, on alternate days of DMBA painting. The levels of antioxidants, xenobiotic enzymes, and lipid peroxidation (LPO) were significantly restored and inhibited tumor development in a dose-dependent manner. The molecular docking study found high levels of binding affinity in Bax (PDB ID: 2K7W), Caspase-3 (PDB ID: 4JJ8), Caspase-9 (PDB ID: 2AR9), PI3K (PDB ID: 5XGI), AKT (PDB ID: 6BUU), p53 (PDB ID: 1YCS), SMAD-2 (PDB ID: 1DEV), SMAD-4 (PDB ID: 1YGS), SMAD-7 (PDB ID: 2DJY), TGFβ-I (PDB ID: 1PY5), and TGFβ-II (PDB ID: 1M9Z). So, therefore, in vivo and in silico studies were providing prominent anticancer activity of betanin against DMBA-induced oral cancer.
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Affiliation(s)
- Ramachandhiran Duraisamy
- Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Chidambaram, Annamalainagar, 608002, Tamil Nadu, India
| | - Vinothkumar Veerasamy
- Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Chidambaram, Annamalainagar, 608002, Tamil Nadu, India.
| | - Vaitheeswari Balakrishnan
- Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Chidambaram, Annamalainagar, 608002, Tamil Nadu, India
| | - Saranya Jawaharlal
- Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Chidambaram, Annamalainagar, 608002, Tamil Nadu, India
| | - Srinivasan Subramani
- Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Chidambaram, Annamalainagar, 608002, Tamil Nadu, India
- Research Department of Biochemistry, Government Arts College for Women, Krishnagiri, Tamil Nadu, India
| | - Vigil Anbiah Sathiavakoo
- Central Animal House Government Medical College and Hospital Cuddalore, Chidambaram, Annamalainagar, 608002, Tamil Nadu, India
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Zhang Y, Yang K, Bai J, Chen J, Ou Q, Zhou W, Li X, Hu C. Single-cell transcriptomics reveals the multidimensional dynamic heterogeneity from primary to metastatic gastric cancer. iScience 2025; 28:111843. [PMID: 39967875 PMCID: PMC11834116 DOI: 10.1016/j.isci.2025.111843] [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: 07/01/2024] [Revised: 12/12/2024] [Accepted: 12/18/2024] [Indexed: 02/20/2025] Open
Abstract
Reprogramming of the tumor microenvironment (TME) plays a critical role in gastric cancer (GC) progression and metastasis. However, the multidimensional features between primary tumors and organ-specific metastases remain poorly understood. In this study, we characterized the dynamic heterogeneity of GC from primary to metastatic stages. We identified seven major cell types and 27 immune and stromal subsets. Immune cells decreased, while immunosuppressive cells increased in ovarian and peritoneal metastases. A 30-gene signature for ovarian metastasis was validated in GC cohorts. Additionally, critical ligand-receptor interactions, including LGALS9-MET in liver metastasis and PVR-TIGIT in lymph node metastasis, were identified as potential therapeutic targets. Furthermore, CLOCK, a transcription factor, was associated with poor prognosis and influenced immune cell interactions and migration. Collectively, this study provides valuable insights into TME dynamics in GC and highlights potential avenues for targeted therapies.
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Affiliation(s)
- Yunpeng Zhang
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, Heilongjiang, China
| | - Kuan Yang
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, Heilongjiang, China
| | - Jing Bai
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, Heilongjiang, China
| | - Jing Chen
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, Heilongjiang, China
| | - Qi Ou
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, Heilongjiang, China
| | - Wenzhe Zhou
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, Heilongjiang, China
| | - Xia Li
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, Heilongjiang, China
| | - Congxue Hu
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, Heilongjiang, China
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Liang L, He C, Han X, Liu J, Yang L, Chang F, Zhang Y, Lin J. Zuojin Pill Alleviates Precancerous Lesions of Gastric Cancer by Modulating the MEK/ERK/c-Myc Pathway: An Integrated Approach of Network Pharmacology, Molecular Dynamics Simulation, and Experimental Validation. Drug Des Devel Ther 2024; 18:5905-5929. [PMID: 39679136 PMCID: PMC11646374 DOI: 10.2147/dddt.s487371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Accepted: 11/21/2024] [Indexed: 12/17/2024] Open
Abstract
Background Precancerous lesions of gastric cancer (PLGC) represent critical stages in gastric cancer progression, with a high risk of malignancy. Current treatments, such as Helicobacter pylori eradication, show limited efficacy in reversing precancerous molecular changes. Zuojin Pill (ZJP), a traditional Chinese medicine, has demonstrated potential for treating digestive disorders and may offer a promising approach for PLGC intervention. Objective This study aims to investigate the therapeutic effects and mechanisms of ZJP in treating PLGC, focusing on its active components, target pathways, and molecular interactions. By using advanced analytical techniques, we provide a scientific foundation for ZJP's potential application in early gastric cancer intervention. Methods Using ultra-high performance liquid chromatography-quadrupole orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap HRMS), we identified active components in ZJP. A network pharmacology approach was then applied to construct a "ZJP-compound-target-disease" network. Molecular docking and molecular dynamics simulations were conducted to analyze the stability and interactions of the main active components of ZJP with core protein targets in PLGC. Animal experiments were used to validate significant targets and pathways in vivo. Results Tangeritin, Isorhamnetin, Caffeic Acid, Azelaic Acid, and Adenosine were identified as the main active components of ZJP in the treatment of PLGC, with key targets including PIK3R1, MAPK3, SRC, JAK2, STAT3, and PIK3CA. Molecular docking and molecular dynamics simulations further confirmed the relationship between compounds and target proteins. The potential molecular mechanism of ZJP predicted by network pharmacology analysis was confirmed in PLGC rats. ZJP downregulated IL-6, TNF-α, c-myc, p-MEK1 and p-ERK1/2, effectively reversing the progression of PLGC. Conclusion ZJP can reverse MNNG-induced PLGC, potentially through inhibition of the MEK/ERK/c-myc pathway and regulation of cellular proliferation and apoptosis.
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Affiliation(s)
- Lan Liang
- The First Clinical Medical School, Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of China
- College of Nursing, Shaanxi Energy Institute, Xianyang, People’s Republic of China
| | - Chenming He
- LongHua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China
| | - Xue Han
- Xijing 986 Hospital Department, Air Force Medical University, Xian, People’s Republic of China
| | - Jia Liu
- School of Basic Medical Sciences, Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of China
| | - Liuhong Yang
- School of Basic Medical Sciences, Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of China
| | - Fengjiao Chang
- School of Nursing, Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of China
| | - Yami Zhang
- The Fifth Oncology Department, Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of China
| | - Jie Lin
- School of Basic Medical Sciences, Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of China
- Shaanxi Provincial Key Laboratory of TCM Constitution and Disease Prevention, Xianyang, People’s Republic of China
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Tang L, Ruan Y, Wang B, Zhang M, Xue J, Wang T. Erianin inhibits the progression of DDP-resistant lung adenocarcinoma by regulating the Wnt/β-catenin pathway and activating the caspase-3 for apoptosis in vitro and in vivo. Hereditas 2024; 161:48. [PMID: 39605083 PMCID: PMC11600767 DOI: 10.1186/s41065-024-00351-x] [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: 09/12/2024] [Accepted: 11/19/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND Platinum-based chemotherapy is one of the main treatments for lung adenocarcinoma (LUAD). However, the toxic side effects and drug resistance of chemotherapeutic drugs on normal cells are still a thorny problem in clinical treatment. Dendrobium is one of the three largest genera of Orchidaceous family, which has ornamental and medicinal value. Dendrobium is mainly distributed in the tropics and subtropics of South Asia, Oceania and other regions, with 1547 species of Dendrobium currently known. In China, "Shi hu" and "Tie pi shi hu" are well-known traditional medicines and have been included in the Chinese Pharmacopoeia (Editorial Board of Chinese Pharmacopoeia, 2020). Erianin is a natural product isolated from Dendrobium and is considered as a potential anticancer molecule due to its remarkable anti-tumor effects through various mechanisms, among which induced cancer cell apoptosis, inhibited invasion and migration. This study preliminarily explored the mechanism of Erianin inhibiting the progression of cisplatin (DDP) resistant LUAD in vivo and in vitro. METHODS The effect of Erianin on the proliferation of DDP-resistant LUAD cells was detected by CCK-8 assay, wound healing assay and cloning assay. Transwell assay was used to evaluate the effect of Erianin on cell invasion and migration. The changes of cell cycle and apoptosis were detected by flow cytometry and TUNEL assay. Finally, the effects of Erianin on cell function and signaling pathway-related protein expression in vivo and in vitro were examined based on the enrichment analysis. RESULTS Erianin could inhibit the proliferation, invasion and migration, induce apoptosis, altered cell cycle of DDP-resistant LUAD cells, and reverse the resistance to DDP. Western blotting results showed that Erianin exerted its anti-tumor effects by regulating the Wnt/β-catenin cascade in DDP-resistant LUAD cells. CONCLUSION Erianin may exerted its anti-tumor effect in DDP-resistant LUAD cells by regulating the Wnt3/β-Catenin/Survivin/Bcl-2/Caspase-3/Cyclin D1 axis.
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Affiliation(s)
- Lingxue Tang
- Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Yiling Ruan
- Department of General practice, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Beibei Wang
- Department of General practice, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Mingjun Zhang
- Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Jie Xue
- Department of General Practice, Suixi County Hospital, Huaibei, Anhui, China.
| | - Tong Wang
- Department of General practice, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
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Liu R, Qiu M, Deng X, Zhang M, Gao Z, Wang Y, Mei H, Zhai M, Zhang Q, Hao J, Yang Z, Wang H. Erianin inhibits the progression of pancreatic cancer by directly targeting AKT and ASK1. Cancer Cell Int 2024; 24:348. [PMID: 39456094 PMCID: PMC11515188 DOI: 10.1186/s12935-024-03533-9] [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: 06/14/2024] [Accepted: 10/13/2024] [Indexed: 10/28/2024] Open
Abstract
BACKGROUND Pancreatic cancer is a malignant tumor of the digestive tract with a high mortality rate. Erianin has antitumor activity, but the regulatory targets and mechanism of action in pancreatic cancer are unclear. The objective of this study was to evaluate the anti-pancreatic cancer activity of Erianin and explore its underlying mechanisms. METHODS A network pharmacology approach was used to investigate the mechanism of action of Erianin in pancreatic cancer cells. Cell proliferation was analyzed using CCK8, colony-formation, and EdU proliferation assays. Cell migration was evaluated through wound healing and transwell assays, as well as determination of the protein expression levels of EMT markers and β-catenin. Apoptosis and the cell cycle were measured using flow cytometry and JC-1 staining, respectively. The protein expression levels of p-Rb, CyclinB1, P21, Cleaved-PARP, and Cleaved-Caspase3 were assessed using western blotting. RNA sequencing (RNA-seq) and bioinformatics analyses were performed to elucidate the mechanism underlying the action of Erianin in pancreatic cancer. Western blotting was used to examine the expression levels of key proteins in the AKT, JNK, and p38 MAPK signaling pathways. Molecular docking and CETSA were used to test hypotheses. The tumor-suppressive ability of Erianin in vivo was assessed using a tumor-bearing assay in nude mice. RESULTS Network pharmacology revealed that Erianin inhibited pancreatic cancer through multiple pathways. Erianin significantly inhibited pancreatic cancer cell proliferation and migration while promoting intracellular ROS and inducing apoptosis. Mechanistically, Erianin inhibited pancreatic cancer cell proliferation by regulating the AKT/FOXO1 and ASK1/JNK/p38 MAPK signaling pathways. In vivo experiments showed that Erianin inhibited subcutaneous tumor growth and promoted tumor tissue apoptosis in nude mice. CONCLUSIONS The component-target-pathway network revealed that Erianin exerted anti-cancer effects through multiple components, targets, and pathways. Erianin inhibited the proliferation and migration of pancreatic cancer cells and induced apoptosis through the AKT/FOXO1 and ASK1/JNK/p38 MAPK signaling pathways. These results indicate that Erianin is a promising agent for pancreatic cancer treatment.
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Affiliation(s)
- Ruxue Liu
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
- Department of Oncology, Tianjin Union Medical Center of Nankai University, Tianjin, 300121, China
- Tianjin Cancer Institute of Integrative Traditional Chinese and Western Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, 300121, China
| | - Minghan Qiu
- Department of Oncology, Tianjin Union Medical Center of Nankai University, Tianjin, 300121, China.
- The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, 300121, China.
