A network pharmacology study on the main active constituents and key pharmacological pathways of Shaoyao Gancao Decoction on Osteoarthritis
LI Qiuyue, HOU Chengzhi, …, WEI Xu*
[Abstract]Objective This study identifies the active constituents and molecular mechanism of Shaoyao Gancao decoction (SGD) in the treatment of osteoarthritis (OA) and provides new ideas and targets for the prevention and treatment of OA with traditional Chinese medicine (TCM).
Methods The chemical constituent profile of SGD was identified by UHPLC-Q-TOF assay. Based on the candidate active compounds, combining LC-MS with the TCM database, putative targets of SGD drug-like chemical constituents were predicted using TCMSP. The targets of disease were obtained from the Gene database. Subsequently, the compound-target network was constructed and the core potential targets were screened out by a Cytoscape plug-in.
Results Thirty-two bioactive compounds of 87 drug-like chemical constituents of SGD were identified by UHPLC-Q-TOF: 279 genes were found to be the putative targets of these compounds. In a protein-protein interaction (PPI) network, according to the comprehensive analysis of the topological parameters, 62 key targets were found. Subsequently, 23 core genes were further screened out by the cytohubba plug-in of Cytoscape resulting from a synthesis of 11 algorithms. Functional enrichment analysis suggested that SGD exerted its pharmacological effects in OA by modulating multiple pathways. Eighteen active components, 23 key targets and eight key regulatory pathways were identified, among which, CCND1, MYC, MAPK8, INS, EGF, serpine1, and AGE-RAGE signaling pathway are new targets (non-OA genes) and new mechanisms. Conclusion This study systematically and comprehensively studied bioactive compounds and core targets and pathways of SGD on OA by LC-MS-MS and network pharmacology. These results suggest that SGD is likely to treat OA by regulating metabolic pathways, which provides important information and direction for further research.
[Key words] Shaoyao Gancao Decoction (SGD); Osteoarthritis (OA); Network Pharmacology; Pharmacological pathways
基于网络药理学的芍药甘草汤治疗骨关节炎的主要活性成分鉴定及关键药理途径研究
[摘要]目的 研究芍药甘草汤(SGD)治疗骨关节炎(OA)的活性成分及分子机制，为中医药防治OA提供新思路和新靶点。方法 采用UHPLC-Q-TOF法对其进行化学成分鉴定。基于候选活性化合物，结合LC-MS和TCM数据库，利用TCMSP预测SGD药物样化学成分的推定靶标。从基因数据库中获得疾病靶点。构建了化合物-靶标网络，并通过Cytoscape插件筛选出核心潜在靶标。结果 经UHPLC-Q-TOF鉴定，鉴定出32种活性化合物，其中279个基因为这些化合物的靶基因。在蛋白质-蛋白质相互作用(PPI)网络中，根据拓扑参数的综合分析，发现62个关键靶点。利用Cytoscape的cytohubba插件，合成了11种算法，进一步筛选出23个核心基因。功能富集分析表明SGD通过调节多种途径发挥其在OA中的药理作用。其中，CCND1、MYC、MAPK8、INS、EGF、serpine1和age - age signaling pathway是新的靶点(非OA基因)和新的机制。结论 本研究采用LC-MS-MS和网络药理学方法，系统、全面地研究了SGD对OA的生物活性化合物及核心靶点和通路。结果提示SGD可能通过调节代谢途径治疗OA，为开展进一步研究提供了重要参考。
[关键词]芍药甘草汤; 骨关节炎(OA); 网络药理学; 药理通路
