YANG Xin, LI Ya-hui, QIAN Hai-bing, et al. Molecular Mechanism of Ursolic Acid Against Rheumatoid Arthritis Based on Network Pharmacology and Molecular Docking[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(18): 207-214.
YANG Xin, LI Ya-hui, QIAN Hai-bing, et al. Molecular Mechanism of Ursolic Acid Against Rheumatoid Arthritis Based on Network Pharmacology and Molecular Docking[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(18): 207-214. DOI: 10.13422/j.cnki.syfjx.20181828.
目的:通过网络药理学及分子对接探讨熊果酸抗类风湿性关节炎的分子机制。方法:基于毒性与基因比较数据库(comparative toxicogenomics database,CTD),Drug Bank数据库,中药系统药理学数据库和分析平台(traditional Chinese medicine systems pharmacology,TCMSP)等检索熊果酸的潜在治病靶点。通过DAVID生物信息学资源(DAVID bioinformatics resources)数据库对潜在靶点进行通路富集分析,STRING进行蛋白相互作用,采用分子对接技术(iGEMDOCK,SystemsDock)对熊果酸和类风湿性关节炎靶标蛋白进行能量匹配。筛选发挥抗类风湿性关节炎作用的潜在靶点。结果:收集相关靶标蛋白66个,DAVID通路富集得到27条信号通路(P<0.01),其中类风湿性关节炎通路关键靶标蛋白11个(基质金属蛋白酶-1,基质金属蛋白酶-3,白细胞介素-6,转录因子AP-1,肿瘤坏死因子,血管内皮生长因子A,集落刺激因子-2,白细胞介素-1β,转化生长因子-β1,细胞黏附分子-1,原癌基因蛋白c-Fos)。通过蛋白相互作用发现有4个靶标蛋白具有实验数据支持。通过分子对接表明熊果酸主要通过基质金属蛋白酶-1,基质金属蛋白酶-3,肿瘤坏死因子,转录因子AP-1,白细胞介素-1β发挥抗类风湿性关节炎的作用。结论:本研究结果初步揭示熊果酸抗类风湿性关节炎的分子机制。
Abstract
Objective: To investigate the molecular mechanism of ursolic acid (UA)against rheumatoid arthritis based on network pharmacology and molecular docking. Method: Potential therapeutic targets of UA were searched based on comparative toxicogenomics database(CTD)
Drug Bank
traditional Chinese medicine systems pharmacology(TCMSP) and other databases. Pathway enrichment analysis of potential targets was conducted by DAVID(DAVID bioinformatics resources). Protein interaction was conducted by STRING
and energy matching between UA and 11 rheumatoid targets was done by molecular docking technique(iGEMDOCK
SystemsDock). The potential targets against rheumatoid arthritis were screened. Result: 66 corresponding targets were collected
and 27 signal pathways were obtained from the enrichment of DAVID pathway (P<0.01)
including 11 key targets proteins in rheumatoid arthritis pathway (matrix metalloproteinase-1
matrix metalloproteinase-3
interleukin-6
transcription factor AP-1
tumor necrosis factor
vascular endothelial growth factor A
granulocyte-macrophage colony-stimulating factor
interleukin-1 beta
transforming growth factor beta-1
and proto-oncogene c-Fos). Through protein interaction
four target proteins were found to be supported by experimental data. The molecular docking showed that UA could resist rheumatoid arthritis mainly through matrix metalloproteinase-1
Matrix metalloproteinase-3
tumor necrosis factor
transcription factor AP-1 and interleukin-1 beta. Conclusion: The results of this study reveal the molecular mechanism of UA against rheumatoid arthritis。