- Tianjin Cancer Institute of Integrative Traditional Chinese and Western Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, 300121, China.
- School of Medicine, Nankai University, Tianjin, 300121, China.
| | - Xinxin Deng
- Department of Oncology, Tianjin Union Medical Center of Nankai University, Tianjin, 300121, China
- Tianjin Cancer Institute of Integrative Traditional Chinese and Western Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, 300121, China
| | - Meng Zhang
- School of Medicine, Nankai University, Tianjin, 300121, China
| | - Zhanhua Gao
- School of Medicine, Nankai University, Tianjin, 300121, China
| | - Yayun Wang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
- Department of Oncology, Tianjin Union Medical Center of Nankai University, Tianjin, 300121, China
| | - Hanwei Mei
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Mengting Zhai
- School of Medicine, Nankai University, Tianjin, 300121, China
| | - Qiaonan Zhang
- School of Medicine, Nankai University, Tianjin, 300121, China
| | - Jie Hao
- Tianjin Cancer Institute of Integrative Traditional Chinese and Western Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, 300121, China
- Department of Thyroid and Breast Surgery, Tianjin Key Laboratory of General Surgery in Construction, Tianjin Union Medical Center of Nankai University, Tianjin, 300121, China
| | - Zhen Yang
- Department of Laboratory, Tianjin Union Medical Center of Nankai University, Tianjin, 300121, China.
- The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, 300121, China.
- Tianjin Cancer Institute of Integrative Traditional Chinese and Western Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, 300121, China.
| | - Huaqing Wang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
- Department of Oncology, Tianjin Union Medical Center of Nankai University, Tianjin, 300121, China.
- The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, 300121, China.
- Tianjin Cancer Institute of Integrative Traditional Chinese and Western Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, 300121, China.
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Zu GX, Sun KY, Liu XJ, Tang JQ, Huang HL, Han T. Banxia xiexin decoction prevents the development of gastric cancer. World J Clin Oncol 2024; 15:1293-1308. [DOI: 10.5306/wjco.v15.i10.1293] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 08/09/2024] [Accepted: 08/23/2024] [Indexed: 09/29/2024] Open
Abstract
BACKGROUND In China banxia xiexin decoction (BXD) has been used in treating gastric cancer (GC) for thousands of years and BXD has a good role in reversing GC histopathology, but its chemical composition and action mechanism are still unknown.
AIM To investigate the mechanism of action of BXD against GC based on transcriptomics, network pharmacology, in vivo and in vitro experiments.
METHODS The transplanted tumor model was prepared, and the nude mouse were pathologically examined after administration, and hematoxylin-eosin staining was performed. The active ingredients of BXD were quality controlled and identified using ultra-performance liquid chromatography tandem quadrupole electrostatic field orbitrap mass spectrometry (UPLC-Q-Orbitrap MS/MS), and traditional Chinese medicines systems pharmacology platform, drug bank and the Swiss target prediction platform to predict the relevant targets, the differentially expressed genes (DEGs) of GC were screened by RNA-seq sequencing, and the overlapping targets were analyzed to obtain the key targets and pathways. Cell Counting Kit-8, apoptosis assay, cell migration and Realtime fluorescence quantitative polymerase chain reaction were used for in vitro experiments.
RESULTS All dosing groups inhibited the growth of transplanted tumors in laboratory-bred strain nude, with the capecitabine group and the BXD medium-dose group being the best. A total of 29 compounds and 859 potential targets in BXD were identified by UPLC-Q-Orbitrap MS/MS and network pharmacology, RNA-seq sequencing found 4767 GC DEGs, which were combined with network pharmacology and analyzed 246 potential therapeutic targets were obtained and pathway results showed that BXD may against GC through the Phosphoinositide 3-kinase (PI3K)/protein kinase B (AKt) signaling pathway. In vitro cellular experiments confirmed that BXD-containing serum and LY294002 could inhibit the proliferation of GC cells, promote apoptosis, and inhibit the migration of GC cells by decreasing the expression of EGFR, PIK3CA, IL6, BCL2 and AKT1 in the PI3K-Akt pathway in MGC-803 expression.
CONCLUSION BXD has the effect of inhibiting tumor growth rate and delaying the development of GC. Its mechanism of action may be related to the regulation of PI3K-Akt signaling pathway.
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Affiliation(s)
- Guo-Xiu Zu
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China
| | - Ke-Yun Sun
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China
| | - Xi-Jian Liu
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China
| | - Ji-Qin Tang
- School of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China
| | - Hai-Liang Huang
- School of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China
| | - Tao Han
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China
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13
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Ni J, Chen X, Chen N, Yan Y, Wu Y, Li B, Huang H, Tong H, Liu Y, Dai N. Erianin alleviates LPS-induced acute lung injury via antagonizing P-selectin-mediated neutrophil adhesion function. JOURNAL OF ETHNOPHARMACOLOGY 2024; 331:118336. [PMID: 38750983 DOI: 10.1016/j.jep.2024.118336] [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: 03/23/2024] [Revised: 04/28/2024] [Accepted: 05/10/2024] [Indexed: 05/19/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Dendrobium officinale Kimura et Migo, known as "Tiepi Shihu" in traditional Chinese medicine, boasts an extensive history of medicinal use documented in the Chinese Pharmacopoeia. "Shen Nong Ben Cao Jing" records D. officinale as a superior herbal medicine for fortifying "Yin" and invigorating the five viscera. Erianin, a benzidine compound, emerges as a prominent active constituent derived from D. officinale, with the pharmacological efficacy of D. officinale closely linked to the anti-inflammatory properties of erianin. AIM OF THE STUDY Acute lung injury (ALI) is a substantial threat to global public health, while P-selectin stands out as a promising novel target for treating acute inflammatory conditions. This investigation aims to explore the therapeutic potential of erianin in ALI treatment and elucidate the underlying mechanisms. EXPERIMENTAL DESIGN The effectiveness of erianin in conferring protection against ALI was investigated through comprehensive histopathological and biochemical analyses of lung tissues and bronchoalveolar lavage fluid (BALF) in an in vivo model of LPS-induced ALI in mice. The impact of erianin on fMLP-induced neutrophil chemotaxis was quantitatively assessed using the Transwell and Zigmond chamber, respectively. To determine the therapeutic target of erianin and elucidate their binding capability, a series of sophisticated assays were employed, including drug affinity responsive target stability (DARTS) assay, cellular thermal shift assay (CETSA), and molecular docking analyses. RESULTS Erianin demonstrated a significant alleviation of LPS-induced acute lung injury, characterized by reduced total cell and neutrophil counts and diminished total protein contents in BALF. Moreover, erianin exhibited a capacity to decrease proinflammatory cytokine production in both lung tissues and BALF. Notably, erianin effectively suppressed the activation of NF-κB signaling in the lung tissues of LPS- challenged mice; however, it did not exhibit in vitro inhibitory effects on inflammation in LPS-induced human pulmonary microvascular endothelial cells (HPMECs). Additionally, erianin blocked the adhesion and rolling of neutrophils on HPMECs. While erianin did not influence endothelial P-selectin expression or cytomembrane translocation, it significantly reduced the ligand affinity between P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1). CONCLUSIONS Erianin inhibits P-selectin-mediated neutrophil adhesion to activated endothelium, thereby alleviating ALI. The present study highlights the potential of erianin as a promising lead for ALI treatment.
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Affiliation(s)
- Jiangwei Ni
- Department of Thoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China
| | - Xiaohai Chen
- Department of Pharmacy, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325200, PR China
| | - Nengfu Chen
- Department of Thoracic Surgery, The Affiliated Cangnan Hospital of Wenzhou Medical University, Wenzhou, 325800, PR China
| | - Yawei Yan
- College of Pharmacy, Wenzhou Medical University, Wenzhou, 325000, PR China
| | - Yu Wu
- Zhejiang Provincial Key Laboratory for Water Environment and Marine Biological Resources Protection, College of Life and Environmental Science, Wenzhou University, Wenzhou, 325000, PR China
| | - Boyang Li
- Zhejiang Provincial Key Laboratory for Water Environment and Marine Biological Resources Protection, College of Life and Environmental Science, Wenzhou University, Wenzhou, 325000, PR China
| | - Hui Huang
- Department of Pharmacy, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou, 325000, PR China
| | - Haibin Tong
- Zhejiang Provincial Key Laboratory for Water Environment and Marine Biological Resources Protection, College of Life and Environmental Science, Wenzhou University, Wenzhou, 325000, PR China; State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Beijing, 100700, PR China.
| | - Yu Liu
- Department of Thoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China.
| | - Ningfeng Dai
- Department of Thoracic Surgery, The Affiliated Cangnan Hospital of Wenzhou Medical University, Wenzhou, 325800, PR China.
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14
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Wu Y, Wang Y, Liu H, Hu Q, Xie Y, Nan X, He H, Liu Y. Mechanism of apoptosis in oral squamous cell carcinoma promoted by cardamonin through PI3K/AKT signaling pathway. Sci Rep 2024; 14:20802. [PMID: 39242879 PMCID: PMC11379709 DOI: 10.1038/s41598-024-71817-1] [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: 05/22/2024] [Accepted: 08/30/2024] [Indexed: 09/09/2024] Open
Abstract
Currently, surgical resection remains the primary approach for treating oral squamous cell carcinoma (OSCC), with limited options for effective drug therapy. Cardamonin, a principal compound derived from Myristica fragrans of the Zingiberaceae family, has garnered attention for its potential to suppress the onset and progression of various malignancies encompassing breast cancer, hepatocellular carcinoma, and ovarian cancers. Nevertheless, the involvement of cardamonin in the treatment of OSCC and its underlying mechanisms are yet to be elucidated. This research explored the possible target of cardamonin in treating OSCC via network pharmacological analysis. Subsequently, this research investigated the impact of cardamonin on OSCC cells via in vitro experiments, revealing its capacity to impede the migration, proliferation, and invasion of OSCC cells. Additionally, western blotting analysis demonstrated that cardamonin facilitates apoptosis by regulating the PI3K/AKT pathway. The findings suggest that MMP9 and the PI3K/AKT signaling pathway may serve as the target and pathway of cardamonin in treating OSCC. To summarize, the research findings suggest that cardamonin may facilitate apoptosis in OSCC cells by inhibition of PI3K/AKT pathway activation. These outcomes offer a theoretical basis for the utilization of cardamonin as a natural drug for treating OSCC.
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Affiliation(s)
- Yuehan Wu
- Department of Stomatology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
- Department of Stomatology, North Sichuan Medical College, Nanchong, China
| | - Yapei Wang
- Department of Stomatology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
- Department of Stomatology, North Sichuan Medical College, Nanchong, China
| | - Han Liu
- Department of Stomatology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
- Department of Stomatology, North Sichuan Medical College, Nanchong, China
| | - Qiannan Hu
- Department of Stomatology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Yuqi Xie
- Department of Stomatology, North Sichuan Medical College, Nanchong, China
| | - Xiaoxu Nan
- Department of Stomatology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
- Department of Stomatology, North Sichuan Medical College, Nanchong, China
| | - Huan He
- Department of Stomatology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Ying Liu
- Department of Stomatology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
- Department of Stomatology, North Sichuan Medical College, Nanchong, China.
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15
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Zhang M, Zhong J, Song Z, Xu Q, Chen Y, Zhang Z. Regulatory mechanisms and potential therapeutic targets in precancerous lesions of gastric cancer: A comprehensive review. Biomed Pharmacother 2024; 177:117068. [PMID: 39018877 DOI: 10.1016/j.biopha.2024.117068] [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: 05/10/2024] [Revised: 06/27/2024] [Accepted: 06/27/2024] [Indexed: 07/19/2024] Open
Abstract
Precancerous lesions of gastric cancer (PLGC) represent a critical pathological stage in the transformation from normal gastric mucosa to gastric cancer (GC). The global incidence of PLGC has been rising over the past few decades, with a trend towards younger onset ages. Increasing evidence suggests that early prevention and treatment of PLGC can effectively reverse the malignant development of gastric mucosal epithelial cells. However, there is currently a lack of effective therapeutic drugs and methods. Recent years have witnessed substantial advancements in PLGC research, with the elucidation of novel regulatory mechanisms offering promising avenues for clinical intervention and drug development. This review aims to delineate potential targets for early prevention and diagnosis of GC while exploring innovative approaches to PLGC management. This article focuses on elucidating the regulatory mechanisms of the inflammatory microenvironment, bile acids (BA), glycolysis, autophagy, apoptosis, ferroptosis, and cellular senescence. We pay particular attention to potential therapeutic targets for PLGC, with the goal of providing insights and theoretical basis for clinical research on PLGC.
