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Liu X, Chai R, Xu Q, Zou M, Jiang S, Liu Y, Li R, Kong T, Chen X, Xu R, Liu S, Zhang Z, Liu N. Targeting Skp2 degradation with troxerutin decreases neointima formation. Eur J Pharmacol 2024; 982:176947. [PMID: 39209097 DOI: 10.1016/j.ejphar.2024.176947] [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: 03/23/2024] [Revised: 08/23/2024] [Accepted: 08/26/2024] [Indexed: 09/04/2024]
Abstract
The proliferative and migratory abilities of vascular smooth muscle cells (VSMCs) play a crucial role in neointima formation following vascular injury. Skp2 facilitates proliferation and migration in cells through cell cycle regulation, presenting an important therapeutic target for atherosclerosis, pulmonary hypertension, and vascular restenosis. This study aimed to identify a natural product capable of inhibiting neointima formation post vascular injury. Here, we demonstrate that troxerutin, a flavonoid, significantly reduced viability and downregulated Skp2 in VSMCs. Moreover, troxerutin exhibited anti-proliferative effects on VSMCs and mitigated neointima formation. These findings collectively elucidate the intrinsic mechanism of troxerutin in treating atherosclerosis, pulmonary hypertension, and vascular restenosis by targeting the E3-linked enzyme Skp2.
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MESH Headings
- Hydroxyethylrutoside/analogs & derivatives
- Hydroxyethylrutoside/pharmacology
- S-Phase Kinase-Associated Proteins/metabolism
- S-Phase Kinase-Associated Proteins/antagonists & inhibitors
- Neointima/drug therapy
- Neointima/pathology
- Neointima/metabolism
- Animals
- Cell Proliferation/drug effects
- Muscle, Smooth, Vascular/drug effects
- Muscle, Smooth, Vascular/metabolism
- Muscle, Smooth, Vascular/cytology
- Muscle, Smooth, Vascular/pathology
- Myocytes, Smooth Muscle/drug effects
- Myocytes, Smooth Muscle/metabolism
- Myocytes, Smooth Muscle/pathology
- Proteolysis/drug effects
- Cell Survival/drug effects
- Humans
- Cell Movement/drug effects
- Down-Regulation/drug effects
- Rats
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Affiliation(s)
- Xiaolin Liu
- Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, China
| | - Renjie Chai
- Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, China
| | - Qiong Xu
- Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, China
| | - Min Zou
- Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, China
| | - Siqin Jiang
- Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, China
| | - Yajing Liu
- Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, China
| | - Rongxue Li
- Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, China
| | - Tianyu Kong
- Department of Critical Care Medicine, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, China
| | - Xiaohua Chen
- Department of Critical Care Medicine, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, China
| | - Ruqin Xu
- Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, China
| | - Shiming Liu
- Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, China
| | - Zhenhui Zhang
- Department of Critical Care Medicine, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, China.
| | - Ningning Liu
- Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, China.
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Feng JH, Chen K, Shen SY, Luo YF, Liu XH, Chen X, Gao W, Tong YR. The composition, pharmacological effects, related mechanisms and drug delivery of alkaloids from Corydalis yanhusuo. Biomed Pharmacother 2023; 167:115511. [PMID: 37729733 DOI: 10.1016/j.biopha.2023.115511] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Revised: 09/06/2023] [Accepted: 09/12/2023] [Indexed: 09/22/2023] Open
Abstract
Corydalis yanhusuo W. T. Wang, also known as yanhusuo, yuanhu, yanhu and xuanhu, is one of the herb components of many Chinese Traditional Medicine prescriptions such as Jin Ling Zi San and Yuanhu-Zhitong priscription. C. yanhusuo was traditionally used to relieve pain and motivate blood and Qi circulation. Now there has been growing interest in pharmacological effects of alkaloids, the main bioactive components of C. yanhusuo. Eighty-four alkaloids isolated from C. yanhusuo are its important bioactive components and can be characterized into protoberberine alkaloids, aporphine alkaloids, opiate alkaloids and others and proper extraction or co-administration methods modulate their contents and efficacy. Alkaloids from C. yanhusuo have various pharmacological effects on the nervous system, cardiovascular system, cancer and others through multiple molecular mechanisms such as modulating neurotransmitters, ion channels, gut microbiota, HPA axis and signaling pathways and are potential treatments for many diseases. Plenty of novel drug delivery methods such as autologous red blood cells, self-microemulsifying drug delivery systems, nanoparticles and others have also been investigated to better exert the effects of alkaloids from C. yanhusuo. This review summarized the alkaloid components of C. yanhusuo, their pharmacological effects and mechanisms, and methods of drug delivery to lay a foundation for future investigations.
