title: Prevention of cardiac dysfunction, kidney fibrosis and lipid metabolic alterations in l-NAME hypertensive rats by sinapic acid--Role of HMG-CoA reductase.
abstract: The present study was designed to evaluate the effect of sinapic acid, a bioactive phenolic acid on high blood pressure associated cardiac dysfunction, kidney fibrosis and lipid alterations in N(ω)-nitro-l-arginine methyl ester hydrochloride (l-NAME) induced hypertensive rats. Sinapic acid was administered to rats orally at a dosage of 40 mg/kg everyday for a period of 4 weeks. Sinapic acid treatment significantly decreased mean arterial pressure, left ventricular end diastolic pressure, organ weights (liver and kidney), lipid peroxidation products in tissues (liver and kidney), activities of hepatic marker enzymes and the levels of renal function markers in serum of l-NAME rats. Sinapic acid treatment also significantly increased the level of plasma nitric oxide metabolites, and enzymatic and non-enzymatic antioxidants in tissues of l-NAME rats. Tissue damage was assessed by histopathological examination. Alterations in plasma angiotensin-converting enzyme activity, level of plasma lipoproteins and tissue lipids were corrected by sinapic acid treatment in l-NAME rats. Sinapic acid treatment significantly decreased the activity of 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase in plasma and liver, whereas the activity of lecithin cholesterol acyl transferase was significantly increased in the plasma of hypertensive rats. Docking result showed the interaction between sinapic acid and HMG-CoA reductase. Sinapic acid has shown best ligand binding energy of -5.5 kcal/M. Moreover, in chick embryo model, sinapic acid improved vessel density on chorioallantoic membrane. These results of the present study concludes that sinapic acid acts as a protective agent against hypertension associated cardiac dysfunction, kidney fibrosis and lipid alterations.
authors.affiliation: Cardiovascular Biology Lab, Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamil Nadu, India.
authors.forename: Thangarasu
authors.initials: T
authors.lastname: Silambarasan
authors.affiliation: Cardiovascular Biology Lab, Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamil Nadu, India; Vascular Biology Lab, AU-KBC Research Centre, Anna University, Chennai, Tamil Nadu, India.
authors.forename: Jeganathan
authors.initials: J
authors.lastname: Manivannan
authors.affiliation: Cardiovascular Biology Lab, Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamil Nadu, India. Electronic address: drrajaau@gmail.com.
authors.forename: Boobalan
authors.initials: B
authors.lastname: Raja
authors.affiliation: Vascular Biology Lab, AU-KBC Research Centre, Anna University, Chennai, Tamil Nadu, India.
authors.forename: Suvro
authors.initials: S
authors.lastname: Chatterjee
mesh_terms: D000214:Acyl Coenzyme A / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D003373:Coumaric Acids / Q000378:metabolism / Q000494:pharmacology*; D005355:Fibrosis; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology*; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D062105:Molecular Docking Simulation; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D011487:Protein Conformation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000214:Acyl Coenzyme A; D000975:Antioxidants; D003373:Coumaric Acids; D008074:Lipoproteins; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D009569:Nitric Oxide; C073734:sinapinic acid; D019331:NG-Nitroarginine Methyl Ester
keywords: Cardiac dysfunction; Dyslipidemia; Kidney fibrosis; Oxidative stress; Sinapic acid