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Affiliation(s)
- Maofu Zhang
- Clinical College of Traditional Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, China
| | - Jialin Zhong
- Clinical College of Traditional Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, China
| | - Zhongyang Song
- Department of Oncology, Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu 730020, China
| | - Qian Xu
- Clinical College of Traditional Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, China
| | - Yuchan Chen
- Clinical College of Traditional Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, China
| | - Zhiming Zhang
- Department of Oncology, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou, Gansu 730050, China.
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16
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Wei X, Liu Q, Liu L, Wang D, Liu J, Zhu Q, Xu Z, Chen Q, Xu W. Discovery of the Natural Bibenzyl Compound Erianin in Dendrobium Inhibiting the Growth and EMT of Gastric Cancer through Downregulating the LKB1-SIK2/3-PARD3 Pathway. Int J Mol Sci 2024; 25:7973. [PMID: 39063214 PMCID: PMC11277420 DOI: 10.3390/ijms25147973] [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: 05/26/2024] [Revised: 07/11/2024] [Accepted: 07/17/2024] [Indexed: 07/28/2024] Open
Abstract
Erianin, a bibenzyl compound found in dendrobium extract, has demonstrated broad anticancer activity. However, its mechanism of action in gastric cancer (GC) remains poorly understood. LKB1 is a tumor-suppressor gene, and its mutation is an important driver of various cancers. Yet some studies have reported contradictory findings. In this study, we combined bioinformatics and in vitro and in vivo experiments to investigate the effect and potential mechanism of Erianin in the treatment of GC. The results show that LKB1 was highly expressed in patients' tumor tissues and GC cells, and it was associated with poor patient prognosis. Erianin could promote GC cell apoptosis and inhibit the scratch repair, migration, invasion, and epithelial-mesenchymal transition (EMT) characteristics. Erianin dose-dependently inhibited the expression of LKB1, SIK2, SIK3, and PARD3 but had no significant effect on SIK1. Erianin also inhibited tumor growth in CDX mice model. Unexpectedly, 5-FU also exhibited a certain inhibitory effect on LKB1. The combination of Erianin and 5-FU significantly improved the anti-tumor efficacy of 5-FU in the growth of GC cells and xenograft mouse models. In summary, Erianin is a potential anti-GC compound that can inhibit GC growth and EMT properties by targeting the LKB1-SIK2/3-PARD3-signaling axis. The synergistic effect of Erianin and 5-FU suggests a promising therapeutic strategy for GC treatment.
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Affiliation(s)
- Xin Wei
- Institute of Intelligent Machines, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China; (X.W.); (Q.Z.); (Q.C.)
- Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China; (Q.L.); (L.L.); (D.W.); (J.L.); (Z.X.)
| | - Qunshan Liu
- Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China; (Q.L.); (L.L.); (D.W.); (J.L.); (Z.X.)
| | - Liu Liu
- Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China; (Q.L.); (L.L.); (D.W.); (J.L.); (Z.X.)
| | - Dan Wang
- Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China; (Q.L.); (L.L.); (D.W.); (J.L.); (Z.X.)
| | - Jiajia Liu
- Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China; (Q.L.); (L.L.); (D.W.); (J.L.); (Z.X.)
| | - Qizhi Zhu
- Institute of Intelligent Machines, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China; (X.W.); (Q.Z.); (Q.C.)
- Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China; (Q.L.); (L.L.); (D.W.); (J.L.); (Z.X.)
| | - Ziming Xu
- Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China; (Q.L.); (L.L.); (D.W.); (J.L.); (Z.X.)
| | - Qi Chen
- Institute of Intelligent Machines, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China; (X.W.); (Q.Z.); (Q.C.)
- Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China; (Q.L.); (L.L.); (D.W.); (J.L.); (Z.X.)
| | - Weiping Xu
- Institute of Intelligent Machines, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China; (X.W.); (Q.Z.); (Q.C.)
- Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China; (Q.L.); (L.L.); (D.W.); (J.L.); (Z.X.)
- Anhui Provincial Key Laboratory of Tumor Immunotherapy and Nutrition Therapy, Hefei 230001, China
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17
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Chen J, He Q, Jin J. Targeting dendritic cell activation: the therapeutic impact of paeoniflorin in cortosteroid-dependent dermatitis management. Arch Dermatol Res 2024; 316:348. [PMID: 38849562 DOI: 10.1007/s00403-024-03002-3] [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: 04/11/2024] [Revised: 04/11/2024] [Accepted: 04/26/2024] [Indexed: 06/09/2024]
Abstract
This study investigates the mechanism through which paeoniflorin inhibits TSLP expression to regulate dendritic cell activation in corticosteroid-dependent dermatitis treatment. Utilizing databases like TCMSP, we identified paeoniflorin's components, targets, and constructed networks. Molecular docking and gene enrichment analysis helped pinpoint key targets and pathways affected by paeoniflorin. In vitro and in vivo models were used to study CD80, CD86, cytokines, T-cell activation, skin lesions, histopathological changes, TSLP, CD80, and CD86 expression. Our study revealed paeoniflorin's active constituent targeting IL-6 in corticosteroid-dependent dermatitis. In vitro experiments demonstrated reduced TSLP expression, CD80, CD86, and cytokine secretion post-paeoniflorin treatment. In vivo, paeoniflorin significantly decreased skin lesion severity, cytokine levels, TSLP, CD80, and CD86 expression. The study highlights paeoniflorin's efficacy in inhibiting TSLP expression and suppressing dendritic cell activation in corticosteroid-dependent dermatitis, suggesting its potential as a therapeutic intervention. Additionally, it offers insights into the complex molecular mechanisms underlying paeoniflorin's anti-inflammatory properties in treating corticosteroid-dependent dermatitis.
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Affiliation(s)
- Jinjin Chen
- Department of Dermatology, Hubei Provincial Hospital of Traditional Chinese Medicine, No. 4 Huayuanshan, Wuchang District, Wuhan, Hubei Province, 430061, China
| | - Qi He
- Department of Dermatology, Hubei Provincial Hospital of Traditional Chinese Medicine, No. 4 Huayuanshan, Wuchang District, Wuhan, Hubei Province, 430061, China
| | - Jing Jin
- Department of Dermatology, Hubei Provincial Hospital of Traditional Chinese Medicine, No. 4 Huayuanshan, Wuchang District, Wuhan, Hubei Province, 430061, China.
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Wu CY, Guo YY, Ma ZY, Zhou J, Long F, Shen H, Xu JD, Zhou SS, Huo JG, Hu CH, Li SL. Rationality of the ethanol precipitation process in modern preparation production of Zishui-Qinggan decoction evaluated by integrating UPLC-QTOF-MS/MS-based chemical profiling/serum pharmacochemistry and network pharmacology. PHYTOCHEMICAL ANALYSIS : PCA 2024; 35:733-753. [PMID: 38219286 DOI: 10.1002/pca.3325] [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: 10/25/2023] [Revised: 12/20/2023] [Accepted: 12/22/2023] [Indexed: 01/16/2024]
Abstract
INTRODUCTION Zishui-Qinggan decoction (ZQD) is a classical traditional Chinese medicine formula (TCMF) for alleviating menopausal symptoms (MPS) induced by endocrine therapy in breast cancer patients. In the production of TCMF modern preparations, ethanol precipitation (EP) is a commonly but not fully verified refining process. OBJECTIVES Chemical profiling/serum pharmacochemistry and network pharmacology approaches were integrated for exploring the rationality of the EP process in the production of ZQD modern preparations. MATERIAL AND METHODS Ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS) was applied to identify the chemical profiles and absorbed components of ZQD. Network pharmacology was used to identify targets and pathways related to MPS-relieving efficacy. RESULTS The chemicals of ZQDs without/with EP process (referred to as ZQD-W and ZQD-W-P, respectively) were qualitatively similar with 89 and 87 components identified, respectively, but their relative contents were different; 51 components were detectable in the serum of rats orally administered with ZQD-W, whereas only 19 were detected in that administered with ZQD-W-P. Key targets, such as AKT1, and pathways, such as the PI3K-Akt signalling pathway, affected by ZQD-W and ZQD-W-P were similar, while the neuroactive ligand-receptor interaction pathway among others and the MAPK signalling pathway among others were specific pathways affected by ZQD-W and ZQD-W-P, respectively. The specifically absorbed components of ZQD-W could combine its specific key targets. CONCLUSION The EP process quantitatively altered the chemical profiles of ZQD, subsequently affected the absorbed components of ZQD, and then affected the key targets and pathways of ZQD for relieving MPS. The EP process might result in variation of the MPS-relieving efficacy of ZQD, which deserves further in vivo verification.
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Affiliation(s)
- Cheng-Ying Wu
- Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
- Department of Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine and Jiangsu Branch of China Academy of Chinese Medical Sciences, Nanjing, China
| | - Yi-Yin Guo
- Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Zhen-Yue Ma
- Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Jing Zhou
- Department of Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine and Jiangsu Branch of China Academy of Chinese Medical Sciences, Nanjing, China
| | - Fang Long
- Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Hong Shen
- Department of Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine and Jiangsu Branch of China Academy of Chinese Medical Sciences, Nanjing, China
| | - Jin-Di Xu
- Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Shan-Shan Zhou
- Department of Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine and Jiangsu Branch of China Academy of Chinese Medical Sciences, Nanjing, China
| | - Jie-Ge Huo
- Oncology Department, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Can-Hong Hu
- Oncology Department, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Song-Lin Li
- Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
- Department of Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine and Jiangsu Branch of China Academy of Chinese Medical Sciences, Nanjing, China
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Xu Q, Yu Z, Mei Q, Shi K, Shen J, Gao G, Liu S, Li M. Keratin 6A (KRT6A) promotes radioresistance, invasion, and metastasis in lung cancer via p53 signaling pathway. Aging (Albany NY) 2024; 16:7060-7072. [PMID: 38656878 PMCID: PMC11087103 DOI: 10.18632/aging.205742] [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: 12/28/2023] [Accepted: 03/19/2024] [Indexed: 04/26/2024]
Abstract
BACKGROUND It is reported that the incidence rate and mortality of lung cancer are very high. Therefore, early diagnosis and identification of specific biomarkers are crucial for the clinical treatment of lung cancer. This study aims to comprehensively investigate the prognostic significance of KRT6A in human lung cancer. METHODS The GEO2R online tool was utilized to analyze the differential expression of mRNA between lung carcinoma tissues and radioresistant tissues in the GSE73095 and GSE197236 datasets. DAVID database was used to perform GO and KEGG enrichment analyses on target genes. The Kaplan-Meier plotter tool was used to analyze the impact of key messenger ribonucleic acid on the survival status of lung cancer. In addition, quantitative real-time polymerase chain reaction (qPCR) was used to investigate the impact of key genes on the phenotype of lung cancer cells. After the knockout, we conducted cell migration and CCK-8 experiments to detect their effects on cell proliferation and invasion. RESULTS 40 differentially expressed genes (DEGs) were chosen from GSE73095 and 118 DEGs were chosen from GSE197236. Kaplan-Meier map analysis showed that the overall cancer survival rate of the high-expression KRT6A group was higher than that of the low-expression group (P < 0.05). Besides, cell experiments have shown that when the KRT6A gene is downregulated, the proliferation and invasion ability of lung cancer cells is weakened. CONCLUSIONS Our research concluded that KRT6A may take part in the radioresistance and progression of lung cancer and can be a potential biomarker for lung cancer patients.
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Affiliation(s)
- Qiang Xu
- Department of Thoracic Surgery, Suzhou Xiangcheng People’s Hospital, Suzhou, Jiangsu, China
- Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
| | - Ziyang Yu
- Department of Gynaecology and Obstetrics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
| | - Qiteng Mei
- Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
| | - Kejun Shi
- Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
| | - Jiaofeng Shen
- Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
| | - Guangyu Gao
- Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
| | - Songtao Liu
- Department of Ultrasound, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
| | - Ming Li
- Department of Pathology, Suzhou Municipal Hospital affiliated to Nanjing Medical University, Suzhou 215008, People’s Republic of China
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Cheng Z, Fan W, Hu J, Yang D. Two new sesquiterpene glycosides from Dendrobium findleyanum. Nat Prod Res 2024:1-9. [PMID: 38329059 DOI: 10.1080/14786419.2024.2313191] [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: 07/10/2023] [Accepted: 01/29/2024] [Indexed: 02/09/2024]
Abstract
One new ylangene-type sesquiterpene glycoside, findlayanoside C (1), and one new picrotoxane-type sesquiterpene glycoside, findlayanoside D (3), together with five known sesquiterpene glycosides, dendrofindlayanoside C (2), dendronobiloside B (4), dendronobiloside A (5), dendroside F (6) and dendromoniliside D (7), have been isolated from the stems of Dendrobium findleyanum. The structures of compounds 1 and 3 were elucidated by means of extensive spectroscopic analyses, and their absolute configuration were confirmed by electronic circular dichroism (ECD) calculations. Cytotoxic activity assays against SMMC-7721, A-549 and MCF-7 human cancer cell lines revealed IC50 values of 10.12, 12.32 and 14.13 μM for compound 1, and of 9.25, 13.16 and 16.26 μM for compound 2. This study enriches the anti-tumour sesquiterpenoids composition of D. findleyanum.
