Elucidating Wenshen Xuanbi Decoction's Anti‐Osteoporotic Mechanisms via Integrated Multiomics Analysis

This study aimed to systematically investigate the active components and therapeutic mechanisms of Wenshen Xuanbi Decoction (WSXBT) against primary osteoporosis (POP) using an integrated multi‐omics approach. HPLC‐Q‐TOF‐MS/MS analysis identified 28 chemical constituents in WSXBT. Through network pharmacology, transcriptomic profiling (GSE35958), single‐cell RNA sequencing (GSE147287), and weighted gene co‐expression network analysis (WGCNA), we identified 15 core targets of WSXBT against POP, with CTNNB1 and AKT1 emerging as the top candidates. Enrichment analyses revealed that these targets are involved in key biological processes, such as cellular senescence, osteoclast differentiation, Wnt signaling, and the PI3K‐Akt pathway. Molecular docking and dynamics simulations confirmed stable binding between key WSXBT components (e.g., glycyrrhizic acid) and the core targets AKT1 and CTNNB1. Our findings suggest that WSXBT exerts its anti‐osteoporotic effects by modulating the PI3K‐AKT and Wnt signaling pathways, thereby promoting osteogenesis and inhibiting osteoclastogenesis. This study provides a scientific basis for the clinical application of WSXBT and advances the understanding of multi‐target mechanisms underlying traditional Chinese medicine compound actions.