title: Chrysin, a PPAR-γ agonist improves myocardial injury in diabetic rats through inhibiting AGE-RAGE mediated oxidative stress and inflammation.
abstract: AGE-RAGE interaction mediated oxidative stress and inflammation is the key mechanism involved in the pathogenesis of cardiovascular disease in diabetes. Inhibition of AGE-RAGE axis by several PPAR-γ agonists has shown positive results in ameliorating cardio-metabolic disease conditions. Chrysin, a natural flavonoid has shown to possess PPAR-γ agonist activity along with antioxidant and anti-inflammatory effect. Therefore, the present study was designed to evaluate the effect of chrysin in isoproterenol-induced myocardial injury in diabetic rats. In male albino Wistar rats, diabetes was induced by single injection of streptozotocin (70 mg/kg, i.p.). After confirmation of the diabetes, rats were treated with vehicle (1.5 mL/kg, p.o.), chrysin (60 mg/kg, p.o.) or PPAR-γ antagonist GW9662 (1 mg/kg, i.p.) for 28 days. Simultaneously, on 27th and 28th day myocardial injury was induced by isoproterenol (85 mg/kg, s.c.). Chrysin significantly ameliorated cardiac dysfunction as reflected by improved MAP, ±LVdP/dtmax and LVEDP in diabetic rats. This improvement was associated with increased PPAR-γ expression and reduced RAGE expression in diabetic rats. Chrysin significantly decreased inflammation through inhibiting NF-κBp65/IKK-β expression and TNF-α level. Additionally, chrysin significantly reduced apoptosis as indicated by augmented Bcl-2 expression and decreased Bax and caspase-3 expressions. Furthermore, chrysin inhibited nitro-oxidative stress by normalizing the alteration in 8-OHdG, GSH, TBARS, NO and CAT levels and Nox4, MnSOD, eNOS and NT expressions. Co-administration of GW9662 significantly blunted the chrysin mediated cardioprotective effect as there was increase in oxidative stress, inflammation and apoptosis markers. Chrysin significantly ameliorated isoproterenol-induced myocardial injury in diabetic rats via PPAR-γ activation and inhibition of AGE-RAGE mediated oxidative stress and inflammation.
authors.affiliation: Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, 110029, India.
authors.forename: Neha
authors.initials: N
authors.lastname: Rani
authors.affiliation: Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, 110029, India.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Bharti
authors.affiliation: Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, 110029, India.
authors.forename: Jagriti
authors.initials: J
authors.lastname: Bhatia
authors.affiliation: Department of Anatomy, All India Institute of Medical Sciences, New Delhi, 110029, India.
authors.forename: T C
authors.initials: TC
authors.lastname: Nag
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, 110029, India.
authors.forename: Ruma
authors.initials: R
authors.lastname: Ray
authors.affiliation: Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, 110029, India. Electronic address: dsarya16@hotmail.com.
authors.forename: Dharamvir Singh
authors.initials: DS
authors.lastname: Arya
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D058065:Diabetic Cardiomyopathies / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005419:Flavonoids / Q000627:therapeutic use*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism
chemical_list: C000593873:Ager protein, mouse; D000975:Antioxidants; D002316:Cardiotonic Agents; D005419:Flavonoids; D017127:Glycation End Products, Advanced; D047495:PPAR gamma; D000067759:Receptor for Advanced Glycation End Products; C043561:chrysin
keywords: Chrysin; Diabetes; GW9662; Isoproterenol; Myocardial injury; PPAR-γ