4.7 Article

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

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ELSEVIER
DOI: 10.1016/j.bbadis.2021.166317

Keywords

Hexahydrocurcumin; Hypertension; Vascular dysfunction; Vascular remodeling

Funding

  1. Functional Food Research Center for Well-Being, Chiang Mai University
  2. Thailand Research Fund [DBG6180030]
  3. Center of Excellence for Innovation in Chemistry, Ministry of Higher Education
  4. Royal Golden Jubilee (RGJ) PhD program by National Research Council of Thailand (NRCT) [PHD/0107/2561]

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The study found that HHC can improve vascular function and attenuate vascular remodeling in hypertensive rats. Its potential mechanisms of action may involve antioxidant and anti-inflammatory effects.
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 hyper -tension, 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-kB), vascular cell adhesion molecule 1 (VCAM1), intercellular adhesion molecule 1 (ICAM1), tumor necrosis factor-alpha (TNF-alpha), 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-beta 1), 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 alter-ations 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.

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