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Affiliation(s)
- Zhongquan Cheng
- College of Pharmacy, Guangzhou Health Science College, Guangzhou, P. R. China
| | - Weiwei Fan
- Henan Engineering Research Center of Funiu Mountain's Medicinal Resources Utilization and Molecular Medicine, College of Medicine, Pingdingshan University, Pingdingshan, P. R. China
| | - Jiangmiao Hu
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, P. R. China
| | - Dan Yang
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, and School of Pharmacy, Guangdong Medical University, Dongguan, P. R. China
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Fu J, Xie X, Yao H, Xiao H, Li Z, Wang Z, Ju R, Zhao Y, Liu Z, Zhang N. The Effectiveness of Traditional Chinese Medicine in Treating Malignancies via Regulatory Cell Death Pathways and the Tumor Immune Microenvironment: A Review of Recent Advances. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2024; 52:137-160. [PMID: 38328830 DOI: 10.1142/s0192415x2450006x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/09/2024]
Abstract
Traditional Chinese Medicine (TCM) has achieved high clinical efficacy in treating malignancies in recent years and is thus gradually becoming an important therapy for patients with advanced tumor for its benefits in reducing side effects and improving patients' immune status. However, it has not been internationally recognized for cancer treatment because TCM's anti-tumor mechanism is not fully elucidated, limiting its clinical application and international promotion. This review traced the mechanism of the TCM-mediated tumor cell death pathway and its effect on remodeling the tumor immune microenvironment, its direct impact on the microenvironment, its anti-tumor effect in combination with immunotherapy, and the current status of clinical application of TCM on tumor treatment. TCM can induce tumor cell death in many regulatory cell death (RCD) pathways, including apoptosis, autophagy, pyroptosis, necroptosis, and ferroptosis. In addition, TCM-induced cell death could increase the immune cells' infiltration with an anti-tumor effect in the tumor tissue and elevate the proportion of these cells in the spleen or peripheral blood, enhancing the anti-tumor capacity of the tumor-bearing host. Moreover, TCM can directly affect immune function by increasing the population or activating the sub-type immune cells with an anti-tumor role. It was concluded that TCM could induce a pan-tumor death modality, remodeling the local TIME differently. It can also improve the systemic immune status of tumor-bearing hosts. This review aims to establish a theoretical basis for the clinical application of TCM in tumor treatment and to provide a reference for TCM's potential in combination with immunotherapy in cancer treatment.
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Affiliation(s)
- Jingya Fu
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710049, P. R. China
- Shaanxi University of Chinese Medicine Xian yang 712046, P. R. China
- The First Affiliated Hospital of Nanyang Medical College Nanyang 473000, P. R. China
| | - Xiaoxia Xie
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710049, P. R. China
- Shaanxi University of Chinese Medicine Xian yang 712046, P. R. China
| | - Huimin Yao
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710049, P. R. China
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061, P. R. China
- Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061, P. R. China
| | - Haijuan Xiao
- Shaanxi University of Chinese Medicine Xian yang 712046, P. R. China
| | - Zhuoqun Li
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061, P. R. China
- Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061, P. R. China
| | - Zhenzhi Wang
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710049, P. R. China
- Shaanxi University of Chinese Medicine Xian yang 712046, P. R. China
| | - Ran Ju
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710049, P. R. China
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061, P. R. China
- Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061, P. R. China
| | - Yan Zhao
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710049, P. R. China
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061, P. R. China
- Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061, P. R. China
| | - Zhijun Liu
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710049, P. R. China
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061, P. R. China
- Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061, P. R. China
| | - Nana Zhang
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710049, P. R. China
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061, P. R. China
- Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061, P. R. China
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Li M, Zhao Y, Li H, Kang S, Deng X, Sheng M. Mechanism of Erianin anti-triple negative breast cancer based on transcriptomics methods and network pharmacology. Aging (Albany NY) 2024; 16:2848-2865. [PMID: 38329441 PMCID: PMC10911376 DOI: 10.18632/aging.205516] [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: 09/04/2023] [Accepted: 12/13/2023] [Indexed: 02/09/2024]
Abstract
Triple negative breast cancer (TNBC) is a highly aggressive illness that lacks effective targeted treatments. Although Erianin has shown potential antitumor properties, its precise mechanism of action and target in TNBC remain unclear, hampering the development of drugs. The present study investigated the underlying mechanism of action of Erianin in treating TNBC by using transcriptomics and network pharmacology approaches. We evaluated Erianin's bioactivity in TNBC cell lines and xenograft tumor models. The results showed that Erianin significantly inhibited TNBC cell proliferation and impeded tumor growth. A subsequent analysis of transcriptomic and network pharmacological data identified 51 mutual targets. Analysis of protein-protein interactions identified eight hub targets. Furthermore, molecular docking indicated that the PPARA binding energy was the lowest for Erianin among the hub targets, followed by ROCK2, PDGFRB, CCND1, MUC1, and CDK1. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis showed that the common targets were associated with multiple cancer-related signaling pathways, including focal adhesion, PI3K-Akt signaling pathway, Rap1 signaling pathway, microRNAs in cancer, and human papillomavirus infection. The results of the Western blot and immunohistochemistry experiment further showed that Erianin could suppress PI3K/Akt signaling pathway activation. After co-incubation with SC79, the cell inhibition rate of Erianin was decreased, which further confirmed that Erianin inhibits TNBC progression via the PI3K-AKT signaling pathway. In conclusion, our results indicated that Erianin has the potential to inhibit the proliferation of TNBC by downregulating the PI3K/AKT signaling pathway by transcriptomics and network pharmacology. Therefore, Erianin appears to be a promising compound for the effective treatment of TNBC.
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Affiliation(s)
- Ming Li
- Laboratory of Molecular Genetics of Aging and Tumour, Medical School, Kunming University of Science and Technology, Chenggong Campus, Kunming, Yunnan 650500, China
| | - Yuan Zhao
- Kunming University of Science and Technology Affiliated Puer City People’s Hospital, Puer, Yunnan 665000, China
| | - Huimin Li
- Laboratory of Molecular Genetics of Aging and Tumour, Medical School, Kunming University of Science and Technology, Chenggong Campus, Kunming, Yunnan 650500, China
| | - Shiyao Kang
- Laboratory of Molecular Genetics of Aging and Tumour, Medical School, Kunming University of Science and Technology, Chenggong Campus, Kunming, Yunnan 650500, China
| | - Xuming Deng
- Laboratory of Molecular Genetics of Aging and Tumour, Medical School, Kunming University of Science and Technology, Chenggong Campus, Kunming, Yunnan 650500, China
| | - Miaomiao Sheng
- Laboratory of Molecular Genetics of Aging and Tumour, Medical School, Kunming University of Science and Technology, Chenggong Campus, Kunming, Yunnan 650500, China
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Weng J, Wu XF, Shao P, Liu XP, Wang CX. Medicine for chronic atrophic gastritis: a systematic review, meta- and network pharmacology analysis. Ann Med 2024; 55:2299352. [PMID: 38170849 PMCID: PMC10769149 DOI: 10.1080/07853890.2023.2299352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 12/21/2023] [Indexed: 01/05/2024] Open
Abstract
PURPOSE The aim of this study is to determine the effectiveness and reliability of adding traditional Chinese medicine (TCM) in the clinical intervention and explore mechanisms of action for chronic atrophic gastritis (CAG) through meta- and network pharmacology analysis (NPAs). METHODS A predefined search strategy was used to retrieve literature from PubMed, Embase database, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Database (CBM), Wan Fang Data and China Science and Technology Journal Database (VIP). After applying inclusion and exclusion criteria, a total of 12 randomized controlled trials (RCTs) were included for meta-analysis to provide clinical evidence of the intervention effects. A network meta-analysis using Bayesian networks was conducted to observe the relative effects of different intervention measures and possible ranking of effects. The composition of the TCM formulation in the experimental group was analysed, and association rule mining was performed to identify hub herbal medicines. Target genes for CAG were searched in GeneCards, Online Mendelian Inheritance in Man, PharmGKB, Therapeutic Target Database and DrugBank. A regulatory network was constructed to connect the target genes with active ingredients of the hub herbal medicines. Enrichment analyses were performed using the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to examine the central targets from a comprehensive viewpoint. Protein-protein interaction networks (PPINs) were constructed to identify hub genes and conduct molecular docking with differentially expressed genes (DEGs) and corresponding active molecules. RESULTS A total of 1140 participants from 12 RCTs were included in the statistical analysis, confirming that the experimental group receiving the addition of TCM intervention had better clinical efficacy. Seven hub TCMs (Paeonia lactiflora, Atractylodes macrocephala, Pinellia ternata, Citrus reticulata, Codonopsis pilosula, Salvia miltiorrhiza and Coptis chinensis) were identified through association rule analysis of all included TCMs. Thirteen hub genes (CDKN1A, CASP3, STAT1, TP53, JUN, MAPK1, STAT3, MAPK3, MYC, HIF1A, FOS, MAPK14 and AKT1) were obtained from 90 gene PPINs. Differential gene expression analysis between the disease and normal gastric tissue identified MAPK1 and MAPK3 as the significant genes. Molecular docking analysis revealed that naringenin, luteolin and quercetin were the main active compounds with good binding activities to the two hub targets. GO analysis demonstrated the function of the targets in protein binding, while KEGG analysis indicated their involvement in important pathways related to cancer. CONCLUSIONS The results of a meta-analysis of 12 RCTs indicate that TCM intervention can improve the clinical treatment efficacy of CAG. NPAs identified seven hub TCM and 13 target genes associated with their actions, while bioinformatics analysis identified two DEGs between normal and CAG gastric tissues. Finally, molecular docking was employed to reveal the mechanism of action of the active molecules in TCM on the DEGs. These findings not only reveal the mechanisms of action of the active components of the TCMs, but also provide support for the development of new drugs, ultimately blocking the progression from chronic gastritis to gastric cancer.
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Affiliation(s)
- Jiao Weng
- Liaoning University of Traditional Chinese Medicine, Shenyang, China
| | - Xiu-fang Wu
- The Second Hospital Affiliated with Shenyang Medical University, Shenyang, China
| | - Peng Shao
- The Second Hospital Affiliated with Shenyang Medical University, Shenyang, China
| | - Xing-pu Liu
- The Second Hospital Affiliated with Shenyang Medical University, Shenyang, China
| | - Cai-xia Wang
- Liaoning University of Traditional Chinese Medicine, Shenyang, China
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Wang C, Zhang R, Chen X, Yuan M, Wu J, Sun Q, Miao C, Jing Y. The potential effect and mechanism of Saikosaponin A against gastric cancer. BMC Complement Med Ther 2023; 23:295. [PMID: 37608281 PMCID: PMC10463516 DOI: 10.1186/s12906-023-04108-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Accepted: 07/28/2023] [Indexed: 08/24/2023] Open
Abstract
BACKGROUND Saikosaponin A (SSA) shows a series of pharmacological activities, such as anti-inflammatory, antioxidant and antitumor. However, there is a lack of comprehensive research or sufficient evidence regarding the efficacy of SSA in treating gastric cancer (GC), and the specific mechanisms by which it inhibits GC growth and progression are still not fully understood. METHODS MTT and clonogenic assays were employed to detect the effect of SSA on the proliferation of GC cells. Bioinformatics predicted the SSA targets in the treatment of GC. The core genes and the underlying mechanism of SSA in anti-GC were obtained by analyzing the intersecting targets; molecular docking and Western blot were used to check the reliability of core genes. Flow cytometry was used to analyze apoptosis and cell cycle in GC cells treated with varying concentrations of SSA. Western blot was employed to detect the expression levels of related proteins. RESULTS SSA significantly blocked GC cells in the S phase of the cell cycle and induced apoptosis to suppress the proliferation of GC cells. Network pharmacology revealed that the underlying mechanisms through which SSA acts against GC involve the modulation of several signaling pathways, including the PI3K-Akt, MAPK, RAS, and T-cell signaling pathways. Molecular docking showed pivotal target genes with a high affinity to SSA, including STAT3, MYC, TNF, STAT5B, Caspase-3 and SRC. Furthermore, western blot results revealed that SSA significantly increased the protein levels of Bax and Cleaved Caspase-3, whereas decreased the expression levels of p-JAK, p-STAT3, MYC, Bcl-2, p-PI3K, p-AKT and p-mTOR, confirming that the reliability of hub targets and SSA could promote GC cell apoptosis by suppressing PI3K/AKT/mTOR pathway. CONCLUSIONS The results suggest that SSA has the ability to trigger apoptosis in GC cells by blocking the PI3K/AKT/mTOR pathway. These findings highlight the potential of SSA as a promising natural therapeutic agent for the treatment of GC.