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Affiliation(s)
- Jia-Hua Feng
- School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China; School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China
| | - Kang Chen
- National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Si-Yu Shen
- School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China
| | - Yun-Feng Luo
- School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China
| | - Xi-Hong Liu
- School of Medicine, Henan University of Chinese Medicine, Zhengzhou 450046, China
| | - Xin Chen
- School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China
| | - Wei Gao
- School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China
| | - Yu-Ru Tong
- School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China.
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Dai XS, Wei QH, Guo X, Ding Y, Yang XQ, Zhang YX, Xu XY, Li C, Chen Y. Ferulic acid, ligustrazine, and tetrahydropalmatine display the anti-proliferative effect in endometriosis through regulating Notch pathway. Life Sci 2023; 328:121921. [PMID: 37429417 DOI: 10.1016/j.lfs.2023.121921] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 06/30/2023] [Accepted: 07/06/2023] [Indexed: 07/12/2023]
Abstract
AIMS With an ambiguous anti-proliferative mechanism, the combination of ferulic acid, ligustrazine, and tetrahydropalmatine (FLT) shows good anti-endometriosis (EMS) activity. In EMS, the expression of Notch pathway and its role in proliferation are not yet unclear. In this study, we sought to uncover the role of Notch pathway's effect and FLT's anti-proliferative mechanism on EMS proliferation. MAIN METHODS In autograft and allograft EMS models, the proliferating markers (Ki67, PCNA), Notch pathway, and the effect of FLT on them were detected. Then, the anti-proliferative influence of FLT was measured in vitro. The proliferating ability of endometrial cells was investigated with a Notch pathway activator (Jagged 1 or VPA) or inhibitor (DAPT) alone, or in combination with FLT separately. KEY FINDINGS FLT presented the inhibitory effect on ectopic lesions in 2 EMS models. The proliferating markers and Notch pathway were promoted in ectopic endometrium, but FLT showed the counteraction. Meantime, FLT restrained the endometrial cell growth and clone formation along with a reduction in Ki67 and PCNA. Jagged 1 and VPA stimulated the proliferation. On the contrary, DAPT displayed the anti-proliferating effect. Furthermore, FLT exhibited an antagonistic effect on Jagged 1 and VPA by downregulating Notch pathway and restraining proliferation. FLT also displayed a synergistic effect on DAPT. SIGNIFICANCE This study indicated that the overexpressing Notch pathway induced EMS proliferation. FLT attenuated the proliferation by inhibiting Notch pathway.
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Affiliation(s)
- Xue-Shan Dai
- College of Pharmaceutical Sciences & Chinese Medicine, Southwest University, Chongqing, China; Chongqing Key Laboratory of New Drug Screening from Traditional Chinese Medicine, Chongqing, China; Engineering Research Center of Coptis Development and Utilization, Ministry of Education, College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing, China; National Demonstration Center for Experimental Pharmacy Education, Southwest University, Chongqing, China
| | - Qing-Hua Wei
- College of Pharmaceutical Sciences & Chinese Medicine, Southwest University, Chongqing, China; Chongqing Key Laboratory of New Drug Screening from Traditional Chinese Medicine, Chongqing, China; Engineering Research Center of Coptis Development and Utilization, Ministry of Education, College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing, China; National Demonstration Center for Experimental Pharmacy Education, Southwest University, Chongqing, China
| | - Xin Guo
- College of Pharmaceutical Sciences & Chinese Medicine, Southwest University, Chongqing, China; Chongqing Key Laboratory of New Drug Screening from Traditional Chinese Medicine, Chongqing, China; Engineering Research Center of Coptis Development and Utilization, Ministry of Education, College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing, China; National Demonstration Center for Experimental Pharmacy Education, Southwest University, Chongqing, China
| | - Yi Ding
- College of Pharmaceutical Sciences & Chinese Medicine, Southwest University, Chongqing, China; Chongqing Key Laboratory of New Drug Screening from Traditional Chinese Medicine, Chongqing, China; Engineering Research Center of Coptis Development and Utilization, Ministry of Education, College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing, China; National Demonstration Center for Experimental Pharmacy Education, Southwest University, Chongqing, China
| | - Xiao-Qian Yang
- College of Pharmaceutical Sciences & Chinese Medicine, Southwest University, Chongqing, China; Chongqing Key Laboratory of New Drug Screening from Traditional Chinese Medicine, Chongqing, China; Engineering Research Center of Coptis Development and Utilization, Ministry of Education, College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing, China; National Demonstration Center for Experimental Pharmacy Education, Southwest University, Chongqing, China
