Exploring the Pharmacological Mechanisms of Xiaochaihu Tang in Treating Postmenopausal Osteoporosis: A Study Based on Network Pharmacology and Experimental Validation

ABSTRACT Osteoporosis (OP) is characterized by reduced bone mass and deteriorated bone structure, leading to an increased risk of fractures. Xiao Chai Hu Tang (XCHT), a traditional Chinese medicine, has shown promise in alleviating OP, but its underlying mechanisms remain unclear. This study aimed to identify the active compounds in XCHT, screen core targets related to postmenopausal osteoporosis (PMOP), and explore its therapeutic mechanisms. Active compounds in XCHT were identified using LC‐Q‐MS/MS, and PMOP‐related targets were screened via protein–protein interaction (PPI) network analysis. Gene Ontology (GO) and KEGG pathway analyses were conducted to explore core signaling pathways, while in vivo validation was performed using ovariectomized rats. Network pharmacology revealed 278 XCHT targets, with 145 related to PMOP. PPI analysis identified 20 core targets. GO and KEGG analyses suggested that XCHT may regulate gene expression, apoptosis, and inflammation via the MAPK signaling pathway. LC–MS identified 49 active compounds. Animal studies confirmed that XCHT mediates MAPK signaling to treat OP. Overall, the findings suggest that XCHT improves PMOP by regulating apoptosis and inflammation through the MAPK pathway, promoting osteoblast formation and reducing osteoblast apoptosis, providing valuable insights into its potential therapeutic role in PMOP.