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Affiliation(s)
- Chao Wang
- China Pharmaceutical University, Nanjing Drum Tower Hospital, Nanjing, 210008, Jiangsu Province, China
| | - Ruijuan Zhang
- Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China
| | - Xu Chen
- Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China
| | - Mengyun Yuan
- Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China
| | - Jian Wu
- Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, Jiangsu, China
| | - Qingmin Sun
- Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, Jiangsu, China
| | - Chunrun Miao
- Department of Gastroenterology, Dongtai Hospital of Traditional Chinese Medicine, Dongtai, 224299, Jiangsu, China.
| | - Yali Jing
- China Pharmaceutical University, Nanjing Drum Tower Hospital, Nanjing, 210008, Jiangsu Province, China.
- Department of Endocrinology, Drum Tower Hospital Affiliated to Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, 210008, Jiangsu, China.
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Lu L, Chen B, Zhang X, Xu Y, Jin L, Qian H, Liang ZF. The effect of phytochemicals in N-methyl-N-nitro-N-nitroguanidine promoting the occurrence and development of gastric cancer. Front Pharmacol 2023; 14:1203265. [PMID: 37456745 PMCID: PMC10339287 DOI: 10.3389/fphar.2023.1203265] [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: 04/10/2023] [Accepted: 06/20/2023] [Indexed: 07/18/2023] Open
Abstract
Gastric cancer is a common malignant tumor of the digestive tract, with a low early diagnosis rate. N-methyl-N-nitro-N-nitroguanidine (MNNG) is one of the main risk factors for gastric cancer. Phytochemicals are healthy active substances derived from vegetables, fruits, nuts, tea, herbal medicines and other plants. Taking phytochemicals is a very promising strategy for the prevention and treatment of gastric cancer. Many studies have proved that phytochemicals have protective effects on MNNG induced gastric cancer via inhibiting cell proliferation, enhancing immunity, suppressing cell invasion and migration, inducing apoptosis and autophagy, blocking angiogenesis, inhibiting Helicobacter pylori infection as well as regulating metabolism and microbiota. The intervention and therapeutic effects of phytochemicals in MNNG induced gastric cancer have attracted more and more attention. In order to better study and explore the role, advantages and challenges of phytochemicals in MNNG induced gastric cancer, we summarized the intervention and therapeutic effects of phytochemicals in MNNG induced gastric cancer. This review may help to further promote the research and clinical application of phytochemicals in MNNG induced gastric cancer, and provide some new insights.
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Affiliation(s)
- Ling Lu
- Child Healthcare Department, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Bei Chen
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
| | - XinYi Zhang
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Yumeng Xu
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Longtao Jin
- Child Healthcare Department, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Hui Qian
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Zhao feng Liang
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
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Zhang H, Zhuo H, Hou J, Cai J. Machine learning models predict the mTOR signal pathway-related signature in the gastric cancer involving 2063 samples of 7 centers. Aging (Albany NY) 2023; 15:6152-6162. [PMID: 37341987 PMCID: PMC10373976 DOI: 10.18632/aging.204817] [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: 03/14/2023] [Accepted: 05/17/2023] [Indexed: 06/22/2023]
Abstract
Gastric cancer, as a tumor with poor prognosis, has been widely studied. Distinguishing the types of gastric cancer is helpful. Using the transcriptome data of gastric cancer in our study, relevant proteins of mTOR signaling pathway were screened to identify key genes by four machine learning models, and the models were validated in external datasets. Through correlation analysis, we explored the relationship between five key genes and immune cells and immunotherapy. By inducing cellular senescence in gastric cancer cells with bleomycin, we investigated changes in the expression levels of HRAS through western blot. By PCA clustering analysis, we used the five key genes for gastric cancer typing and explored differences in drug sensitivity and enrichment pathways between different clustering groups. We found that the SVM machine learning model was superior, and the five genes (PPARA, FNIP1, WNT5A, HRAS, HIF1A) were highly correlated with different immune cells in multiple databases. These five key genes have a significant impact on immunotherapy. Using the five genes for gastric cancer gene typing, four genes were expressed higher in group 1 and were more sensitive to drugs in group 2. These results suggest that subtype-specific markers can improve the treatment and provide precision drugs for gastric cancer patients.
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Affiliation(s)
- Hao Zhang
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, Fujian, China
- Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen 361004, Fujian, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen 361004, Fujian, China
| | - Huiqin Zhuo
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, Fujian, China
- Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen 361004, Fujian, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen 361004, Fujian, China
| | - Jingjing Hou
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, Fujian, China
- Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen 361004, Fujian, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen 361004, Fujian, China
| | - Jianchun Cai
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, Fujian, China
- Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen 361004, Fujian, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen 361004, Fujian, China
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Qin H, Zhang S, Shen L, Mao C, Gao G, Wang H. High expression of serine protease 2 (PRSS2) associated with invasion, metastasis, and proliferation in gastric cancer. Aging (Albany NY) 2023; 15:2473-2484. [PMID: 37022096 PMCID: PMC10120911 DOI: 10.18632/aging.204604] [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: 11/23/2022] [Accepted: 03/08/2023] [Indexed: 04/07/2023]
Abstract
BACKGROUND Accumulating evidence indicates that the occurrence and development of tumors are related to the activation of oncogenes and the inactivation of tumor suppressor genes caused by epigenetic mechanisms. However, the function of serine protease 2 (PRSS2) in gastric cancer (GC) is still unknown. Our study aimed to find a regulation network involved in GC. METHODS The mRNA data (GSE158662 and GSE194261) of GC and normal tissues were downloaded from the Gene Expression Omnibus (GEO) dataset. Differential expression analysis was performed using R software, and Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted by using Xiantao software. Besides, we used Quantitative Real-time PCR (qPCR) to verify our conclusions. After gene knockdown, cell migration and CCK-8 experiment were carried out to detect the effect of gene on cell proliferation and invasion. RESULTS Totally, 412 differentially expressed genes (DEGs) were identified from GSE158662 and 94 DEGs were identified from GSE196261. Km-plot database results indicated that PRSS2 exhibited high diagnosis worth for GC. Gene functional annotation enrichment analysis revealed that these hub mRNAs were mainly taken part in the process of tumorigenesis and development. Besides, vitro experiments showed that down-regulation of PRSS2 gene reduced the proliferation and invasion ability of GC cells. CONCLUSIONS Our results indicated that PRSS2 may play vital roles in the carcinogenesis and progression of GC and can be potential biomarkers for patients with GC.
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Affiliation(s)
- Haifeng Qin
- Department of Nuclear Medicine, First People’s Hospital of Kunshan, Kunshan, Suzhou 215004, Jiangsu Province, China
- Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu Province, China
| | - Shushu Zhang
- Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu Province, China
| | - Linling Shen
- Department of Ultrasound, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu Province, China
| | - Chenjian Mao
- Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu Province, China
| | - Guangyu Gao
- Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu Province, China
| | - Hui Wang
- Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu Province, China
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Zhang Z, He C, Bao C, Li Z, Jin W, Li C, Chen Y. MiRNA Profiling and Its Potential Roles in Rapid Growth of Velvet Antler in Gansu Red Deer ( Cervus elaphus kansuensis). Genes (Basel) 2023; 14:424. [PMID: 36833351 PMCID: PMC9957509 DOI: 10.3390/genes14020424] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 01/31/2023] [Accepted: 02/02/2023] [Indexed: 02/11/2023] Open
Abstract
A significant variety of cell growth factors are involved in the regulation of antler growth, and the fast proliferation and differentiation of various tissue cells occur during the yearly regeneration of deer antlers. The unique development process of velvet antlers has potential application value in many fields of biomedical research. Among them, the nature of cartilage tissue and the rapid growth and development process make deer antler a model for studying cartilage tissue development or rapid repair of damage. However, the molecular mechanisms underlying the rapid growth of antlers are still not well studied. MicroRNAs are ubiquitous in animals and have a wide range of biological functions. In this study, we used high-throughput sequencing technology to analyze the miRNA expression patterns of antler growth centers at three distinct growth phases, 30, 60, and 90 days following the abscission of the antler base, in order to determine the regulatory function of miRNA on the rapid growth of antlers. Then, we identified the miRNAs that were differentially expressed at various growth stages and annotated the functions of their target genes. The results showed that 4319, 4640, and 4520 miRNAs were found in antler growth centers during the three growth periods. To further identify the essential miRNAs that could regulate fast antler development, five differentially expressed miRNAs (DEMs) were screened, and the functions of their target genes were annotated. The results of KEGG pathway annotation revealed that the target genes of the five DEMs were significantly annotated to the "Wnt signaling pathway", "PI3K-Akt signaling pathway", "MAPK signaling pathway", and "TGF-β signaling pathway", which were associated with the rapid growth of velvet antlers. Therefore, the five chosen miRNAs, particularly ppy-miR-1, mmu-miR-200b-3p, and novel miR-94, may play crucial roles in rapid antler growth in summer.
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Affiliation(s)
- Zhenxiang Zhang
- Qinghai Provincial Key Laboratory of Adaptive Management on Alpine Grassland, Academy of Animal Science and Veterinary Medicine, Qinghai University, Xining 810016, China
- College of Eco–Environmental Engineering, Qinghai University, Xining 810016, China
| | - Caixia He
- College of Eco–Environmental Engineering, Qinghai University, Xining 810016, China
| | - Changhong Bao
- College of Eco–Environmental Engineering, Qinghai University, Xining 810016, China
| | - Zhaonan Li
- College of Eco–Environmental Engineering, Qinghai University, Xining 810016, China
| | - Wenjie Jin
- College of Eco–Environmental Engineering, Qinghai University, Xining 810016, China
| | - Changzhong Li
- College of Eco–Environmental Engineering, Qinghai University, Xining 810016, China
| | - Yanxia Chen
- College of Eco–Environmental Engineering, Qinghai University, Xining 810016, China
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Zhu Y, Luo L, Zhang M, Song X, Wang P, Zhang H, Zhang J, Liu D. Xuanfei Baidu Formula attenuates LPS-induced acute lung injury by inhibiting the NF-κB signaling pathway. JOURNAL OF ETHNOPHARMACOLOGY 2023; 301:115833. [PMID: 36252879 PMCID: PMC9562620 DOI: 10.1016/j.jep.2022.115833] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 09/29/2022] [Accepted: 10/09/2022] [Indexed: 05/26/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Acute lung injury (ALI) is a common manifestation of COVID-19. Xuanfei Baidu Formula(XFBD) is used in China to treat mild or common damp-toxin obstructive pulmonary syndrome in COVID-19 patients. However, the active ingredients of XFBD have not been extensively studied, and its mechanism of action in the treatment of ALI is not well understood. AIM OF THE STUDY The purpose of this study was to investigate the mechanism of action of XFBD in treating ALI in rats, by evaluating its active components. MATERIALS AND METHODS Firstly, the chemical composition of XFBD was identified using ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry. The potential targets of XFBD for ALI treatment were predicted using network pharmacological analysis. Finally, the molecular mechanism of XFBD was validated using a RAW264.7 cell inflammation model and a mouse ALI model. RESULTS A total of 113 compounds were identified in XFBD. Network pharmacology revealed 34 hub targets between the 113 compounds and ALI. The results of Kyoto Encyclopedia of Genes and Genomes and gene ontology analyses indicated that the NF-κB signaling pathway was the main pathway for XFBD in the treatment of ALI. We found that XFBD reduced proinflammatory factor levels in LPS-induced cellular models. By examining the lung wet/dry weight ratio and pathological sections in vivo, XFBD was found that XFBD could alleviate ALI. Immunohistochemistry results showed that XFBD inhibited ALI-induced increases in p-IKK, p-NF-κB p65, and iNOS proteins. In vitro experiments demonstrated that XFBD inhibited LPS-induced activation of the NF-κB pathway. CONCLUSION This study identified the potential practical components of XFBD, combined with network pharmacology and experimental validation to demonstrate that XFBD can alleviate lung injury caused by ALI by inhibiting the NF-κB signaling pathway.