| | - Yu-Xin Zhang
- College of Pharmaceutical Sciences & Chinese Medicine, Southwest University, Chongqing, China; Chongqing Key Laboratory of New Drug Screening from Traditional Chinese Medicine, Chongqing, China; Engineering Research Center of Coptis Development and Utilization, Ministry of Education, College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing, China; National Demonstration Center for Experimental Pharmacy Education, Southwest University, Chongqing, China
| | - Xiao-Yu Xu
- College of Pharmaceutical Sciences & Chinese Medicine, Southwest University, Chongqing, China; Chongqing Key Laboratory of New Drug Screening from Traditional Chinese Medicine, Chongqing, China; Engineering Research Center of Coptis Development and Utilization, Ministry of Education, College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing, China; National Demonstration Center for Experimental Pharmacy Education, Southwest University, Chongqing, China
| | - Cong Li
- Department of Obstetrics & Gynecology, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Yi Chen
- College of Pharmaceutical Sciences & Chinese Medicine, Southwest University, Chongqing, China; Chongqing Key Laboratory of New Drug Screening from Traditional Chinese Medicine, Chongqing, China; Engineering Research Center of Coptis Development and Utilization, Ministry of Education, College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing, China; National Demonstration Center for Experimental Pharmacy Education, Southwest University, Chongqing, China.
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Li YJ, Tang DX, Yan HT, Yang B, Yang Z, Long FX. Network pharmacology and molecular docking-based analyses to predict the potential mechanism of Huangqin decoction in treating colorectal cancer. World J Clin Cases 2023; 11:4553-4566. [PMID: 37469733 PMCID: PMC10353508 DOI: 10.12998/wjcc.v11.i19.4553] [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: 04/24/2023] [Revised: 05/27/2023] [Accepted: 06/13/2023] [Indexed: 06/30/2023] Open
Abstract
BACKGROUND To analyze the potential action mechanism of Huangqin decoction (HQD) in colorectal cancer (CRC) treatment on the basis of network pharmacology and molecular docking.
AIM To investigate the molecular mechanisms of HQD for CRC treatment by using network pharmacology and molecular docking.
METHODS All HQD active ingredients were searched using the Systematic Pharmacology and Traditional Chinese Medicine Systems Pharmacology databases and the Bioinformatics Analysis Tool for Molecular Mechanisms in traditional Chinese medicine. Then, the targets of the active ingredients were screened. The abbreviations of protein targets were obtained from the UniProt database. A “drug–compound–target” network was constructed to screen for some main active ingredients. Some targets related to the therapeutic effect of CRC were obtained from the GeneCards, DisGeNET, Therapeutic Target Database, and Online Mendelian Inheritance in Man databases. The intersection of targets of Chinese herbs and CRC was taken. A Venn diagram was drawn to construct the intersection target interactions network by referring to the STRING database. Topological analysis of the protein interaction network was performed using Cytoscape 3.7.2 software to screen the core HQD targets for CRC. The core targets were imported into the DAVID 6.8 analysis website for gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses and visualization. Finally, molecular docking was performed using AutoDockTool and PyMOL for validation.
RESULTS In total, 280 potential drug-active ingredients were present in HQD, including 1474 targets of the drug-active ingredients. The main active ingredients identified were betulin, tetrahydropalmatine, and quercetin. In total, 10249 CRC-related targets and 1014 drug-disease intersecting targets were identified, including 28 core targets of action such as Jun proto-oncogene, AP-1 transcription factor subunit, signal transducer and activator of transcription 3, tumor protein p53, vascular endothelial growth factor, and AKT serine/threonine kinase 1. The gene ontology enrichment functional analysis yielded 503 enrichment results, including 406 biological processes that were mainly related to the positive regulation of both gene expression and transcription and cellular response to hypoxia, etc. In total, 38 cellular components were primarily related to polymer complexes, transcription factor complexes, and platelet alpha granule lumen. Then, 59 molecular functions were closely related to the binding of enzymes, homologous proteins, and transcription factors. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis yielded 139 enrichment results, involving epidermal growth factor receptor tyrosine kinase inhibitor resistance and HIF-1 and mitogen-activated protein kinase signaling pathways.
