{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:50:48Z","timestamp":1792173048494,"version":"4.4.0"},"reference-count":59,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T00:00:00Z","timestamp":1791676800000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Berberine, an alkaloid with broad bioactive properties, exerts its pleiotropic effects by modulating SIRT3, a mitochondrial NAD\n                    <jats:sup>+<\/jats:sup>\n                    \u2010dependent deacetylase. This review examines the dual role of SIRT3 as a target of berberine in the management of various disorders while also addressing its associated toxicological profiles. The antihyperglycemic effects of berberine are mediated through SIRT3 inhibition, which promotes hyperacetylation of complex I subunits, degradation of MPC1, an increased AMP\/ATP ratio, AMPK activation, and suppression of PEPCK1, collectively resulting in the inhibition of gluconeogenesis. In contrast, the hypolipidemic, cardioprotective, and hepatoprotective effects of berberine are associated with SIRT3 activation, which facilitating adipose tissue remodeling, enhancing \u03b2\u2010oxidation in NAFLD, promoting lipophagy in diabetic cardiomyopathy, and mitigates doxorubicin\u2010induced cardiotoxicity. Furthermore, berberine exhibits antitumor duality, exerting contrasting effects in colorectal cancer and hepatoma models, and demonstrates versatile mitochondrial metabolic reprogramming in polycystic ovarian syndrome. Notably, ocular toxicity associated with berberine has been linked to SIRT3 inhibition in photoreceptors cells. Overall, the therapeutic versatility of berberine is fundamentally associated with its context\u2010dependent modulation of SIRT3, positioning it as a promising mitochondrial epigenetics modulator for conditions such as metabolic syndrome, NAFLD, and DCM. However, its therapeutic application must be carefully balanced against organ\u2010specific toxicity risks.\n                  <\/jats:p>","DOI":"10.1002\/jbt.71126","type":"journal-article","created":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T13:50:22Z","timestamp":1791726622000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["SIRT3\u2010Dependent Actions of Berberine: From Molecular Therapies to Toxicity"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5919-9750","authenticated-orcid":false,"given":"Dareuosh","family":"Shackebaei","sequence":"first","affiliation":[{"name":"Medical Biology Research Center, Health Technology Institute Kermanshah University of Medical Sciences Kermanshah Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8022-8387","authenticated-orcid":false,"given":"Seyed Shahram","family":"Miraghaee","sequence":"additional","affiliation":[{"name":"Medical Biology Research Center, Health Technology Institute Kermanshah University of Medical Sciences Kermanshah Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1332-3311","authenticated-orcid":false,"given":"Faegheh","family":"Farhadi","sequence":"additional","affiliation":[{"name":"Herbal and Traditional Medicines Research Center, Institute of Pharmaceutical Sciences Kerman University of Medical Sciences Kerman Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9941-0357","authenticated-orcid":false,"given":"Abolfazl","family":"Akbarzadeh","sequence":"additional","affiliation":[{"name":"Razi Drug Research Center Iran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0552-8766","authenticated-orcid":false,"given":"Fatemeh","family":"Yarmohammadi","sequence":"additional","affiliation":[{"name":"Razi Drug Research Center Iran University of Medical Sciences Tehran 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