title: Morin activates the Nrf2-ARE pathway and reduces oxidative stress-induced DNA damage in pancreatic beta cells.
abstract: Oxidative stress is an important factor contributing to the pathogenesis of diabetes and its complications. In our earlier study, we demonstrated the antidiabetic efficacy of morin by regulating key enzymes of carbohydrate metabolism in diabetic rats. The present study was designed to assess the antigenotoxic potential of morin in pancreatic β-cells, using the COMET assay. To explore its potential mechanisms of action, three genotoxic agents, H2O2which induces DNA damage by the generation of reactive oxygen species, streptozotocin (STZ) by RNS and Methyl methanesulfonate (MMS) by DNA alkylation was used. We found that STZ and H2O2- induced genotoxicity was dose dependently reduced by morin as assessed by DNA tail length, tail moment, DNA content and olive moment. Since the protective property was found to be specific against oxidative DNA damage, we explored the molecular mechanism underlying morin-induced Nuclear factor erythroid 2-related factor 2 (Nrf2) activation in pancreatic β-cells as assessed by ARE-driven downstream target genes with Luciferase reporter assay. In addition, morin inhibited intracellular free radical generation as assessed by using DCFDA and increased the intra cellular antioxidants viz, superoxide dismutase and catalase in INS-1E cells. In addition, morin attenuated glucose-stimulated insulin secretion following exposure to oxidative stress by STZ (P<0.05). Collectively, our data provide evidence that morin protects pancreatic β-cells against oxidative stress-induced DNA damage by activating the Nrf2 signaling pathway.
authors.affiliation: Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603203, Tamilnadu, India.
authors.forename: Pachamuthu
authors.initials: P
authors.lastname: Vanitha
authors.affiliation: Department of Biotechnology, Anna University-BIT campus, Tiruchirappalli 620024, Tamilnadu, India.
authors.forename: Sankareswaran
authors.initials: S
authors.lastname: Senthilkumar
authors.affiliation: SRM Research Institute, SRM University, Kattankulathur 603203, Tamilnadu, India.
authors.forename: Sireesh
authors.initials: S
authors.lastname: Dornadula
authors.affiliation: SRM Research Institute, SRM University, Kattankulathur 603203, Tamilnadu, India.
authors.forename: Sundaramurthy
authors.initials: S
authors.lastname: Anandhakumar
authors.affiliation: Department of Biotechnology, Anna University-BIT campus, Tiruchirappalli 620024, Tamilnadu, India.
authors.forename: Palanisamy
authors.initials: P
authors.lastname: Rajaguru
authors.affiliation: SRM Research Institute, SRM University, Kattankulathur 603203, Tamilnadu, India. Electronic address: ramkumar.km@res.srmuniv.ac.in.
authors.forename: Kunka Mohanram
authors.initials: KM
authors.lastname: Ramkumar
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D045744:Cell Line, Tumor; D004249:DNA Damage; D005419:Flavonoids / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008698:Mesylates / Q000494:pharmacology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D020218:Response Elements / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D047309:Flavones
chemical_list: D000975:Antioxidants; D005419:Flavonoids; D006861:Hydrogen Peroxide; D008698:Mesylates; D051267:NF-E2-Related Factor 2; C045880:methanesulfonic acid; C008548:morin; D047309:Flavones
keywords: Antioxidant; Beta cells; Comet assay; DNA damage; Diabetes; Morin