Department of Orthopedics, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China.
State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asian Xinjiang, Key Laboratory of Echinococcosis, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China.
Discov Med. 2020 Sep-Oct;30(160):83-95.
Traditional Chinese medicine Salvia miltiorrhiza (SM) is a novel application and has shown significant clinical efficacy in treating osteoarthritis (OA). However, the molecular mechanisms of its action have not been systematically evaluated. This study explores the mechanisms of SM in the treatment of osteoarthritis using a network pharmacology approach. In this study, the active ingredients and related targets of SM were obtained following an ADME (absorption, distribution, metabolism, excretion) approach and utilizing the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. OA-related targets were obtained through GeneCard, PharmGkb, TTD, OMIM, and DRUGBANK databases. The common targets were obtained using the jvenn online tool. The ingredient-target network and the crucial active ingredients were obtained by Cytoscape. The protein-protein interaction (PPI) network and the key targets of SM in the treatment of OA were obtained by the STRING database and Cytoscape. The GO function and KEGG pathway enrichment cluster of the common targets were obtained by Metascape. Molecular docking was obtained by SwissDock to verify the correlation between the crucial active ingredients and key targets. We identified 59 active ingredients including luteolin, tanshinone IIA, dihydrotanshinquinone, and danshenxinkun D with important biological effects in the treatment of OA. We screened 72 common targets of SM-OA, among which IL-6, AKT1, VEGFA, TNF, TP53, FOS, MAPK1, and CASP3 are the key targets. The GO function and KEGG pathway enrichment cluster of the common targets revealed that SM acts on OA mainly through the PI3K-AKT, IL-17, HIF-1, and TNF signaling pathways and that its function is mainly to regulate metabolism, apoptosis, inflammation, and cell proliferation. Moreover, the molecular docking analysis indicated that the crucial ingredients were tightly bound to the key targets. Overall, our study has preliminarily revealed the molecular mechanisms of SM in the treatment of OA through multi-component, multi-target, and multi-channel network pharmacology approaches.
传统中药丹参（SM）是一种新的应用，在治疗骨关节炎（OA）方面显示出显著的临床疗效。然而，其作用的分子机制尚未得到系统评估。本研究采用网络药理学方法探讨 SM 治疗 OA 的机制。在这项研究中，通过 ADME（吸收、分布、代谢、排泄）方法和利用中药系统药理学（TCMSP）数据库获得 SM 的活性成分和相关靶点。通过 GeneCard、PharmGkb、TTD、OMIM 和 DRUGBANK 数据库获得 OA 相关靶点。使用 jvenn 在线工具获得共同靶点。通过 Cytoscape 获得成分-靶点网络和 SM 治疗 OA 的关键活性成分。通过 STRING 数据库和 Cytoscape 获得 SM 治疗 OA 的蛋白质-蛋白质相互作用（PPI）网络和关键靶点。通过 Metascape 获得共同靶点的 GO 功能和 KEGG 途径富集簇。通过 SwissDock 进行分子对接，以验证关键活性成分与关键靶点之间的相关性。我们确定了 59 种具有重要生物效应的活性成分，包括木犀草素、丹参酮 IIA、二氢丹参醌和丹参新醌 D，用于治疗 OA。我们筛选了 SM-OA 的 72 个共同靶点，其中 IL-6、AKT1、VEGFA、TNF、TP53、FOS、MAPK1 和 CASP3 是关键靶点。共同靶点的 GO 功能和 KEGG 途径富集簇表明，SM 主要通过 PI3K-AKT、IL-17、HIF-1 和 TNF 信号通路作用于 OA，其功能主要是调节代谢、凋亡、炎症和细胞增殖。此外，分子对接分析表明，关键成分与关键靶点紧密结合。总之，我们的研究通过多成分、多靶点、多通道网络药理学方法，初步揭示了 SM 治疗 OA 的分子机制。
