{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T05:01:14Z","timestamp":1775624474666,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82400874"],"award-info":[{"award-number":["82400874"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004479","name":"Natural Science Foundation of Jiangxi Province","doi-asserted-by":"publisher","award":["20242BAB20362"],"award-info":[{"award-number":["20242BAB20362"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Postmenopausal osteoporosis (PMOP) results from estrogen deficiency, oxidative stress, and impaired bone formation, yet effective treatments remain limited. In this study, we identify the natural isoflavone ononin as a potent antiosteoporotic compound and uncover its mechanism through activation of aldehyde dehydrogenase 2 (ALDH2). Using an ovariectomized (OVX) mouse model and bone marrow\u2010derived mesenchymal stem cells (BMSCs), we evaluated the in\u00a0vivo and in\u00a0vitro effects of ononin. An integrated approach combining network pharmacology, molecular docking, enzymatic assays, and ALDH2 knockout (\n                    <jats:italic>Aldh2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) models was employed to verify its molecular target. Ononin significantly alleviated OVX\u2010induced trabecular bone loss and promoted osteogenic differentiation of BMSCs in a dose\u2010dependent manner. Mechanistically, network pharmacology and docking analyses identified ALDH2 as the primary target. Enzymatic assays confirmed that ononin robustly enhances ALDH2 activity, reduces reactive oxygen species, lowers 4\u2010hydroxynonenal and malondialdehyde levels, and maintains mitochondrial integrity. These beneficial effects were largely abolished in\n                    <jats:italic>Aldh2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, confirming the dependence on ALDH2 activation. Collectively, these findings demonstrate that ononin protects against PMOP by promoting ALDH2\u2010mediated osteogenesis and restoring redox balance, highlighting its potential as a natural therapeutic agent for postmenopausal osteoporosis.\n                  <\/jats:p>","DOI":"10.1002\/ptr.70258","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T08:40:02Z","timestamp":1770626402000},"page":"2098-2109","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ononin Mitigates Estrogen Deficiency\u2010Induced Osteoporosis Through Activation of\n                    <scp>ALDH2<\/scp>\n                    in Mice"],"prefix":"10.1002","volume":"40","author":[{"given":"Mingchuan","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Medicine The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University  Nanchang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong","family":"Ruan","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University  Nanchang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wentao","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Trauma Emergency Center Ganzhou People's Hospital  Ganzhou China"},{"name":"Ganzhou City Key Laboratory of Bone Metabolism  Ganzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haimin","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University  Nanchang China"},{"name":"The Second Clinical Medical College, Jiangxi Medical College, Nanchang University  Nanchang 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