Department of Rheumatology, the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang 550002, China.
Department of Traditional Chinese Medicine, Longhua District Central Hospital, Shenzhen 518110, China.
J Tradit Chin Med. 2022 Aug;42(4):576-585. doi: 10.19852/j.cnki.jtcm.20220519.002.
To investigate molecular mechanisms of Jinwujiangu decoction (, JWJG) in treating osteoarthritis (OA) using network pharmacology analysis.
Principal active compounds of JWJG were screened out via the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and BATMAN-TCM, and potential targets for OA treatment were identified through Online Mendelian Inheritance in Man (OMIM) and GeneCards databases. The JWJG network diagrams of both principal chemical compound-action targets and OA treatment target-OA disease were constructed applying the Cytoscape 3.7.2 software. The diagram of protein-protein interaction network was plotted for core analysis. Meanwhile, the common targets and relevant signaling pathways involved in both networks were analyzed using the Gene Ontology function analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. The predicted results were ultimately verified through animal experiments.
Effects of JWJG were indicated in acting on key targets interleukin-6, insulin, protein kinase B, glyceraldehyde-3-phosphate dehydrogenase, and mitosis-specific MRE11-RAD50-NBS1 associated protein by regulating signaling pathways of phosphoinositide 3-kinase- protein kinase B, mitogen-activated protein kinases, tumor necrosis factor, and colorectal cancer. Meanwhile, it inhibited the over-activation of signaling pathways and the release of inflammatory factors in OA treatment. Following a signaling pathway analysis utilizing network pharmacology technique, it was demonstrated that JWJG could treat OA through the Wnt/β-catenin signaling pathway verified by animal experiments.
The present study preliminarily analyzed the pharmacological mechanism of JWJG in treating OA on a network pharmacology approach and provided a great theoretical significance for clinical application.
运用网络药理学分析探讨金匮关节炎汤(JWJG)治疗骨关节炎(OA)的分子机制。
通过中药系统药理学数据库和分析平台(TCMSP)和 BATMAN-TCM 筛选 JWJG 的主要活性化合物,并通过在线孟德尔遗传人类(OMIM)和基因卡片数据库识别 OA 治疗的潜在靶点。运用 Cytoscape 3.7.2 软件构建 JWJG 主要化学化合物-作用靶点和 OA 治疗靶点-OA 疾病网络图。绘制蛋白质-蛋白质相互作用网络图进行核心分析。同时,利用基因本体功能分析和京都基因与基因组百科全书通路富集分析对两个网络中共同涉及的靶点和相关信号通路进行分析。最终通过动物实验验证预测结果。
JWJG 通过调节磷酸肌醇 3-激酶-蛋白激酶 B、丝裂原活化蛋白激酶、肿瘤坏死因子和结直肠癌信号通路,对白细胞介素-6、胰岛素、蛋白激酶 B、甘油醛-3-磷酸脱氢酶和有丝分裂特异性 MRE11-RAD50-NBS1 相关蛋白等关键靶点发挥作用,抑制 OA 治疗中信号通路的过度激活和炎症因子的释放。通过网络药理学技术进行信号通路分析表明,JWJG 可通过 Wnt/β-连环蛋白信号通路治疗 OA,这一结论得到了动物实验的验证。
本研究初步采用网络药理学方法分析了 JWJG 治疗 OA 的药理机制,为临床应用提供了重要的理论意义。