{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T03:35:24Z","timestamp":1784086524720,"version":"3.55.0"},"reference-count":44,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["RS-2022-NR073471"],"award-info":[{"award-number":["RS-2022-NR073471"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Glucocorticoid therapy, using agents like dexamethasone (Dexa), often leads to muscle atrophy by increasing protein degradation via the ubiquitin\u2013proteasome system while suppressing protein synthesis. Stigmasterol, a phytosterol with known bioactivities, has an unexplored role in muscle atrophy. This study investigated stigmasterol\u2019s protective effects against Dexa-induced muscle atrophy and its impact on the FoxO3 and mTORC1 signaling pathways. Differentiated C2C12 myotubes were treated with Dexa (50 \u00b5M) \u00b1 stigmasterol (10 \u00b5M), and the morphology, viability, and protein levels in the FoxO3\/MuRF1\/MAFbx catabolic and mTOR\/p70S6K\/4E-BP1 anabolic signaling pathways were assessed. C57BL\/6 mice received Dexa (20 mg\/kg\/day i.p.) \u00b1 stigmasterol (3 mg\/kg\/day oral) for 21 days, and the body\/muscle mass, bone mineral density (BMD), fiber cross-sectional area (CSA), and muscle protein expression were measured. Stigmasterol (10 \u00b5M) was non-toxic and attenuated Dexa-induced reductions in myotube diameter and fusion in vitro, concurrent with suppressing Dexa-induced upregulation of FoxO3\/MuRF1\/MAFbx proteins and preventing the Dexa-induced dephosphorylation of mTOR\/p70S6K\/4E-BP1 proteins. In vivo, stigmasterol mitigated Dexa-induced losses in body weight, muscle mass, BMD, and fiber CSA. This protection was associated with attenuated upregulation of FoxO3 and MAFbx proteins in muscle tissue. Stigmasterol protected against Dexa-induced muscle atrophy in vitro and in vivo via modulation of the FoxO3\u2013MAFbx catabolic pathway. These findings suggest stigmasterol inhibits excessive glucocorticoid-induced muscle protein breakdown. It therefore warrants further investigation as a potential therapeutic agent for glucocorticoid myopathy.<\/jats:p>","DOI":"10.3390\/biom15111551","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T13:19:29Z","timestamp":1762348769000},"page":"1551","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Stigmasterol Protects Against Dexamethasone-Induced Muscle Atrophy by Modulating the FoxO3\u2013MuRF1\/MAFbx Signaling Pathway in C2C12 Myotubes and Mouse Skeletal Muscle"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8571-2722","authenticated-orcid":false,"given":"Young-Sool","family":"Hah","sequence":"first","affiliation":[{"name":"Department of Surgery, Institute of Medical Science, Gyeongsang National University College of Medicine and Gyeongsang National University Hospital, Jinju 52727, Republic of Korea"},{"name":"Biomedical Research Institute, Gyeongsang National University Hospital, Jinju 52727, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9749-7505","authenticated-orcid":false,"given":"Seung-Jun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Convergence Medical Sciences, Gyeongsang National University, Jinju 52725, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2297-6185","authenticated-orcid":false,"given":"Yeung-Ho","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Inha University Hospital, Inha University School of Medicine, Incheon 22332, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8798-7438","authenticated-orcid":false,"given":"Jeongyun","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Convergence Medical Sciences, Gyeongsang National University, Jinju 52725, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6394-942X","authenticated-orcid":false,"given":"Han-Gil","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Surgery, Institute of Medical Science, Gyeongsang National University College of Medicine and Gyeongsang National University Hospital, Jinju 52727, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1785-8500","authenticated-orcid":false,"given":"Young-Tae","family":"Ju","sequence":"additional","affiliation":[{"name":"Department of Surgery, Institute of Medical Science, Gyeongsang National University College of Medicine and Gyeongsang National University Hospital, Jinju 52727, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3575-4123","authenticated-orcid":false,"given":"Jun-Il","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Inha University Hospital, Inha University School of Medicine, Incheon 22332, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9267-9158","authenticated-orcid":false,"given":"Seung-Jin","family":"Kwag","sequence":"additional","affiliation":[{"name":"Department of Surgery, Institute of Medical Science, Gyeongsang National University College of Medicine and Gyeongsang National University Hospital, Jinju 52727, Republic of Korea"},{"name":"Biomedical Research Institute, Gyeongsang National University Hospital, Jinju 52727, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1093\/ageing\/afq034","article-title":"Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People","volume":"39","author":"Baeyens","year":"2010","journal-title":"Age Ageing"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1093\/ageing\/afy169","article-title":"Sarcopenia: Revised European consensus on definition and diagnosis","volume":"48","author":"Bahat","year":"2019","journal-title":"Age Ageing"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Go, H., Sung, N.J., Choi, J., Kim, L., and Park, E.J. 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