title: Anti-hyperlipidemic and anti-peroxidative role of pterostilbene via Nrf2 signaling in experimental diabetes.
abstract: Nuclear factor erythroid 2-related factor (Nrf2), a key transcription factor triggers the expression of antioxidant and detoxification genes thereby providing cellular protective functions against oxidative stress-mediated disorders. Recent research has identified that pharmacological activation of Nrf2 also regulates the largest cluster of genes associated with lipid metabolism. With this background, this paper highlights the anti-hyperlipidemic and anti-peroxidative role of pterostilbene (PTS), an Nrf2 activator, in streptozotocin (STZ)-induced diabetic model. PTS administration to diabetic mice for 5 weeks significantly regulated blood glucose levels through the elevation of insulin secretion. The circulatory and liver lipid profiles of total cholesterol (TC), triglycerides (TG) and non-esterified fatty acids (NEFA) were maintained to normal levels upon PTS treatment. Moreover, PTS administration also normalized the circulatory levels of very low-, low- and high density lipoprotein cholesterols (VLDL-, LDL-, HDL-C) and also reduced lipid peroxidation in STZ-induced diabetic mice. In addition, Nrf2 and its downstream targets, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) enzyme activities and glutathione (GSH) levels were significantly elevated in liver tissues of diabetic mice upon PTS administration. Further, H&E staining of diabetic mouse liver showed collapse in hepatic microvesicles due to altered lipid metabolism. Both structural and functional alterations were attenuated by PTS indicating its role in diabetic dyslipidemia through Nrf2-mediated mechanism that could be considered as a promising therapeutic agent.
authors.affiliation: SRM Research Institute, SRM University, Kattankulathur 603203, Tamilnadu, India.
authors.forename: Elango
authors.initials: E
authors.lastname: Bhakkiyalakshmi
authors.affiliation: SRM Research Institute, SRM University, Kattankulathur 603203, Tamilnadu, India.
authors.forename: Dornadula
authors.initials: D
authors.lastname: Sireesh
authors.affiliation: King Institute of Preventive Medicine and Research, Guindy, Chennai 600032, Tamilnadu, India.
authors.forename: Murugesan
authors.initials: M
authors.lastname: Sakthivadivel
authors.affiliation: King Institute of Preventive Medicine and Research, Guindy, Chennai 600032, Tamilnadu, India.
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Sivasubramanian
authors.affiliation: King Institute of Preventive Medicine and Research, Guindy, Chennai 600032, Tamilnadu, India.
authors.forename: Palani
authors.initials: P
authors.lastname: Gunasekaran
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; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects*; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D008074:Lipoproteins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D013267:Stilbenes; C107773:pterostilbene
keywords: Diabetes; Dyslipidemia; Lipids; Nrf2; Pterostilbene; Streptozotocin