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Hexahydrocurcumin ameliorates hypertensive and vascular remodeling in L-NAME-induced rats.

Abstract
Hexahydrocurcumin (HHC), a major metabolite of curcumin, possesses several biological activities such as antioxidant, anti-inflammation, and cardioprotective properties. This study aimed to investigate the effect of HHC on high blood pressure, vascular dysfunction, and remodeling induced by N-nitro L-arginine methyl ester (L-NAME) in rats. Male Wistar rats (200-250 g) received L-NAME (40 mg/kg) via drinking water for seven weeks. HHC at doses of 20, 40 or 80 mg/kg or enalapril 10 mg/kg was orally administered for the last three weeks. Blood pressure was measured weekly. Rats induced with L-NAME showed the development of hypertension, vascular dysfunction, and remodeling as demonstrated by an increase in wall thickness, cross-sectional area, and collagen deposition in the aorta. The overexpression of nuclear factor kappa B (NF-кB), vascular cell adhesion molecule 1 (VCAM1), intercellular adhesion molecule 1 (ICAM1), tumor necrosis factor-alpha (TNF-α), phosphorylated-extracellular-regulated kinase 1/2 (p-ERK1/2), phosphorylated-c-Jun N-terminal kinases (p-JNK), phosphorylated-mitogen activated protein kinase p38 (p-p38), transforming growth factor-beta 1 (TGF-β1), matrix metalloproteinase-9 (MMP-9) and collagen type 1 was observed in L-NAME-induced hypertensive rats. Increased oxidative stress markers, decreased plasma nitric oxide (NO) levels and the down-regulation of endothelial nitric oxide synthase (eNOS) expression in aortic tissues were also found in L-NAME-induced rats. Moreover, L-NAME-induced rats showed enhanced synthetic protein expression in aortic tissues. These alterations were suppressed in hypertensive rats treated with HHC or enalapril. The present study shows that HHC exhibited antihypertensive effects by improving vascular function and ameliorated the development of vascular remodeling. The responsible mechanism may involve antioxidant and anti-inflammation potential.
AuthorsLuckika Panthiya, Jiraporn Tocharus, Amnart Onsa-Ard, Waraluck Chaichompoo, Apichart Suksamrarn, Chainarong Tocharus
JournalBiochimica et biophysica acta. Molecular basis of disease (Biochim Biophys Acta Mol Basis Dis) Vol. 1868 Issue 3 Pg. 166317 (03 01 2022) ISSN: 1879-260X [Electronic] Netherlands
PMID34883248 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2021 Elsevier B.V. All rights reserved.
Chemical References
  • Enzyme Inhibitors
  • hexahydrocurcumin
  • Nitric Oxide
  • Curcumin
  • NG-Nitroarginine Methyl Ester
Topics
  • Animals
  • Blood Pressure
  • Curcumin (analogs & derivatives, pharmacology)
  • Enzyme Inhibitors (toxicity)
  • Hypertension (chemically induced, drug therapy, metabolism, pathology)
  • Male
  • NG-Nitroarginine Methyl Ester (toxicity)
  • Nitric Oxide (metabolism)
  • Oxidative Stress (drug effects)
  • Rats
  • Rats, Wistar
  • Vascular Remodeling (drug effects)

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