Wang Yulin, Zhang Jiahao, Liu Junzheng, Liu Tun, Zhao Jiaxin, Guo Yiling, Zhang Xinyi, Wang Wei
Department of Orthopaedics, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Curr Pharm Des. 2025 Feb 28. doi: 10.2174/0113816128330436250210052548.
Zuo Gui pill (ZGP) is a herbal compound formulation used to treat knee osteoarthritis (KOA), but its underlying mechanisms are still unclear. This study aimed to initially elucidate the molecular mechanisms of ZGP in treating KOA using network pharmacology and molecular docking techniques.
We collected information on the drug compounds and targets from TCMSP, HERB, BATMANTCM, and UniProt databases, as well as the KOA-related targets from DisGeNET, GeneCards, OMIM, and GEO databases. Afterward, we obtained the hub targets of ZGP and KOA. The biological processes and major pathways of the hub targets were analyzed by GO and KEGG, and three networks were constructed to illustrate the mechanisms of ZGP for the treatment of KOA. Finally, molecular docking was carried out to verify the binding of the main compounds to the key targets.
Through the network pharmacological analysis, we screened important compounds in ZGP, such as quercetin, kaempferol, wogonin, isorhamnetin, and 138 hub targets, including PTGS2, NOS3, AKT1, MAPK1, which are enriched in PI3K-Akt, MAPK, TNF, IL-17, HIF-1, and other signaling pathways. The molecular docking results showed that the main compounds and key targets have high affinity, which further demonstrated the molecular mechanisms and provided a basis for the clinical application of ZGP.
This study illustrates the specific mechanisms of ZGP in the treatment of KOA using network pharmacology and molecular docking techniques, which lays the foundation for further research on its pharmacological mechanisms.
左归丸（ZGP）是一种用于治疗膝关节骨关节炎（KOA）的中药复方制剂，但其潜在机制仍不清楚。本研究旨在利用网络药理学和分子对接技术初步阐明ZGP治疗KOA的分子机制。
我们从中药系统药理学数据库与分析平台（TCMSP）、中药综合数据库（HERB）、中药系统药理学数据库（BATMAN-TCM）和通用蛋白质数据库（UniProt）收集药物化合物和靶点信息，以及从疾病基因数据库（DisGeNET）、基因卡片数据库（GeneCards）、在线孟德尔人类遗传数据库（OMIM）和基因表达综合数据库（GEO）收集KOA相关靶点。之后，我们获得了ZGP和KOA的核心靶点。通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析核心靶点的生物学过程和主要通路，并构建三个网络以阐明ZGP治疗KOA的机制。最后，进行分子对接以验证主要化合物与关键靶点的结合。
通过网络药理学分析，我们筛选出ZGP中的重要化合物，如槲皮素、山奈酚、汉黄芩素、异鼠李素，以及138个核心靶点，包括环氧化酶-2（PTGS2）、一氧化氮合酶3（NOS3）、蛋白激酶B1（AKT1）、丝裂原活化蛋白激酶1（MAPK1），这些靶点富集于磷脂酰肌醇-3激酶-蛋白激酶B（PI3K-Akt）、丝裂原活化蛋白激酶（MAPK）、肿瘤坏死因子（TNF）、白细胞介素-17（IL-17）、缺氧诱导因子-1（HIF-1）等信号通路。分子对接结果表明主要化合物与关键靶点具有高亲和力进一步证明了分子机制，并为ZGP的临床应用提供了依据。
本研究利用网络药理学和分子对接技术阐明了ZGP治疗KOA的具体机制，为进一步研究其药理机制奠定了基础。
