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.