基于网络药理学和分子对接探究威灵仙治疗类风湿性关节炎的作用机制

doi:10.3976/j.issn.1002-4026.2022.06.006

山东科学 ›› 2022, Vol. 35 ›› Issue (6): 42-49.doi: 10.3976/j.issn.1002-4026.2022.06.006

基于网络药理学和分子对接探究威灵仙治疗类风湿性关节炎的作用机制

蒋叶坷¹^,²(), 陈燕¹^,², 潘凌宇¹, 韩燕全¹, 何宁², 汪永忠¹^,^*()

1.安徽中医药大学第一附属医院国家中医药管理局中药制剂三级实验室中药复方安徽省重点实验室现代药物制剂安徽省工程技术中心,安徽合肥230031
2.安徽中医药大学药学院,安徽合肥 230012

收稿日期:2021-09-08 出版日期:2022-12-20 发布日期:2022-12-02
通信作者: 汪永忠 E-mail:1466989029@qq.com;wyzhmail@163.com
作者简介:蒋叶坷(1995—),女,硕士研究生。研究方向为中药新药研究与开发。Tel:18856093532;E-mail:1466989029@qq.com
基金资助:
安徽省高等学校自然科学研究项目(KJ2019A0440);安徽省高等学校自然科学研究项目(KJ2020A0409)

Mechanism of Clematidis Radix Rhizoma in the treatment of rheumatoid arthritis based on network pharmacology and molecular docking

JIANG Ye-ke¹^,²(), CHEN Yan¹^,², PAN Ling-yu¹, HAN Yan-quan¹, HE Ning², WANG Yong-zhong¹^,^*()

1. The Third Level Laboratory of Traditional Chinese Medicine Preparations of State Administration of Chinese Medicine Anhui Engineering Technology Center of Modern Pharmaceutical Preparations,Anhui Key Laboratory of Chinese Herbal Compound, The First Affiliated Hospital of Anhui University of Chinese Medicine Hefei, Anhui 230031
2. School of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui 230012

Received:2021-09-08 Online:2022-12-20 Published:2022-12-02
Contact: WANG Yong-zhong E-mail:1466989029@qq.com;wyzhmail@163.com

摘要/Abstract

摘要：

运用网络药理学和分子对接方法探究威灵仙治疗类风湿性关节炎的作用机制。中药系统药理学数据库与分析平台、PubChem、SwissTargetPrediction数据库筛选威灵仙的活性成分及其作用靶点;OMIM、GeneCards数据库预测类风湿性关节炎的靶点;Venn图获取威灵仙-类风湿性关节炎的交集靶点;STRING数据库构建蛋白质-蛋白质相互作用网络后导入Cytoscape3.7.1获取核心靶点;DAVID数据库进行基因本体和京都基因与基因组百科全书富集分析; AutoDock Vina1.5.6对关键活性成分和核心靶点进行分子对接验证。威灵仙中的关键活性成分齐墩果酸、β-谷甾醇、豆甾醇、3-表齐墩果酸作用于MAPK3、PTGS2、CYP19A1等核心靶点,通过调控花生四烯酸代谢通路、卵巢类固醇生成等发挥治疗类风湿性关节炎的作用,分子对接结果显示关键活性成分与核心靶点具有较好的结合活性。该研究初步探讨了威灵仙治疗类风湿性关节炎的关键活性成分、核心作用靶点及其相关通路,为威灵仙的临床应用提供参考。

关键词: 威灵仙, 网络药理学, 类风湿性关节炎, 分子对接, 作用机制

Abstract:

