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Furthermore, the study investigated the associated molecular mechanisms. Cell viability was assessed using the MTT assay, and flow cytometry was employed to evaluate reactive oxygen species (ROS) production, alterations in mitochondrial membrane potential, and cytochrome c release. Lipid peroxidation levels, as well as the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH\u2010Px), and caspase enzymes, were quantified using commercially available assay kits. Bcl\u20102, Bax, heme oxygenase\u20101 (HO\u20101), and nuclear factor erythroid 2\u2010related factor 2 (Nrf2) expression was quantified through western blotting. Moreover, animal experiments were performed to assess BL\u2010induced retinal damage. The results revealed that irigenin protected against BL\u2010induced cytotoxicity and apoptosis in DA50062\u2010laden hARPE\u201019 cells. Furthermore, irigenin upregulated Bcl\u20102 expression and downregulated Bax expression in BL\u2010exposed DA50062\u2010laden hARPE\u201019 cells. Hence, irigenin prevented cytochrome c release and inhibited BL\u2010induced caspase\u20103 and caspase\u20109 activation in DA50062\u2010laden hARPE\u201019 cells. Irigenin also effectively inhibited lipid peroxidation and ROS production in BL\u2010exposed DA50062\u2010laden hARPE\u201019 cells. Notably, irigenin upregulated Nrf2 expression, which, in turn, upregulated the expression of several antioxidative defense system, such as SOD, CAT, and GSH\u2010Px, and HO\u20101 in BL\u2010exposed DA50062\u2010laden hARPE\u201019 cells. Animal studies showed that irigenin effectively protected against BL\u2010induced retinal damage, as indicated by the increased thickness of the outer and inner nuclear layers in irigenin\u2010treated groups compared to untreated controls. Taken together, the results suggest that irigenin inhibits the BL\u2010induced intrinsic apoptotic pathway by activating the Nrf2\u2010mediated antioxidative defense system.<\/jats:p>","DOI":"10.1002\/tox.24501","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T10:00:06Z","timestamp":1741687206000},"page":"1072-1086","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Irigenin Alleviates Blue Light\u2010Induced Retinal Damage by Upregulating Antioxidative Defense System via Nrf2 Pathway In\u00a0Vivo and In\u00a0Vitro"],"prefix":"10.1002","volume":"40","author":[{"given":"Kun\u2010Lin","family":"Yeh","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine, College of Veterinary Medicine National Chung Hsing University  Taichung 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