Department of Hand and Foot Surgery, Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China.
Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing, China.
Allergol Immunopathol (Madr). 2021 Nov 1;49(6):16-30. doi: 10.15586/aei.v49i6.484. eCollection 2021.
Guizhi Jia Shaoyao decoction (GSD) is widely used in the clinical treatment of knee osteoarthritis (KOA). However, the underlying molecular mechanisms remain unclear. The aim of this study was to explore functional mechanisms of GSD in treating KOA by utilizing network pharmacology-based approaches.
Candidate components and targets of GSD were retrieved from the Traditional Chinese Medicine Systems Pharmacology database. NCBI, Genecards, Drugbank, and Therapeutic Target Database (TTD) were used to establish a target database for KOA. Then, an interactive network diagram of "drugs-active components-targets" was plotted with Cytoscape open source bioinformatics software. A protein-protein interaction network was constructed and related protein interaction relationships were analyzed based on the STRING database. Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway-enrichment analysis were conducted based on intersected targets. Molecular docking provided an assessment tool for verifying binding of components and targets. It was performed by AutoDock molecular modeling simulation software.
In all, 103 active components were successfully identified, and corresponding 133 targets were searched for treating KOA. Functional enrichment analysis suggested that GSD exerts its pharmacological effect in treating KOA by regulating multiple pathways, such as PI3K-Akt, tumor necrosis factor, Toll-like receptor (TLR), and nuclear factor kappa B signaling pathways. Molecular docking analysis depicted that representative components bound firmly to key targets.
This study revealed the synergistic effects of multiple components, targets, and pathways of GSD for treating KOA. This would enhance the understanding of potential molecular mechanisms of GSD for treating KOA and lay a foundation for further experimental research.
桂枝加芍药生姜各一两人参三两新加汤（GSD）广泛用于膝骨关节炎（KOA）的临床治疗。然而，其潜在的分子机制尚不清楚。本研究旨在利用网络药理学方法探讨 GSD 治疗 KOA 的功能机制。
从中药系统药理学数据库中检索 GSD 的候选成分和靶点。利用 NCBI、Genecards、Drugbank 和治疗靶点数据库（TTD）建立 KOA 靶点数据库。然后，使用 Cytoscape 开源生物信息学软件绘制“药物-活性成分-靶点”相互作用网络图。根据 STRING 数据库构建蛋白质-蛋白质相互作用网络，并分析相关蛋白质相互作用关系。基于交集靶点进行基因本体分析和京都基因与基因组百科全书通路富集分析。通过 AutoDock 分子建模模拟软件进行分子对接，为验证成分与靶点的结合提供评估工具。
共成功鉴定出 103 种活性成分，搜索到 133 个用于治疗 KOA 的靶点。功能富集分析表明，GSD 通过调节 PI3K-Akt、肿瘤坏死因子、Toll 样受体（TLR）和核因子 kappa B 信号通路等多种途径发挥治疗 KOA 的药理作用。分子对接分析表明，代表性成分与关键靶点结合牢固。
本研究揭示了 GSD 治疗 KOA 的多成分、靶点和通路的协同作用。这将有助于深入了解 GSD 治疗 KOA 的潜在分子机制，并为进一步的实验研究奠定基础。