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Affiliation(s)
- Yanru Zhu
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Tianjin Modern Innovation Chinese Medicine Technology Co., Ltd., Tianjin, China
| | - Lifei Luo
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Tianjin Modern Innovation Chinese Medicine Technology Co., Ltd., Tianjin, China
| | - Meng Zhang
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Tianjin Modern Innovation Chinese Medicine Technology Co., Ltd., Tianjin, China
| | - Xinbo Song
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Tianjin Modern Innovation Chinese Medicine Technology Co., Ltd., Tianjin, China
| | - Ping Wang
- Tianjin Modern Innovation Chinese Medicine Technology Co., Ltd., Tianjin, China
| | - Han Zhang
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Jingze Zhang
- Tianjin Modern Innovation Chinese Medicine Technology Co., Ltd., Tianjin, China
| | - Dailin Liu
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Tianjin Modern Innovation Chinese Medicine Technology Co., Ltd., Tianjin, China.
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Zhong YL, Wang PQ, Hao DL, Sui F, Zhang FB, Li B. Traditional Chinese medicine for transformation of gastric precancerous lesions to gastric cancer: A critical review. World J Gastrointest Oncol 2023; 15:36-54. [PMID: 36684050 PMCID: PMC9850768 DOI: 10.4251/wjgo.v15.i1.36] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 12/06/2022] [Accepted: 12/28/2022] [Indexed: 01/10/2023] Open
Abstract
Gastric cancer (GC) is a common gastrointestinal tumor. Gastric precancerous lesions (GPL) are the last pathological stage before normal gastric mucosa transforms into GC. However, preventing the transformation from GPL to GC remains a challenge. Traditional Chinese medicine (TCM) has been used to treat gastric disease for millennia. A series of TCM formulas and active compounds have shown therapeutic effects in both GC and GPL. This article reviews recent progress on the herbal drugs and pharmacological mechanisms of TCM in preventing the transformation from GPL to GC, especially focusing on anti-inflammatory, anti-angiogenesis, proliferation, and apoptosis. This review may provide a meaningful reference for the prevention of the transformation from GPL to GC using TCM.
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Affiliation(s)
- Yi-Lin Zhong
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Peng-Qian Wang
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Dan-Li Hao
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Feng Sui
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Feng-Bin Zhang
- Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
| | - Bing Li
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
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Yang Z, Liu R, Qiu M, Mei H, Hao J, Song T, Zhao K, Zou D, Wang H, Gao M. The roles of ERIANIN in tumor and innate immunity and its' perspectives in immunotherapy. Front Immunol 2023; 14:1170754. [PMID: 37187758 PMCID: PMC10175588 DOI: 10.3389/fimmu.2023.1170754] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 04/18/2023] [Indexed: 05/17/2023] Open
Abstract
Traditional Chinese medicine has been used in China for thousands of years. In 2022, the 14th Five-Year Plan for the Development of Traditional Chinese Medicine was released, aiming to enhance traditional Chinese medicine health services and improve policies and systems for high-quality traditional Chinese medicinal development by 2025. ERIANIN, the main component of the traditional Chinese medicine Dendrobium, plays an important role in anti-inflammatory, antiviral, antitumor, antiangiogenic, and other pharmacological effects. ERIANIN has broad-spectrum antitumor effects, and its tumor-suppressive effects have been confirmed in the study of various diseases, such as precancerous lesions of the stomach, gastric cancer, liver cancer, lung cancer, prostate cancer, bladder cancer, breast cancer, cervical cancer, osteosarcoma, colorectal cancer, leukaemia, nasopharyngeal cancer and melanoma through the multiple signaling pathways. Thus, the aim of this review was to systematically summarise the research on ERIANIN with the aim of serving as a reference for future research on this compound and briefly discuss some future perspectives development of ERIANIN in combined immunotherapy.
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Affiliation(s)
- Zhen Yang
- Department of Oncology, Tianjin Union Medical Center of Nankai University, Tianjin, China
- The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, China
| | - Ruxue Liu
- College of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Minghan Qiu
- Department of Oncology, Tianjin Union Medical Center of Nankai University, Tianjin, China
- The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, China
| | - Hanwei Mei
- College of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Jie Hao
- Department of Thyroid and Breast Surgery, Tianjin Key Laboratory of General Surgery in Construction, Tianjin Union Medical Center, Tianjin, China
| | - Teng Song
- Department of Oncology, Tianjin Union Medical Center of Nankai University, Tianjin, China
- The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, China
| | - Ke Zhao
- Department of Oncology, Tianjin Union Medical Center of Nankai University, Tianjin, China
- The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, China
| | - Dandan Zou
- Department of Oncology, Tianjin Union Medical Center of Nankai University, Tianjin, China
- The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, China
| | - Huaqing Wang
- Department of Oncology, Tianjin Union Medical Center of Nankai University, Tianjin, China
- The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, China
- College of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- *Correspondence: Huaqing Wang, ; Ming Gao,
| | - Ming Gao
- Department of Thyroid and Breast Surgery, Tianjin Key Laboratory of General Surgery in Construction, Tianjin Union Medical Center, Tianjin, China
- *Correspondence: Huaqing Wang, ; Ming Gao,
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Wang C, Chen H, Song S, Chen B, Li R, Fu Z, Zhang Z, Wang Q, Han L. Discovery of metabolic markers for the discrimination of Helwingia species based on bioactivity evaluation, plant metabolomics, and network pharmacology. RAPID COMMUNICATIONS IN MASS SPECTROMETRY : RCM 2022; 36:e9411. [PMID: 36195983 DOI: 10.1002/rcm.9411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 10/01/2022] [Accepted: 10/02/2022] [Indexed: 06/16/2023]
Abstract
RATIONALE Helwingia japonica (HJ), a traditional medicinal plant, is commonly used for the treatment of dysentery, blood in the stool, and scald burns. Three major HJ species, Helwingia japonica (Thunb.) Dietr. (QJY), Helwingia himalaica Hook. f. et Thoms. ex C. B. Clarke, and Helwingia chinensis Batal., share great similarities in both morphology and chemical constituents. The discrimination of medicinal plants directly affects their pharmacological and clinical effects. Here, we solved the taxonomy uncertainty of these three HJ species and explored the discrimination and study of other traditional medicines (TMs). METHODS First, the anti-inflammatory effects of the three HJ species were compared using lipopolysaccharide (LPS)-induced inflammatory responses in mouse leukemia cells of monocyte macrophage (RAW) 264.7 cells. Then, plant metabolomics were performed in 48 batches of samples to discover chemical markers for discriminating different HJ species. Finally, network pharmacology was applied to explore the linkages among constituents, targets, and signaling pathways. RESULTS In vitro experiments showed that the QJY exhibited the most potential anti-inflammatory activities. Meanwhile, 172 compounds were tentatively identified and eight metabolites with higher relative content in QJY were designated as chemical markers to distinguish QJY and the other two species. According to the property of absorbed in vivo, threonic acid, arginine, and tyrosine were selected to construct a component-target-pathway network. The network pharmacology analysis confirmed that the chemotaxonomy differentiation was consistent with the bioactive assessment. CONCLUSIONS The present study demonstrates that bioactivity evaluation integrated with plant metabolomics and network pharmacology could be used as an effective approach to discriminate different TMs and discover the active compounds.
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Affiliation(s)
- Chenxi Wang
- State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, P. R. China
| | - Hao Chen
- State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, P. R. China
| | - Shaofei Song
- State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, P. R. China
| | - Biying Chen
- State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, P. R. China
| | - Rongrong Li
- State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, P. R. China
| | - Zhifei Fu
- State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, P. R. China
| | - Zhonglian Zhang
- Yunnan Key Laboratory of Southern Medicine Utilization, Yunnan Branch of Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Jinghong, China
| | - Qilong Wang
- State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, P. R. China
| | - Lifeng Han
- State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, P. R. China
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Chu YM, Wang TX, Jia XF, Yang Y, Shi ZM, Cui GH, Huang QY, Ye H, Zhang XZ. Fuzheng Nizeng Decoction regulated ferroptosis and endoplasmic reticulum stress in the treatment of gastric precancerous lesions: A mechanistic study based on metabolomics coupled with transcriptomics. Front Pharmacol 2022; 13:1066244. [PMID: 36506541 PMCID: PMC9727497 DOI: 10.3389/fphar.2022.1066244] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Accepted: 11/07/2022] [Indexed: 11/24/2022] Open
Abstract
Background: Fuzheng Nizeng Decoction (FZNZ) has a history of decades in gastric precancerous lesions (GPL) treatment, which has shown clear clinical efficacy. Blocking GPL is a key measure to reduce the incidence of gastric cancer (GC). Therefore, we aim to investigate the mechanism of FZNZ-induced ferroptosis and endoplasmic reticulum (ER) in MNNG-induced gastric precancerous lesion (MC) cells, which has been rarely studied in Traditional Chinese Medicine (TCM). Methods: First, CCK8 and lactate dehydrogenase assays were conducted to study the potential effect of FZNZ on MC cells. Second, combined transcriptomic and metabolomic analysis were used to explore the effect and mechanism of FZNZ. Functionally, the occurrence of ferroptosis was assessed by transmission electron microscopy morphological observation and measurement of ferrous iron levels, lipid peroxidation, and glutathione levels. Finally, the expression levels of mRNAs or proteins related to ferroptosis and ER stress were determined by qPCR or western blot assays, respectively. Results: FZNZ inhibited MC cells viability and induced cell death. By metabolomics coupled with transcriptomics analysis, we found that the mechanism of FZNZ treatment induced ferroptosis and was related to glutathione metabolism and ER stress. We then, for the first time, found that FZNZ induced ferroptosis, which contributed to an increase in intracellular ferrous iron, reactive oxygen species, and malondialdehyde and a decrease in glutathione. Meanwhile, the protein level of glutathione peroxidase 4 (GPX4) was decreased. The mRNA levels of ATF3/CHOP/CHAC1, which are related to ferroptosis and ER stress, were also upregulated. Conclusion: Our results elaborate that FZNZ could induce ferroptosis and ER stress in MC cells, and reduce GPX4/GSH. ATF3/CHOP/CHAC1 may play a crosstalk role, which provides a new molecular mechanism for the treatment of GPL.
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Affiliation(s)
- Ying-Ming Chu
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Institute of Integrated Traditional Chinese and Western Medicine, Peking University, Beijing, China
| | - Ting-Xin Wang
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Xiao-Fen Jia
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Institute of Integrated Traditional Chinese and Western Medicine, Peking University, Beijing, China
| | - Yao Yang
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Institute of Integrated Traditional Chinese and Western Medicine, Peking University, Beijing, China
| | - Zong-Ming Shi
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Institute of Integrated Traditional Chinese and Western Medicine, Peking University, Beijing, China
| | - Guang-Hui Cui
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Institute of Integrated Traditional Chinese and Western Medicine, Peking University, Beijing, China
| | - Qiu-Yue Huang
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Institute of Integrated Traditional Chinese and Western Medicine, Peking University, Beijing, China
| | - Hui Ye
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Institute of Integrated Traditional Chinese and Western Medicine, Peking University, Beijing, China,*Correspondence: Hui Ye, ; Xue-Zhi Zhang,
| | - Xue-Zhi Zhang
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Institute of Integrated Traditional Chinese and Western Medicine, Peking University, Beijing, China,*Correspondence: Hui Ye, ; Xue-Zhi Zhang,
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Identification of Molecular Targets and Underlying Mechanisms of Xiaoji Recipe against Pancreatic Cancer Based on Network Pharmacology. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:4640849. [PMID: 36118824 PMCID: PMC9477627 DOI: 10.1155/2022/4640849] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Accepted: 08/24/2022] [Indexed: 11/17/2022]
Abstract
Traditional Chinese medicine (TCM) is applied in the anticancer adjuvant therapy of various malignancies and pancreatic cancer included. Xiaoji recipe consists several TCM materials with anticancer activities. In our work, we intended to analyze the molecular targets as well as the underlying mechanisms of Xiaoji recipe against pancreatic cancer. A total of 32 active components and 522 potential targets of Xiaoji recipe were selected using the TCMSP and SwissTargetPrediction databases. The potential target gene prediction in pancreatic cancer was performed using OMIM, Disgenet, and Genecards databases, and totally, 998 target genes were obtained. The component-disease network was constructed using the Cytoscape software, and 116 shared targets of pancreatic cancer and Xiaoji recipe were screened out. As shown in the protein–protein interaction (PPI) network, the top 20 hub genes such as TP53, HRAS, AKT1, VEGFA, STAT3, EGFR, and SRC were further selected by degree. GO and KEGG functional enrichment analysis revealed that Xiaoji recipe may affect pancreatic cancer progression by targeting the PI3K/AKT and MAPK signaling pathways. Moreover, we performed in vitro assays to explore the effect of Xiaoji recipe on pancreatic cancer cells. The results revealed that Xiaoji recipe suppressed the viability and migration and promoted the apoptosis of pancreatic cancer cells via the inactivation of PI3K/AKT, MAPK, and STAT3 pathways. The findings of our study suggested the potential of Xiaoji recipe in the targeting therapy of pancreatic cancer.
