title: Antiaging Effect of Metformin on Brain in Naturally Aged and Accelerated Senescence Model of Rat.
abstract: Metformin, a biguanide, is a widely used antidiabetic drug, which inhibits gluconeogenesis and is used to treat hyperglycemia in type 2 diabetes. Through activation of AMPK (AMP-activated protein kinase) pathway, metformin also mimics caloric restriction health benefits. Aging causes substantial molecular to morphological changes in brain, the brain cells being more susceptible toward oxidative stress mediated damages due to the presence of high lipid content and higher oxygen consumption. Wistar rats (naturally aged and d-galactose induced rat model) were supplemented with metformin (300 mg/kg b.w. orally) for 6 weeks. The biomarkers of oxidative stress such as antioxidant capacity (ferric reducing antioxidant potential [FRAP]), malondialdehyde (MDA), reduced glutathione (GSH), protein carbonyl (PCO), reactive oxygen species (ROS), acetylcholinesterase (AChE) activity, and nitric oxide (NO) were measured in brain tissues of control and experimental groups. The results indicate that metformin treatment augmented the levels of FRAP and GSH in naturally aged, and d-gal induced aging model groups compared to the respective controls. In contrast, metformin treated groups exhibited significant reduction in MDA, PCO, ROS, and NO levels and a significant increase in AChE activity in induced aging rats. The administration of d-galactose upregulated the expression of sirtuin-2, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) and downregulated the expression of Beclin-1. Metformin supplementation downregulated the d-galactose induced expressions of sirtuin-2, IL-6, and TNF-α expression, whereas upregulated the Beclin-1 expression. Our data confirm that metformin restores the antioxidant status and improves healthy brain aging through the activation of autophagy and reduction in inflammation.
authors.affiliation: Department of Biochemistry, University of Allahabad , Allahabad, India .
authors.forename: Geetika
authors.initials: G
authors.lastname: Garg
authors.affiliation: Department of Biochemistry, University of Allahabad , Allahabad, India .
authors.forename: Sandeep
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Biochemistry, University of Allahabad , Allahabad, India .
authors.forename: Abhishek Kumar
authors.initials: AK
authors.lastname: Singh
authors.affiliation: Department of Biochemistry, University of Allahabad , Allahabad, India .
authors.forename: Syed Ibrahim
authors.initials: SI
authors.lastname: Rizvi
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000375:Aging / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D007501:Iron / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology; D050050:Protein Carbonylation / Q000187:drug effects; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D020011:Protective Agents; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D008687:Metformin; D007501:Iron; D000110:Acetylcholinesterase
keywords: aging; autophagy; brain; d-galactose; metformin