Chen De-Ta, Shen Xue, Li Yu-Mei, Chen Lin, Pan Yan-Bin, Sheng Xiao-Ping, Rao Wu, Xie Xiao-Liang, Gu Jing-Liang, Zhu Hai-Xia, Fan Tian-You, Qiu Min-Lei
Department of Orthopaedics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China.
Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Comb Chem High Throughput Screen. 2023;26(4):743-755. doi: 10.2174/1386207325666220512000940.
The objective of this study is to analyze and verify the main drug components and targets of "Fuzi-Guizhi" in the treatment of osteoarthritis by using the network pharmacology platform.
The integrated pharmacology of "Fuzi-Guizhi" was analyzed by using the platform of integrated pharmacology of traditional Chinese medicine to explore its mechanism in the treatment of osteoarthritis. By establishing an arthritis model in vitro, the pharmacological effect of "aconitecassia twigs" on articular cartilage was evaluated and conducted for molecular docking.
28 candidate active components, 37 compound targets, and 583 osteoarthritis-related potential targets were screened, and 10 key target processes were screened in the protein interaction network model. Enrichment analysis showed that the 10 core targets involved 958 GO biologic function items and 76 KEGG signal pathways, which were mainly related to apoptosis and mitochondrial functional metabolism and "Fuzi-Guizhi" drug-containing serum inhibited the expression of Caspase-3 mRNA and protein in chondrocytes and promoted the synthesis of ATP.
Our research is preliminary that the mechanism of action of "Fuzi-Guizhi" may inhibit chondrocyte degeneration by resisting mitochondrial apoptosis, and further experimental research is required to determine.
本研究旨在利用网络药理学平台分析并验证“附子-桂枝”治疗骨关节炎的主要药物成分及靶点。
运用中药整合药理学平台分析“附子-桂枝”的整合药理学,探讨其治疗骨关节炎的机制。通过建立体外关节炎模型,评价“附子桂枝”对关节软骨的药理作用并进行分子对接。
筛选出28个候选活性成分、37个化合物靶点和583个骨关节炎相关潜在靶点,在蛋白质相互作用网络模型中筛选出10个关键靶标过程。富集分析表明,10个核心靶点涉及958个GO生物学功能条目和76条KEGG信号通路,主要与凋亡和线粒体功能代谢相关,含“附子-桂枝”药物血清抑制软骨细胞中Caspase-3 mRNA和蛋白表达并促进ATP合成。
我们的研究初步表明,“附子-桂枝”的作用机制可能是通过抵抗线粒体凋亡来抑制软骨细胞退变,尚需进一步实验研究加以确定。