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A Web-Based Pharmacological Approach to the Mechanism of Action of Rhizoma Phragmitis and Rhizoma Curcumae in the Treatment of Chronic Atrophic Gastritis. CONTRAST MEDIA & MOLECULAR IMAGING 2022; 2022:3483774. [PMID: 36003993 PMCID: PMC9385286 DOI: 10.1155/2022/3483774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/14/2022] [Revised: 06/04/2022] [Accepted: 06/09/2022] [Indexed: 11/18/2022]
Abstract
Objective. To analyze and test the effect of Rhizoma phragmitis and Rhizoma curcumae on the network pharmacology of MAPK (mitogen-activated protein kinase) and TNF (tumor necrosis factor) signaling channels and inflammatory factor target gene regulation in successful modeling of chronic atrophic gastritis rats. Methods. Rats with chronic atrophic gastritis that were modeled successfully were randomly divided into control and study groups and were treated with conventional western medicine or Rhizoma phragmitis and Rhizoma curcumae, respectively. The pharmacological mechanism of action and efficacy were evaluated. Results. The treatment efficiency was 76.32% and 97.37% in the control and study group, respectively. After treatment, the serum tumor necrosis factor-α (TNF-α) and serum malondialdehyde (MDA) levels in the study group were lower than those in the control group and the serum epidermal growth factor (EGF) and superoxide dismutase (SOD) levels in the study group were higher than those in the control group (P < 0.05); the pain behavioral scores in the study group were lower than those in the control group, and the free acid quantity and total acid quantity in the study group were higher than those in the control group (P < 0.05); the serum MTL index in the study group was higher than that in the control group, and the serum gastrin (GAS) and pepsinogen I (PG I) indices in the study group were lower than those in the control group (P < 0.05); the number of 24-hour reflux in the study group was less than that in the control group (P < 0.05), and the longest reflux time in the study group was lower than that in the control group (P < 0.05). Conclusion. Based on the network pharmacological results, Rhizoma phragmitis and Rhizoma curcumae will modulate MAPK, TNF signaling circuits, and inflammatory factor target genes in the chronic atrophic gastritis rat model. This treatment protocol is efficient and beneficial to enhance the gastric function of the chronic atrophic gastritis rat model, while it can alleviate the inflammatory response and significantly reduce the number and duration of reflux, which is a safe and reliable treatment modality.
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Li Y, Li T, Chen J, Zheng H, Li Y, Chu F, Wang S, Li P, Lin J, Su Z, Ding X. Manpixiao Decoction Halted the Malignant Transformation of Precancerous Lesions of Gastric Cancer: From Network Prediction to In-Vivo Verification. Front Pharmacol 2022; 13:927731. [PMID: 35991884 PMCID: PMC9389883 DOI: 10.3389/fphar.2022.927731] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Accepted: 06/13/2022] [Indexed: 11/29/2022] Open
Abstract
Manpixiao decoction (MPX), a traditional Chinese medicine formula, is mainly used to improve the gastric mucosal pathology and stomach discomfort in patients with gastric precancerous lesions. Precancerous lesion of gastric cancer (PLGC) refers to intestinal metaplasia and/or dysplasia based on gastric mucosal atrophy. Effective prevention and treatment of PLGC is of great significance to reduce the incidence of gastric cancer. Because of the complexity of the etiology and pathogenesis of PLGC, there is no unified and effective treatment plan in western medicine. In recent years, traditional Chinese medicine has shown obvious advantages in the treatment of PLGC and the prevention of its further progression to gastric cancer, relying on its multi-approach and multi-target comprehensive intervention characteristics. This study is designed to examine the protective effect of MPX against PLGC and further to reveal the engaged mechanism via integrating network pharmacology and in vivo experimental evidence. Network pharmacology results demonstrated that inflammation, immune responses, and angiogenesis might be associated with the efficacy of MPX in the treatment of PLGC, in which the PI3K-Akt, cellular senescence, P53 and protein processing in endoplasmic reticulum were involved. Then, we established a rat model of PLGC using a combination of N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), sodium salicylate, irregular fasting, and ranitidine, and observed the effects after MPX treatment. Our result showed that MPX improved the pathological condition of gastric mucosa in PLGC rats and reduced the incidence of gastric cancer. Next, the analysis of serum inflammatory cytokines showed that MPX reduced the inflammation-related cytokines (such as IL-1α, IL-7, CSF-1, and CSF-3) in the serum. Additionally, MPX also had a regulation effect on the “protein/protein phosphorylation-signaling pathway” network in the core region of the PLGC rats. It is showed that MPX can inhibit the phosphorylation of PI3K-AKT, and downregulates the EGFR, β-catenin, and N-cadherin protein levels. These results indicate that MPX halted the PLGC progression through inhibiting EGFR-PI3K-AKT related epithelial-mesenchymal transition process.
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Affiliation(s)
- Yuan Li
- National Institute of Traditional Chinese Medicine Constitution and Preventive Treatment of Diseases, Beijing University of Chinese Medicine, Beijing, China
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
- Research Center for Spleen and Stomach Diseases of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Tao Li
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Jiena Chen
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Haocheng Zheng
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Yicong Li
- Oncology Department, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Fuhao Chu
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
- Research Center for Spleen and Stomach Diseases of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
- Institute of Regulatory Science for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Sici Wang
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Ping Li
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Jie Lin
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Zeqi Su
- Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Xia Ding
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
- Research Center for Spleen and Stomach Diseases of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
- *Correspondence: Xia Ding,
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Cai Y, Cao Y, Cheng S, Zou L, Yang T, Zhang Y, Shou Q, Chen B, Chen W. Study on the Mechanism of Sancao Tiaowei Decoction in the Treatment of MNNG-Induced Precancerous Lesions of Gastric Carcinoma Through Hedgehog Signaling Pathway. Front Oncol 2022; 12:841553. [PMID: 35646631 PMCID: PMC9132047 DOI: 10.3389/fonc.2022.841553] [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: 12/22/2021] [Accepted: 04/06/2022] [Indexed: 11/15/2022] Open
Abstract
Sancao Tiaowei Decoction (SCTWD), a traditional Chinese medicine created by Professor Chen Weijian, has been used in the prevention and treatment of precancerous lesions of gastric carcinoma (PLGC). However, its mechanism has not been made clear. This study aimed to evaluate the therapeutic effect of SCTWD on 1-methyl-3-nitro-1-nitrosoguanidine-induced PLGC in rats and the mechanism of this effect. We found that SCTWD effectively repaired gastric mucosal injury, reversed the process of PLGC, and inhibited the occurrence of gastric cancer to some extent. In the results of hematoxylin-eosin (HE) staining, the number and arrangement of mucosal glands and the number of mononuclear cells in the lamina propria were improved in varying degrees; the enzyme-linked immunosorbent assay (ELISA) showed that the PG I and PGR of the medication treatment group were significantly higher; a Reverse Transcription-Polymerase Chain Reaction (RT-PCR) test showed that SCTWD could significantly upregulate the expression levels of Shh, Ptch, and Gli-1 in the gastric tissue of rats. The immunohistochemical method showed that SCTWD could significantly upregulate the protein expressions of Shh, Gli-1, Smo, cyclin D1, CDKN2A/p16INK4a, and NF-κBP65 and could reduce the expression of Ptch at the same time. Through the preliminary analysis of 75 compounds screened by UPLC-Q-TOF-MS, the main components, such as organic acids, esters and anhydrides, flavonoids, phenols, tanshinones, and so on, have anti-inflammatory and anti-tumor pharmacological effects. The results of KEGG enrichment analysis showed that 5 signaling pathways related to this project were found, and 33 differential genes were presented to construct the interaction network. These results suggested that SCTWD had a good regulatory effect on PLGC and thus may have a multi-targeted effect; SCTWD can not only significantly improve the pathological changes of gastric mucosa in rats with PLGC but also exert a strong effect of the regulation of the hedgehog signaling pathway.
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Affiliation(s)
- Yan Cai
- The Second School of Clinical Medical, Zhejiang Chinese Medical University, Hangzhou, China
| | - Ying Cao
- The Second School of Clinical Medical, Zhejiang Chinese Medical University, Hangzhou, China
| | - Shuang Cheng
- Oncology Department, Yuexi County Hospital, Anqing, China
| | - Lijun Zou
- The Second School of Clinical Medical, Zhejiang Chinese Medical University, Hangzhou, China
| | - Ting Yang
- The Second School of Clinical Medical, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yuxin Zhang
- The Second School of Clinical Medical, Zhejiang Chinese Medical University, Hangzhou, China
| | - Qiyang Shou
- The Second School of Clinical Medical, Zhejiang Chinese Medical University, Hangzhou, China.,School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Binhai Chen
- The Second School of Clinical Medical, Zhejiang Chinese Medical University, Hangzhou, China.,Oncology Department, The Second Affiliated Hospital of Zhejiang Chinese Medical University (Xinhua Hospital of Zhejiang Province), Hangzhou, China
| | - Weijian Chen
- The Second School of Clinical Medical, Zhejiang Chinese Medical University, Hangzhou, China.,Oncology Department, The Second Affiliated Hospital of Zhejiang Chinese Medical University (Xinhua Hospital of Zhejiang Province), Hangzhou, China
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Gao J, Yang S, Xie G, Pan J, Zhu F. Integrating Network Pharmacology and Experimental Verification to Explore the Pharmacological Mechanisms of Aloin Against Gastric Cancer. Drug Des Devel Ther 2022; 16:1947-1961. [PMID: 35757520 PMCID: PMC9232097 DOI: 10.2147/dddt.s360790] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Accepted: 05/30/2022] [Indexed: 11/23/2022] Open
Abstract
Purpose This study was designed to evaluate the pharmacological mechanisms of Aloin against gastric cancer (GC) via network pharmacology analysis combined with experimental verification. Methods Using network pharmacology methods, the potential targets of Aloin and targets related to GC were screened from public databases. The protein–protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to predict the core targets and pathways of Aloin against GC. The expressions of major targets predicted by network pharmacology in normal stomach tissues and GC tissues and their relationships with overall survival of GC were searched in GEPIA, HPA and DriverDBv3 database. The results of network pharmacology analysis were verified by in vitro experiments. Results A total of 129 potential targets were retrieved by searching the intersection of Aloin and GC targets. PPI network analysis indicated that 10 targets, including AKT1 and CASP3, were hub genes. GO enrichment analysis involved 93 biological processes, 19 cellular components, and 37 molecular functions. KEGG enrichment analysis indicated that the anti-cancer effect of Aloin was mediated through multiple pathways, such as PI3K-AKT, FoxO and Ras signaling pathway. Among them, the PI3K-AKT signaling pathway, which contained the largest number of enriched genes, may play a greater role in the treatment of GC. The validation of key targets in GEPIA, HPA and DriverDBv3 database showed that the verification results for most core genes were consistent with this study. Then, the results of in vitro experiment indicated that Aloin could inhibit proliferation of NCI-N87 cells and induce cell apoptosis. The results also showed that Aloin could decrease the mRNA and protein expressions of PI3K and AKT, suggesting that Aloin can treat GC by inducing cell apoptosis and regulating the PI3K-AKT signaling pathway. Conclusion This study identified the potential targets of Aloin against GC using network pharmacology and in vitro verification, which provided a new understanding of the pharmacological mechanisms of Aloin in treatment of GC.
