A network pharmacological study to unveil the mechanisms of xianlinggubao capsule in the treatment of osteoarthritis and osteoporosis.

Introduction: 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. Material and methods: A network pharmacology-based approach was conducted to explore the complex interactome among the targets of the XLGB active compounds. Results: 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. Conclusions: 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".