This study aimed to explore the mechanism of Clematidis Radix Rhizoma in the treatment of rheumatoid arthritis based on network pharmacology and molecular docking. Traditional Chinese medicine systems pharmaclogy database and analysis platform database, PubChem, and SwissTargetPrediction database were used to screen the active ingredients of Clematidis Radix Rhizoma and their targets. The targets of rheumatoid arthritis were predicted using OMIM database and GeneCards database. Venn diagram was used to obtain the intersection targets of Clematidis Radix Rhizoma and rheumatoid arthritis. Protein interaction network was constructed using STRING database and imported into Cytoscape3.7.1 to obtain core targets. DAVID database was used for Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis. AutoDock Vina1.5.6 was employed to perform molecular docking of key active ingredients and core targets. The key active ingredients in Clematidis Radix Rhizoma, such as oleanolic acid, β-sitosterol, stigmasterol, and 3-epioleanolic acid, act on core targets, such as MAPK3, PTGS2, and CYP19A1, and play a role in the treatment of rheumatoid arthritis by regulating arachidonic acid metabolic pathway and ovarian steroidogenesis. The result of molecular docking suggested that the key active ingredients had good binding activity with the core targets. In this paper, the key active ingredients, core targets, and related pathways of Clematidis Radix Rhizoma in the treatment of rheumatoid arthritis were preliminarily discussed, serving as a reference for clinical application of Clematidis Radix Rhizoma.

Key words: Clematidis Radix Rhizoma, network pharmacology, rheumatoid arthritis, molecular docking, mechanism

中图分类号:

R285

蒋叶坷, 陈燕, 潘凌宇, 韩燕全, 何宁, 汪永忠. 基于网络药理学和分子对接探究威灵仙治疗类风湿性关节炎的作用机制[J]. 山东科学, 2022, 35(6): 42-49.

JIANG Ye-ke, CHEN Yan, PAN Ling-yu, HAN Yan-quan, HE Ning, WANG Yong-zhong. Mechanism of Clematidis Radix Rhizoma in the treatment of rheumatoid arthritis based on network pharmacology and molecular docking[J]. Shandong Science, 2022, 35(6): 42-49.

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参考文献 24

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数据库名称	网址
TCMSP	https://tcmsp-e.com/
PubChem	https://pubchem.ncbi.nlm.nih.gov
Swiss Target Prediction	http://www.swisstargetprediction.ch/
OMIM	https://www.omim.org
GeneCards	https://www.genecards.org
STRING	https://string-db.org
DAVID	https://david.ncifcrf.gov
ZINC	http://zinc.docking.org
PDB	https://www.rcsb.org

分子编号	活性成分(Active ingredients)	OB/%	DL
MOL001663	3-表齐墩果酸(3-Epioleanolic acid)	32.03	0.76
MOL002372	角鲨烯(Squalene)	33.55	0.42
MOL000358	β-谷甾醇(Beta-sitosterol)	36.91	0.75
MOL000449	豆甾醇(Stigmasterol)	43.83	0.76
MOL005598	恩比宁(Embinin)	33.91	0.73
MOL005603	邻苯二甲酸庚酯(Heptyl phthalate)	42.26	0.31
MOL000263	齐墩果酸(Oleanolic acid)	29.02	0.76

PDB编号	核心靶点	关键活性成分	结合自由能/(kJ·mol^-1)
6GES	MAPK3	齐墩果酸	-8.5
5KIR	PTGS2	齐墩果酸	-9.1
5KIR	PTGS2	3-表齐墩果酸	-8.4
3S79	CYP19A1	β-谷甾醇	-8.3
		豆甾醇	-8.1
		齐墩果酸	-8.3
3H0A	PPARG	齐墩果酸	-8.0
		β-谷甾醇	-8.1
		豆甾醇	-7.0
1NHZ	NR3C1	齐墩果酸	-8.3
1NHZ	NR3C1	3-表齐墩果酸	-7.8
3V92	ALOX5	齐墩果酸	-9.9
3V92	ALOX5	3-表齐墩果酸	-9.3

基于网络药理学和分子对接探究威灵仙治疗类风湿性关节炎的作用机制

Mechanism of Clematidis Radix Rhizoma in the treatment of rheumatoid arthritis based on network pharmacology and molecular docking

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