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Affiliation(s)
- Jia Gao
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China
| | - Sifu Yang
- Medical Oncology Department, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang, 310014, People’s Republic of China
| | - Guanqun Xie
- College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China
| | - Jieli Pan
- Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China
- Correspondence: Jieli Pan; Feiye Zhu, Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China, Email ;
| | - Feiye Zhu
- Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China
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Ma X, Zhang X, Kong Y, Su B, Wu L, Liu D, Wang X. Therapeutic effects of Panax notoginseng saponins in rheumatoid arthritis: network pharmacology and experimental validation. Bioengineered 2022; 13:14438-14449. [PMID: 36694450 PMCID: PMC9995134 DOI: 10.1080/21655979.2022.2086379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
Panax notoginseng saponins (PNS) have been reported to have good anti-inflammatory effects. However, the anti-inflammatory effect mechanism in rheumatoid arthritis (RA) remains unknown. The focus of this research was to investigate the molecular mechanism of PNS in the treatment of RA. The primary active components of PNS were tested utilizing the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and Analysis Platform based on oral bioavailability and drug-likeness. The target databases for knee osteoarthritis were created using GeneCards and Online Mendelian Inheritance in Man (OMIM). The visual interactive network structure 'active component - action target - illness' was created using Cytoscape software. A protein interaction network was built, and associated protein interactions were analyzed using the STRING database. The key targets were analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) biological process enrichment analyses. The effects of PNS on cell growth were studied in human umbilical vein endothelial cells (HUVECs) treated with various doses of PNS, and the optimum concentration of PNS was identified. PNS was studied for its implication on angiogenesis and migration. The active components of PNS had 114 common targets, including cell metabolism and apoptosis, according to the network analysis. The therapeutic effects of the PNS components were suggested to be mediated through apoptotic and cytokine signaling pathways. In vitro, PNS therapy boosted HUVEC proliferation. Wound healing, Boyden chamber and tube formation tests suggested that PNS may increase HUVEC activity and capillary-like tube branching. This study clarified that for the treatment of RA, PNS has multisystem, multicomponent, and multitargeted properties.
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Affiliation(s)
- Xinnan Ma
- Department of Orthopedic Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Xin Zhang
- Department of Orthopedic Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Yuanhang Kong
- Department of Orthopedic Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Bo Su
- Department of Orthopedic Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Leilei Wu
- Department of Orthopedic Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Daqian Liu
- Department of Orthopedic Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Xintao Wang
- Department of Orthopedic Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
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Huang Y, Yan J, Sun X, Niu Y, Yuan W, Kong L, Qin X, Zi C, Wang X, Sheng J. Anticancer effects of dendrocandin (DDCD) against AKT in HepG2 cells using molecular modeling, DFT, and in vitro study. Struct Chem 2022. [DOI: 10.1007/s11224-022-01944-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Mechanism of Herb Pairs Astragalus mongholicus and Curcuma phaeocaulis Valeton in Treating Gastric Carcinoma: A Network Pharmacology Combines with Differential Analysis and Molecular Docking. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:8361431. [PMID: 35321506 PMCID: PMC8938068 DOI: 10.1155/2022/8361431] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 02/07/2022] [Accepted: 02/11/2022] [Indexed: 02/08/2023]
Abstract
Background Gastric carcinoma (GC) is a kind of digestive tract tumor that is highly malignant and has a very poor prognosis. Although both Astragalus mongholicus (AM, huáng qí) and Curcuma phaeocaulis Valeton (CPV, é zhú) can slow the onset and progression of GC, the mechanism by which AM-CPV works in the treatment of GC is uncertain. Materials and Methods The traditional Chinese medicine network databases TCMSP, TCMID, and ETCM were used to identify the key functional components and associated targets of AM and CPV. To establish a theoretical foundation, the development of gastric cancer (GC) was predicted utilizing a GEO gene chip and TCGA difference analysis mixed with network pharmacology. A herbal-ingredient-target network and a core target-signal pathway network were created using GO and KEGG enrichment analyses. The molecular docking method was used to evaluate seventeen main targets and their compounds. Results Cell activity, reactive oxygen species modification, metabolic regulation, and systemic immune activation may all be involved in the action mechanism of the AM-CPV drug-pair in the treatment of GC. It inhibits the calcium signaling route, the AGE-RAGE signaling system, the cAMP signaling pathway, the PI3K-Akt signaling network, and the MAPK signaling pathway, slowing the progression of GC. The number of inflammatory substances in the tumor microenvironment is reduced, GC cell proliferation is deprived, apoptosis is promoted, and GC progression is retarded through controlling the IL-17 signaling route, TNF signaling pathway, and other inflammation-related pathways. Conclusions The AM-CPV pharmaceutical combination regulates GC treatment via a multitarget, component, and signal pathway with a cooperative and bidirectional regulatory mechanism. Its active constituents may treat GC by regulating the expression of STAT1, MMP9, IL6, HSP90AA1, JUN, CCL2, IFNG, CXCL8, and other targets, as well as activating or inhibiting immune-inflammatory and cancer signaling pathways.
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Yan L, Zhang Z, Liu Y, Ren S, Zhu Z, Wei L, Feng J, Duan T, Sun X, Xie T, Sui X. Anticancer Activity of Erianin: Cancer-Specific Target Prediction Based on Network Pharmacology. Front Mol Biosci 2022; 9:862932. [PMID: 35372513 PMCID: PMC8968680 DOI: 10.3389/fmolb.2022.862932] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Accepted: 02/25/2022] [Indexed: 12/02/2022] Open
Abstract
Erianin is a major bisbenzyl compound extracted from Dendrobium chrysotoxum Lindl., an important traditional Chinese herb. In recent years, a growing body of evidence has proved the potential therapeutic effects of erianin on various cancers, including hepatoma, melanoma, non-small-cell lung carcinoma, myelogenous leukemia, breast cancer, and osteosarcoma. Especially, the pharmacological activities of erianin, such as antioxidant and anticancer activity, have been frequently demonstrated by plenty of studies. In this study, we firstly conducted a systematic review on reported anticancer activity of erianin. All updated valuable information regarding the underlying action mechanisms of erianin in specific cancer was recorded and summarized in this paper. Most importantly, based on the molecular structure of erianin, its potential molecular targets were analyzed and predicted by means of the SwissTargetPrediction online server (http://www.swisstargetprediction.ch). In the meantime, the potential therapeutic targets of 10 types of cancers in which erianin has been proved to have anticancer effects were also predicted via the Online Mendelian Inheritance in Man (OMIM) database (http://www.ncbi.nlm.nih.gov/omim). The overlapping targets may serve as valuable target candidates through which erianin exerts its anticancer activity. The clinical value of those targets was subsequently evaluated by analyzing their prognostic role in specific cancer using Kaplan-Meier plotter (http://Kmplot.com/analysis/) and Gene Expression Profiling Interactive Analysis (GEPIA) (http://gepia.cancer-pku.cn/). To better assess and verify the binding ability of erianin with its potential targets, molecular flexible docking was performed using Discovery Studio (DS). The valuable targets obtained from the above analysis and verification were further mapped to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway using the Database for Annotation, Visualization and Integrated Discovery (DAVID) (http://david.abcc.ncifcrf.gov/) to explore the possible signaling pathways disturbed/regulated by erianin. Furthermore, the in silico prediction of absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of erianin was also performed and provided in this paper. Overall, in this study, we aimed at 1) collecting all experiment-based important information regarding the anticancer effect and pharmacological mechanism of erianin, 2) providing the predicted therapeutic targets and signaling pathways that erianin might act on in cancers, and 3) especially providing in silico ADMET properties of erianin.
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Affiliation(s)
- Lili Yan
- School of Pharmacy, Hangzhou Normal University, Hangzhou, China
- 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, China
| | - Zhen Zhang
- Department of Orthopedic Surgery, Hangzhou Orthopedic Institute, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yanfen Liu
- School of Pharmacy, Hangzhou Normal University, Hangzhou, China
- 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, China
| | - Shuyi Ren
- School of Pharmacy, Hangzhou Normal University, Hangzhou, China
- 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, China
| | - Zhiyu Zhu
- School of Pharmacy, Hangzhou Normal University, Hangzhou, China
- 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, China
| | - Lu Wei
- School of Pharmacy, Hangzhou Normal University, Hangzhou, China
- 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, China
| | - Jiao Feng
- School of Pharmacy, Hangzhou Normal University, Hangzhou, China
- 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, China
| | - Ting Duan
- School of Pharmacy, Hangzhou Normal University, Hangzhou, China
- 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, China
| | - Xueni Sun
- School of Pharmacy, Hangzhou Normal University, Hangzhou, China
- 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, China
- *Correspondence: Xueni Sun, ; Tian Xie, ; Xinbing Sui,
| | - Tian Xie
- School of Pharmacy, Hangzhou Normal University, Hangzhou, China
- 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, China
- *Correspondence: Xueni Sun, ; Tian Xie, ; Xinbing Sui,
| | - Xinbing Sui
- School of Pharmacy, Hangzhou Normal University, Hangzhou, China
- 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, China
- *Correspondence: Xueni Sun, ; Tian Xie, ; Xinbing Sui,
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Wu SS, Hao LJ, Shi YY, Lu ZJ, Yu JL, Jiang SQ, Liu QL, Wang T, Guo SY, Li P, Li F. Network Pharmacology-Based Analysis on the Effects and Mechanism of the Wang-Bi Capsule for Rheumatoid Arthritis and Osteoarthritis. ACS OMEGA 2022; 7:7825-7836. [PMID: 35284738 PMCID: PMC8908527 DOI: 10.1021/acsomega.1c06729] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 01/26/2022] [Indexed: 06/12/2023]
Abstract
Wang-Bi capsule (WB) is a traditional Chinese medicine (TCM)-based herbal formula, and it has been used in the treatment of rheumatoid arthritis (RA) in China for many years. Additionally, WB is also used as a supplement to the treatment of osteoarthritis (OA) in clinical practice. Our research aimed to reveal the therapeutic effects and underling mechanism of WB on RA and OA through computational system pharmacology analysis and experimental study. Based on network pharmacology analysis, a total of 173 bioactive compounds interacted with 417 common gene targets related to WB, RA, and OA, which mainly involved the PI3K-Akt signaling pathway. In addition, the serine-threonine protein kinase 1 (AKT1) might be a core gene protein for the action of WB, which was further emphasized by molecular docking. Moreover, the anti-inflammatory activity of WB in vitro was confirmed by reducing NO production in lipopolysaccharide (LPS)-induced RAW264.7 cells. The anti-RA and OA effects of WB in vivo were confirmed by ameliorating the disease symptoms of collagen II-induced RA (CIA) and monosodium iodoacetate-induced OA (MIA) in rats, respectively. Furthermore, the role of the PI3K-Akt pathway in the action of WB was preliminarily verified by western blot analysis. In conclusion, our study elucidated that WB is a potentially effective strategy for the treatment of RA and OA, which might be achieved by regulating the PI3K-Akt pathway. It provides us with systematic insights into the effects and mechanism of WB on RA and OA.
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Affiliation(s)
- Shan-Shan Wu
- State
Key Laboratory of Natural Medicines, China
Pharmaceutical University, Nanjing 210009, China
| | - Li-Jun Hao
- School
of Science, China Pharmaceutical University, Nanjing 210009, China
| | - Yuan-Yuan Shi
- State
Key Laboratory of Natural Medicines, China
Pharmaceutical University, Nanjing 210009, China
- College
of Pharmacy, Xinjiang Medical University, Urumqi 830011, China
| | - Zhuo-Jian Lu
- State
Key Laboratory of Natural Medicines, China
Pharmaceutical University, Nanjing 210009, China
- College
of Pharmacy, Xinjiang Medical University, Urumqi 830011, China
| | - Jia-Lin Yu
- State
Key Laboratory of Natural Medicines, China
Pharmaceutical University, Nanjing 210009, China
| | - Si-Qi Jiang
- State
Key Laboratory of Natural Medicines, China
Pharmaceutical University, Nanjing 210009, China
| | - Qing-Ling Liu
- State
Key Laboratory of Natural Medicines, China
Pharmaceutical University, Nanjing 210009, China
| | - Ting Wang
- School
of Chinese Materia Medica and Yunnan Key Laboratory of Southern Medicinal
Resource, Yunnan University of Chinese Medicine, Kunming 650000, China
| | - Shi-Ying Guo
- China
Resources Sanjiu Medical & Pharmaceutical Company Ltd., Shenzhen 518110, China
| | - Ping Li
- State
Key Laboratory of Natural Medicines, China
Pharmaceutical University, Nanjing 210009, China
| | - Fei Li
- State
Key Laboratory of Natural Medicines, China
Pharmaceutical University, Nanjing 210009, China
- College
of Pharmacy, Xinjiang Medical University, Urumqi 830011, China
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