基于网络药理学与分子对接探讨藏族药浴基础组方五味甘露治疗膝关节炎的作用机制  

Mechanism of Wuwei Ganlu in treatment of knee osteoarthritis:a study based on network pharmacology and molecular docking

作　　者：更桑 马婧 任越 贡巴加 才让南加 李贡宇[2] 顿珠 张燕玲[2] GENG Sang;MA Jing;REN Yue;GONG Ba-jia;CAI Rang-nan-jia;LI Gong-yu;DUN Zhu;ZHANG Yan-ling(University of Tibetan Medicine,Lasa 850000,China;Beijing University of Chinese Medicine,Beijing 102488,China)

机构地区：[1]西藏藏医药大学,西藏拉萨850000 [2]北京中医药大学,北京102488

出　　处：《中国中药杂志》2021年第16期4238-4243,共6页China Journal of Chinese Materia Medica

基　　金：西藏自治区藏医药管理局局级项目(JJKT201909);西藏自治区科技计划项目重大科技专项(XZ201801-GH-13);2018年国家中医药管理局旺堆名中医传承工作室建设项目。

摘　　要：五味甘露由麻黄、侧柏、具鳞水柏枝、青蒿、烈香杜鹃5味药组成,具有发汗、消炎、止痛、调整黄水、活血通络等药效,在此基础上衍生出多种藏族药浴配方,可用于五脏六腑、关节、皮肤、神经等病症的治疗。现代研究表明五味甘露对膝关节炎(knee osteoarthritis, KOA)具有良好的治疗效果,因此该研究基于网络药理学及分子对接技术对五味甘露治疗膝关节炎的作用机制进行了探讨。首先通过文献挖掘及数据库检索获得五味甘露的化学成分,基于BATMAN-TCM数据库预测成分潜在作用靶点。将五味甘露潜在作用靶点导入STRING数据库获取蛋白互作关系,采用MCODE进行网络功能模块分析,并对模块进行功能注释以解析五味甘露发挥疗效的潜在作用模式。其次,通过DisGeNET数据库收集膝关节炎相关靶点,合并获得五味甘露治疗膝关节炎的交集靶点,分析探讨五味甘露治疗膝关节炎的作用机制。最终选取关键靶点与五味甘露化学成分进行分子对接以验证分析两者的相互作用。研究获得550个五味甘露化学成分,1 365个潜在作用靶点,对五味甘露蛋白互作网络进行模块分析发现方剂可发挥氧化还原、炎症及骨吸收、骨矿化等作用。将五味甘露成分潜在作用靶点与KOA疾病靶点取交集,筛选出交集靶点19个,分析发现五味甘露主要通过作用于核转录因子-κB(nuclear factor-κB,NF-κB)、白细胞介素1β(interleukin^(-1) beta, IL1β)、肿瘤坏死因子(tumor necrosis factor, TNF)、白细胞介素6(interleukin-6,IL6)、白细胞介素1受体拮抗剂(interleukin^(-1) receptor antagonist protein, IL1RN)及前列腺素内过氧化物合酶2(prostaglandin-endoperoxide synthase-2,PTGS2)而发挥治疗KOA作用。以TNF、PTGS2为研究载体,对五味甘露化学成分进行分子对接研究,在五味甘露的550个化学成分中,TNF命中252个潜在活性成分,PTGS2命中163个潜在活性成分,结果显示�Wuwei Ganlu, a formula for medicated bath, consists of medicinal materials of Ephedra sinica, Platycladus orientalis, Myricaria squamosa, Artemisia carvifolia, and Rhododendron anthopogonoides, which is effective in inducing perspiration, resisting inflammation, relieving pain, regulating yellow water disease, and activating blood circulation. On this basis, a variety of formulas for Tibetan medicated bath have been derived for the treatment of diseases in internal organs, joints, nerves, etc. Modern studies have confirmed that Wuwei Ganlu has a good therapeutic efficacy on knee osteoarthritis(KOA). The present study explored the mechanism of Wuwei Ganlu in treating KOA based on network pharmacology and molecular docking. Firstly, the chemical components of Wuwei Ganlu were obtained through literature mining and database retrieval, and corresponding potential targets were predicted according to the BATMAN-TCM database. The protein-protein interaction(PPI) network was obtained after the potential targets were input into the STRING database. The network function modules were analyzed by the Molecular Complex Detection(MCODE) algorithm, and the functions of the modules were annotated to analyze the action mode of Wuwei Ganlu. Secondly, the related targets of KOA were collected through the DisGeNET database, and the overlapping targets were confirmed to analyze the mechanism of Wuwei Ganlu in treating KOA. Finally, the key targets were selected for molecular docking with the main components of Wuwei Ganlu to verify the component-target interaction. A total of 550 chemical components and 1 365 potential targets of Wuwei Ganlu were obtained. PPI analysis indicated that this formula could exert the effects of oxidation-reduction, inflammation resistance, bone absorption, bone mineralization, etc. Nineteen common targets were obtained from the intersection of potential targets of Wuwei Ganlu and KOA disease targets. It was found that the Wuwei Ganlu mainly acts on nuclear factor-κB(NF-κB), interleukin^(-1) beta(IL1β),

关 键 词：五味甘露 藏族药浴 膝关节炎 网络药理学 分子对接 

分 类 号：R29[医药卫生—民族医学]