{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T14:45:41Z","timestamp":1792421141494,"version":"4.5.0"},"reference-count":57,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Prince of Songkla University","award":["22105"],"award-info":[{"award-number":["22105"]}]},{"name":"Prince of Songkla University","award":["SCI6202039S"],"award-info":[{"award-number":["SCI6202039S"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diabetes-related osteoporosis has been known to be a consequence of oxidative stress caused by excessive reactive oxygen species (ROS) production in the tissues. Despite the increase in the number of individuals with diabetes-related osteoporosis year on year, there is still no effective drug that does not induce adverse side effects. Glabridin, which exerts hypoglycemic effects and possesses antioxidant properties, may have beneficial effects in the treatment of diabetes-related osteoporosis. In this study, we aimed to investigate the preventive effects of glabridin in counteracting oxidative stress-induced bone loss and its underlying mechanisms. A diabetic rat model was established by a single intraperitoneal injection of streptozotocin into male Wistar rats. The diabetic rats were orally gavaged daily with glabridin or glyburide for 8 weeks. The presence of diabetes significantly decreased the rats\u2019 tibia length, bone thickness, epiphyseal plate length, and collagen deposition compared to the control rats; in comparison, treatment with glabridin for 8 weeks significantly reversed these effects. In our in vitro study, the treatment of MC3T3-E1 preosteoblasts with glabridin up to 7.5 \u00b5M for 48 h showed no cytotoxic effect. However, pretreatment with glabridin significantly prevented oxidative stress-induced inhibition of cell proliferation. In addition, glabridin significantly diminished ROS production, restored antioxidant enzyme activity, and mitigated cellular apoptosis. These effects occurred by stimulating the phosphorylation of Akt, GSK-3\u03b2, and P65 NF-\u0138B proteins. The above results show that glabridin alleviated oxidative stress-induced bone loss and osteoblast cell apoptosis by modulating the expression of the Akt\/NF-\u0138B and Akt\/GSK-3\u03b2 pathways.<\/jats:p>","DOI":"10.3390\/ijms26072949","type":"journal-article","created":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T12:01:50Z","timestamp":1742817710000},"page":"2949","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Glabridin Alleviates Oxidative Stress-Induced Osteoporosis by Targeting the Akt\/NF-\u0138B and Akt\/GSK-3\u03b2 Pathways"],"prefix":"10.3390","volume":"26","author":[{"given":"Chittipong","family":"Tipbunjong","sequence":"first","affiliation":[{"name":"Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wipapan","family":"Khimmaktong","sequence":"additional","affiliation":[{"name":"Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanaporn","family":"Hengpratom","sequence":"additional","affiliation":[{"name":"Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanvarin","family":"Thitiphatphuvanon","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Kasetsart University, Bangkok 10900, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chumpol","family":"Pholpramool","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piyaporn","family":"Surinlert","sequence":"additional","affiliation":[{"name":"Thammasat University Research Unit in Synthesis and Applications of Graphene, Thammasat University, Pathum-Thani 12120, Thailand"},{"name":"Chulabhorn International College of Medicine, Thammasat University, Pathum-Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ishtaya, G.A., Anabtawi, Y.M., Zyoud, S.E.H., and Sweileh, W.M. 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