CONCLUSION HQD can play a role in CRC treatment through the “multi-component-target–pathway”. The active ingredients betulin, tetrahydropalmatine, and quercetin may act on targets such as Jun proto-oncogene, AP-1 transcription factor subunit, signal transducer and activator of transcription 3, tumor protein p53, vascular endothelial growth factor, and AKT serine/threonine kinase 1, which in turn regulate HIF-1 and mitogen-activated protein kinase signaling pathways in CRC treatment. The molecular docking junction clarified that all four key target proteins could bind strongly to the main HQD active ingredients. This indicates that HQD could slow down CRC progression by modulating multiple targets and signaling pathways.
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Affiliation(s)
- Ying-Jie Li
- Guizhou University of Traditional Chinese Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550005, Guizhou Province, China
| | - Dong-Xin Tang
- Digestive Department, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang 550001, Guizhou Province, China
| | - Hong-Ting Yan
- Guizhou University of Traditional Chinese Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550001, Guizhou Province, China
| | - Bing Yang
- Digestive Department, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang 550001, Guizhou Province, China
| | - Zhu Yang
- Guizhou University of Traditional Chinese Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550001, Guizhou Province, China
| | - Feng-Xi Long
- Guizhou University of Traditional Chinese Medicine, Guizhou University of Traditional Chinese Medicine, Gui Yang 550001, Guizhou Province, China
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Ge Y, Zhan Z, Ye M, Jin X. The crosstalk between ubiquitination and endocrine therapy. J Mol Med (Berl) 2023; 101:461-486. [PMID: 36961537 DOI: 10.1007/s00109-023-02300-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 02/23/2023] [Accepted: 02/26/2023] [Indexed: 03/25/2023]
Abstract
Endocrine therapy (ET), also known as hormone therapy, refers to the treatment of tumors by regulating and changing the endocrine environment and hormone levels. Its related mechanism is mainly through reducing hormone levels and blocking the binding of hormones to corresponding receptors, thus blocking the signal transduction pathway to stimulate tumor growth. However, with the application of ET, some patients show resistance to ET, which is attributed to abnormal accumulation of hormone receptors (HRs) and the production of multiple mutants of HRs. The targeted degradation of abnormal accumulation protein mediated by ubiquitination is an important approach that regulates the protein level and function of intracellular proteins in eukaryotes. Here, we provide a brief description of the traditional and novel drugs available for ET in this review. Then, we introduce the link between ubiquitination and ET. In the end, we elaborate the clinical application of ET combined with ubiquitination-related molecules. KEY MESSAGES: • A brief description of the traditional and novel drugs available for endocrine therapy (ET). • The link between ubiquitination and ET. • The clinical application of ET combined with ubiquitination-related molecules.
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Affiliation(s)
- Yidong Ge
- The Department of Medical Oncology, The First Hospital of Ningbo University, Ningbo University, Ningbo, 315010, China
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Medical School of Ningbo University, Ningbo University, Ningbo, Zhejiang, 315211, China
| | - Ziqing Zhan
- The Department of Medical Oncology, The First Hospital of Ningbo University, Ningbo University, Ningbo, 315010, China
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Medical School of Ningbo University, Ningbo University, Ningbo, Zhejiang, 315211, China
| | - Meng Ye
- The Department of Medical Oncology, The First Hospital of Ningbo University, Ningbo University, Ningbo, 315010, China.
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Medical School of Ningbo University, Ningbo University, Ningbo, Zhejiang, 315211, China.
| | - Xiaofeng Jin
- The Department of Medical Oncology, The First Hospital of Ningbo University, Ningbo University, Ningbo, 315010, China.
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Medical School of Ningbo University, Ningbo University, Ningbo, Zhejiang, 315211, China.
