{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:14:38Z","timestamp":1785413678184,"version":"3.56.0"},"reference-count":50,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82003460"],"award-info":[{"award-number":["82003460"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82103841"],"award-info":[{"award-number":["82103841"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82003460"],"award-info":[{"award-number":["82003460"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82103841"],"award-info":[{"award-number":["82103841"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002767","name":"the Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2025JJ50561"],"award-info":[{"award-number":["2025JJ50561"]}],"id":[{"id":"10.13039\/501100002767","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002767","name":"the Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2021JJ40807"],"award-info":[{"award-number":["2021JJ40807"]}],"id":[{"id":"10.13039\/501100002767","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002767","name":"the Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2024JJ6266"],"award-info":[{"award-number":["2024JJ6266"]}],"id":[{"id":"10.13039\/501100002767","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010451","name":"the Health Research Project of the Hunan Provincial Health Commission","doi-asserted-by":"publisher","award":["W20243298"],"award-info":[{"award-number":["W20243298"]}],"id":[{"id":"10.13039\/501100010451","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Bisphenol F (BPF), a widely used bisphenol A substitute and emerging endocrine disruptor, has been implicated in bone loss; however, its underlying mechanisms remain unclear. Curcumin (CUR) has shown beneficial effects on bone metabolism, but its protective role against BPF-induced osteogenic impairment requires further validation. This study investigated the involvement of the PI3K\/AKT signaling pathway in BPF-induced osteoporosis and osteogenic dysfunction, and whether CUR could alleviate these effects through modulation of this pathway. Methods: Network toxicology, network pharmacology, and molecular docking were first used to predict potential targets and signaling pathways. A rat model of BPF-induced osteoporosis and a BPF-treated MC3T3-E1 osteogenic impairment model were then established to evaluate the effects of CUR. Bone mineral density, trabecular microarchitecture, serum bone metabolism markers, and osteogenic protein expression were assessed in vivo. In vitro, alkaline phosphatase activity, mineralization, and key signaling proteins were measured. The PI3K\/AKT inhibitor LY294002 was used to verify pathway involvement. Results: Computational analyses suggested that BPF and CUR were closely associated with the PI3K\/AKT pathway. Experimentally, BPF reduced bone mass, disrupted trabecular structure, and suppressed osteogenic differentiation, accompanied by downregulation of osteogenic markers and PI3K\/AKT signaling. Notably, BPF reduced femoral BMD by 10.8%, whereas CUR restored approximately 43.5% of the BPF-induced loss. CUR significantly reversed these effects, whereas LY294002 abolished the protective actions of CUR. Conclusions: BPF may impair bone formation and promote osteoporosis by suppressing PI3K\/AKT signaling, while CUR alleviates these effects through pathway activation. These findings provide mechanistic evidence supporting CUR as a potential intervention against BPF-related bone toxicity.<\/jats:p>","DOI":"10.3390\/nu18142335","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:55:59Z","timestamp":1784249759000},"page":"2335","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Curcumin Attenuates Bisphenol F-Induced Osteoporosis and Osteogenic Dysfunction via PI3K\/AKT Pathway Activation"],"prefix":"10.3390","volume":"18","author":[{"given":"Yue","family":"Su","sequence":"first","affiliation":[{"name":"Xiangya School of Public Health, Central South University, Changsha 410078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Li","sequence":"additional","affiliation":[{"name":"Xiangya School of Public Health, Central South University, Changsha 410078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Xiangya School of Public Health, Central South University, Changsha 410078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Liang","sequence":"additional","affiliation":[{"name":"Xiangya School of Public Health, Central South University, Changsha 410078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiongfei","family":"Hu","sequence":"additional","affiliation":[{"name":"Hunan Prevention and Treatment Institute of Occupational Diseases, Changsha 410007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7899-4154","authenticated-orcid":false,"given":"Gang","family":"Luo","sequence":"additional","affiliation":[{"name":"Xiangya School of Public Health, Central South University, Changsha 410078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuhong","family":"Yang","sequence":"additional","affiliation":[{"name":"Hunan Prevention and Treatment Institute of Occupational Diseases, Changsha 410007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4170-2044","authenticated-orcid":false,"given":"Qiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Hunan Provincial Center for Disease Control and Prevention (Hunan Academy of Preventive Medicine), Changsha 410153, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4940-4423","authenticated-orcid":false,"given":"Lin","family":"Xiao","sequence":"additional","affiliation":[{"name":"Xiangya School of Public Health, Central South University, Changsha 410078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1007\/BF01622200","article-title":"Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: Synopsis of a WHO report","volume":"4","author":"Kanis","year":"1994","journal-title":"WHO Study Group. 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