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HPLC\u2010Q\u2010TOF\u2010MS\/MS analysis identified 28 chemical constituents in WSXBT. Through network pharmacology, transcriptomic profiling (GSE35958), single\u2010cell RNA sequencing (GSE147287), and weighted gene co\u2010expression 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\u2010Akt 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\u2010osteoporotic effects by modulating the PI3K\u2010AKT 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\u2010target mechanisms underlying traditional Chinese medicine compound actions.<\/jats:p>","DOI":"10.1002\/bmc.70273","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:45:11Z","timestamp":1764549911000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Elucidating Wenshen Xuanbi Decoction's Anti\u2010Osteoporotic Mechanisms via Integrated Multiomics Analysis"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0975-0425","authenticated-orcid":false,"given":"Hu","family":"Jianbo","sequence":"first","affiliation":[{"name":"Department of Orthopedics and Traumatology Suqian Affiliated Hospital of Nanjing University of Chinese Medicine  Suqian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3742-7560","authenticated-orcid":false,"given":"Hu","family":"Yuan","sequence":"additional","affiliation":[{"name":"Suqian Hospital, Nanjing Drum Tower Hospital Group  Suqian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9475-3518","authenticated-orcid":false,"given":"Sun","family":"Jiahao","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Jiangsu Province Hospital of Chinese Medicine Affiliated Hospital of Nanjing University of Chinese Medicine  Nanjing Jiangsu Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5162-695X","authenticated-orcid":false,"given":"Shen","family":"Jirong","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Jiangsu Province Hospital of Chinese Medicine Affiliated Hospital of Nanjing University of Chinese Medicine  Nanjing Jiangsu Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,30]]},"reference":[{"key":"e_1_2_14_2_1","article-title":"Transparency in the Reporting of Artificial INtelligence\u2014The TITAN Guideline","volume":"10","author":"Agha R. 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