Zeng Jianwei, Li Cheng, Gu Zuchao
Department of Orthopaedics, Chengdu Integrated TCM and Western Medicine Hospital, Chengdu, China.
Arch Med Sci. 2020 Feb 12;20(2):557-566. doi: 10.5114/aoms.2020.92931. eCollection 2024.
Xianlinggubao (XLGB) capsule is a traditional Chinese medicine, which is approved by the Chinese State Food and Drug Administration (CFDA) for osteoarthritis (OA) and osteoporosis (OP). However, as a capsule with complex ingredients, the molecular mechanisms supporting the therapeutic effects have not been explored.
A network pharmacology-based approach was conducted to explore the complex interactome among the targets of the XLGB active compounds.
The herbs in the capsule contain 41 compounds with 246 high score targets, which cover four known OA targets (PTGS1, PTGS2, PTGER4 and TNF) and six known OP targets (AR, ESR1, PGR, PTGER2, TNFSF11 and VDR) of FDA-approved drugs or drugs undergoing clinical trials. The protein-protein interaction (PPI) network of the 246 targets had six key modules. Among the six modules, neuroactive ligand-receptor interaction, cAMP signaling pathway and calcium signaling pathway are the key pathways, which are all closely associated with the degeneration of joint cartilage and bone formation and resorption.
Neuroactive ligand-receptor interaction, cAMP signaling pathway, and calcium signaling pathway might be the critical pathways upon which the capsule might act. The present study laid down a foundation to understand the molecular mechanisms of the XLGB capsule and also provided fundamental information for better improvement of the drug with the concept "less herbal materials for achieving equal treatment efficacy".
仙灵骨葆胶囊是一种传统中药,已获中国国家食品药品监督管理总局(CFDA)批准用于治疗骨关节炎(OA)和骨质疏松症(OP)。然而,作为一种成分复杂的胶囊,其治疗效果背后的分子机制尚未得到探索。
采用基于网络药理学的方法来探究仙灵骨葆活性成分靶点之间的复杂相互作用组。
该胶囊中的草药含有41种化合物,具有246个高分靶点,涵盖了美国食品药品监督管理局(FDA)批准的药物或正在进行临床试验的药物中的4个已知OA靶点(PTGS1、PTGS2、PTGER4和TNF)和6个已知OP靶点(AR、ESR1、PGR、PTGER2、TNFSF11和VDR)。这246个靶点的蛋白质-蛋白质相互作用(PPI)网络有6个关键模块。在这6个模块中,神经活性配体-受体相互作用、cAMP信号通路和钙信号通路是关键通路,它们都与关节软骨退变以及骨形成和吸收密切相关。
神经活性配体-受体相互作用、cAMP信号通路和钙信号通路可能是该胶囊发挥作用的关键通路。本研究为理解仙灵骨葆胶囊的分子机制奠定了基础,也为以“更少药材,同等疗效”理念更好地改进该药物提供了基础信息。