| 朱珊珊,汪洋,张奇,秦路平,张巧艳.基于网络药理学及分子生物学验证探讨畲药黄荆条黄酮类成分抗类风湿关节炎的作用机制[J].浙江中西医结合杂志,2022,32(7): |
| 基于网络药理学及分子生物学验证探讨畲药黄荆条黄酮类成分抗类风湿关节炎的作用机制 |
| Mechanisms of Flavonoids from Vitex negundo L. var. cannabifolia in Treatment of Rheumatoid?Arthritis Based on Network Pharmacology and Molecular Biology |
| 投稿时间：2021-11-28 修订日期：2022-05-31 |
| DOI： |
| 中文关键词: 黄荆条 黄酮类 黄荆条醇提物 木犀草素 类风湿性关节炎 网络药理学 分子生物学 |
| 英文关键词:Vitex negundo L. var. Cannabifolia flavonoids Ethanol extract of HJT Luteolin Rheumatoid?Arthritis Network Pharmacology ? Molecular Biology |
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| 中文摘要: |
| 目的 运用网络药理学及分子生物学验证探讨畲药黄荆条黄酮类成分治疗类风湿关节炎（RA）的作用机制。方法 在中国知网、万方、维普和TCMSP数据库筛选黄荆条的黄酮类成分，通过Swiss Target Prediction平台获取活性成分的靶点；通过Gene Cards和CTD数据库获取RA的治疗靶点；利用Cytoscape软件构建黄荆条抗RA的活性成分-作用靶点网络和蛋白质相互作用（PPI）网络；应用R软件对黄荆条抗RA的作用靶点进行GO功能富集和KEGG通路富集分析；应用Autodock vina软件对关键活性成分和靶点进行分子对接验证。采用Western blot验证黄荆条醇提物（HJT-E）及关键成分木犀草素（LUT）对LPS刺激的RAW264.7细胞MMP9、COX-2和AKT1蛋白的调控作用。结果 共得到活性成分靶点309个，RA治疗靶点455个，黄荆条黄酮类成分抗RA的50个靶点；黄荆条治疗RA的关键黄酮类成分主要有LUT、槲皮素、芹菜素、金合欢素等，关键靶蛋白主要有CASP3、MMP9、PTGS2、AKT1等；GO富集分析及KEGG富集分析表明，黄荆条黄酮类成分可调控多种生物学过程及通路，包括AGE-RAGE信号通路、IL-17信号通路、TNF信号通路等；细胞实验验证结果显示，HJT-E及LUT可通过抑制MMP9、COX-2和AKT1蛋白的表达发挥抗炎作用，证实了本研究中网络药理学分析结果的可靠性。结论 畲药黄荆条黄酮类成分通过多靶点和多途径调控成纤维样滑膜细胞增殖、促进其凋亡及缓解炎症反应以发挥抗RA的作用。 |
| 英文摘要: |
| Objective To explore the mechanisms of Vitex negundo L. var. Cannabifolia（Huangjingtiao, HJT） in treatment of rheumatoid?arthritis (RA) using the network pharmacology and molecular biology. Methods The flavonoids of HJT were searched from CNKI, WANFANG, CQVIP and TCMSP.The targets of the flavonoids were predicted using Swiss Target Prediction tool. The targets on RA were searched on Gene Cards and CTD databases. The active component-target network and PPI network of the flavonoids of HJT on RA were constructed using Cytoscape software. The R was employed for GO function enrichment analysis and KEGG pathway enrichment analysis. The effects of ethanol extract of HJT(HJT-E) and luteolin(LUT) on MMP9, COX-2 and AKT1 in LPS-stimulated RAW264.7 cells were verified using western blot. Results This study identified 309 targets of flavonoids, 455 therapeutic targets of RA, and 50 targets of flavonoids of HJT in RA. Luteolin, quercetin, kaempferol, blumenol C were the core flavonoids, while the CASP3、MMP9、PTGS2、AKT1 were the core genes. The GO and KEGG enrichment analyse revealed that flavonoids of HJT were involved in the regulation of various biological processes and pathways, which mainly involved AGE-RAGE signaling pathway, IL-17 signaling pathway, TNF signaling pathway. The results of cell experiments showed that HJT-E and LUT could play an anti-inflammatory role by inhibiting the expression of MMP9, COX-2 and AKT1 proteins, which confirmed the reliability of results of network pharmacology analysis. Conclusion The flavonoids of HJT play a therapeutic role on RA through multi-target and multi-pathway to regulate the the synovial cell proliferation and apoptosis, and alleviate the inflammatory response. |
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