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Chrysin, a PPAR-γ agonist improves myocardial injury in diabetic rats through inhibiting AGE-RAGE mediated oxidative stress and inflammation.
Chem Biol Interact. 2016 Apr 25; 250:59-67.CB

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+Show Affiliations

Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, 110029, India.Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, 110029, India.Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, 110029, India.Department of Anatomy, All India Institute of Medical Sciences, New Delhi, 110029, India.Department of Pathology, All India Institute of Medical Sciences, New Delhi, 110029, India.Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, 110029, India. Electronic address: dsarya16@hotmail.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26972669

Citation

Rani, Neha, et al. "Chrysin, a PPAR-γ Agonist Improves Myocardial Injury in Diabetic Rats Through Inhibiting AGE-RAGE Mediated Oxidative Stress and Inflammation." Chemico-biological Interactions, vol. 250, 2016, pp. 59-67.
Rani N, Bharti S, Bhatia J, et al. Chrysin, a PPAR-γ agonist improves myocardial injury in diabetic rats through inhibiting AGE-RAGE mediated oxidative stress and inflammation. Chem Biol Interact. 2016;250:59-67.
Rani, N., Bharti, S., Bhatia, J., Nag, T. C., Ray, R., & Arya, D. S. (2016). Chrysin, a PPAR-γ agonist improves myocardial injury in diabetic rats through inhibiting AGE-RAGE mediated oxidative stress and inflammation. Chemico-biological Interactions, 250, 59-67. https://doi.org/10.1016/j.cbi.2016.03.015
Rani N, et al. Chrysin, a PPAR-γ Agonist Improves Myocardial Injury in Diabetic Rats Through Inhibiting AGE-RAGE Mediated Oxidative Stress and Inflammation. Chem Biol Interact. 2016 Apr 25;250:59-67. PubMed PMID: 26972669.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chrysin, a PPAR-γ agonist improves myocardial injury in diabetic rats through inhibiting AGE-RAGE mediated oxidative stress and inflammation. AU - Rani,Neha, AU - Bharti,Saurabh, AU - Bhatia,Jagriti, AU - Nag,T C, AU - Ray,Ruma, AU - Arya,Dharamvir Singh, Y1 - 2016/03/10/ PY - 2015/10/15/received PY - 2016/02/13/revised PY - 2016/03/08/accepted PY - 2016/3/15/entrez PY - 2016/3/15/pubmed PY - 2016/8/18/medline KW - Chrysin KW - Diabetes KW - GW9662 KW - Isoproterenol KW - Myocardial injury KW - PPAR-γ SP - 59 EP - 67 JF - Chemico-biological interactions JO - Chem. Biol. Interact. VL - 250 N2 - 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. SN - 1872-7786 UR - https://www.unboundmedicine.com/medline/citation/26972669/Chrysin_a_PPAR_γ_agonist_improves_myocardial_injury_in_diabetic_rats_through_inhibiting_AGE_RAGE_mediated_oxidative_stress_and_inflammation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0009-2797(16)30078-3 DB - PRIME DP - Unbound Medicine ER -