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High-Throughput Sequencing Reveals That Rotundine Inhibits Colorectal Cancer by Regulating Prognosis-Related Genes. J Pers Med 2023; 13:jpm13030550. [PMID: 36983731 PMCID: PMC10052610 DOI: 10.3390/jpm13030550] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 03/13/2023] [Accepted: 03/14/2023] [Indexed: 03/22/2023] Open
Abstract
Background: Rotundine is an herbal medicine with anti-cancer effects. However, little is known about the anti-cancer effect of rotundine on colorectal cancer. Therefore, our study aimed to investigate the specific molecular mechanism of rotundine inhibition of colorectal cancer. Methods: MTT and cell scratch assay were performed to investigate the effects of rotundine on the viability, migration, and invasion ability of SW480 cells. Changes in cell apoptosis were analyzed by flow cytometry. DEGs were detected by high-throughput sequencing after the action of rotundine on SW480 cells, and the DEGs were subjected to function enrichment analysis. Bioinformatics analyses were performed to screen out prognosis-related DEGs of COAD. Followed by enrichment analysis of prognosis-related DEGs. Furthermore, prognostic models were constructed, including ROC analysis, risk curve analysis, PCA and t-SNE, Nomo analysis, and Kaplan–Meier prognostic analysis. Results: In this study, we showed that rotundine concentrations of 50 μM, 100 μM, 150 μM, and 200 μM inhibited the proliferation, migration, and invasion of SW480 cells in a time- and concentration-dependent manner. Rotundine does not induce SW480 cell apoptosis. Compared to the control group, high-throughput results showed that there were 385 DEGs in the SW480 group. And DEGs were associated with the Hippo signaling pathway. In addition, 16 of the DEGs were significantly associated with poorer prognosis in COAD, with MEF2B, CCDC187, PSD2, RGS16, PLXDC1, HELB, ASIC3, PLCH2, IGF2BP3, CLHC1, DNHD1, SACS, H1-4, ANKRD36, and ZNF117 being highly expressed in COAD and ARV1 being lowly expressed. Prognosis-related DEGs were mainly enriched in cancer-related pathways and biological functions, such as inositol phosphate metabolism, enterobactin transmembrane transporter activity, and enterobactin transport. Prognostic modeling also showed that these 16 DEGs could be used as predictors of overall survival prognosis in COAD patients. Conclusions: Rotundine inhibits the development and progression of colorectal cancer by regulating the expression of these prognosis-related genes. Our findings could further provide new directions for the treatment of colorectal cancer.
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Du Q, Meng X, Wang S. A Comprehensive Review on the Chemical Properties, Plant Sources, Pharmacological Activities, Pharmacokinetic and Toxicological Characteristics of Tetrahydropalmatine. Front Pharmacol 2022; 13:890078. [PMID: 35559252 PMCID: PMC9086320 DOI: 10.3389/fphar.2022.890078] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Accepted: 04/06/2022] [Indexed: 11/24/2022] Open
Abstract
Tetrahydropalmatine (THP), a tetrahydroproberine isoquinoline alkaloid, is widely present in some botanical drugs, such as Stephania epigaea H.S. Lo (Menispermaceae; Radix stephaniae epigaeae), Corydalis yanhusuo (Y.H.Chou & Chun C.Hsu) W.T. Wang ex Z.Y. Su and C.Y. Wu (Papaveraceae; Corydalis rhizoma), and Phellodendron chinense C.K.Schneid (Berberidaceae; Phellodendri chinensis cortex). THP has attracted considerable attention because of its diverse pharmacological activities. In this review, the chemical properties, plant sources, pharmacological activities, pharmacokinetic and toxicological characteristics of THP were systematically summarized for the first time. The results indicated that THP mainly existed in Papaveraceae and Menispermaceae families. Its pharmacological activities include anti-addiction, anti-inflammatory, analgesic, neuroprotective, and antitumor effects. Pharmacokinetic studies showed that THP was inadequately absorbed in the intestine and had rapid clearance and low bioavailability in vivo, as well as self-microemulsifying drug delivery systems, which could increase the absorption level and absorption rate of THP and improve its bioavailability. In addition, THP may have potential cardiac and neurological toxicity, but toxicity studies of THP are limited, especially its long-duration and acute toxicity tests. In summary, THP, as a natural alkaloid, has application prospects and potential development value, which is promising to be a novel drug for the treatment of pain, inflammation, and other related diseases. Further research on its potential target, molecular mechanism, toxicity, and oral utilization should need to be strengthened in the future.
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Affiliation(s)
- Qinyun Du
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xianli Meng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,State Key Laboratory of Southwestern Chinese Medicine Resources, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Shaohui Wang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Affiliation(s)
- Jiabing Wang
- Department of Pharmacy, Taizhou Municipal Hospital, Zhejiang, Taizhou, China
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