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Bazi Bushen, a Chinese patented medicine, has been demonstrated to be effective in attenuating OP, but the pharmacological mechanism remains predominantly unclear. In this study, the senescence\u2010accelerated mouse prone 6 (SAMP6) model was used to explore bone homeostasis and treated intragastrically for 9\u2009weeks with Bazi Bushen. In\u00a0vivo experiments showed that Bazi Bushen treatment not only upregulated the levels of bone mineral density and bone mineral content but also increased the content of RUNX2 and OSX. Furthermore, the primary culture of bone mesenchymal stem cells (BMSCs) in SAMP6 mice was used to verify the effects of Bazi Bushen on the balance of differentiation between osteoblasts and adipocytes, as well as ROS and aging levels. Finally, the pharmacological mechanism of Bazi Bushen in attenuating OP was investigated through network pharmacology and experimental verification, and we found that Bazi Bushen could significantly orchestrate bone homeostasis and attenuate the progression of OP by stimulating PI3K\u2010Akt and inhibiting apoptosis. In summary, our work sheds light on the first evidence that Bazi Bushen attenuates OP by regulating PI3K\u2010AKT and apoptosis pathways to orchestrate bone homeostasis.<\/jats:p>","DOI":"10.1111\/jcmm.70161","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T10:21:52Z","timestamp":1730197312000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Bazi Bushen attenuates osteoporosis in <scp>SAMP6<\/scp> mice by regulating <scp>PI3K<\/scp>\u2010<scp>AKT<\/scp> and apoptosis pathways"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9705-8924","authenticated-orcid":false,"given":"Zhe","family":"Xu","sequence":"first","affiliation":[{"name":"School of Integrative Medicine Tianjin University of Traditional Chinese Medicine  Tianjin P.R. China"},{"name":"Graduate School Tianjin University of Traditional Chinese Medicine  Tianjin P.R. 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