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

Luckika Panthiya; Jiraporn Tocharus; Amnart Onsa-Ard; Waraluck Chaichompoo; Apichart Suksamrarn; Chainarong Tocharus

doi:10.1016/j.bbadis.2021.166317

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

Biochim Biophys Acta Mol Basis Dis. 2022 Mar 1;1868(3):166317. doi: 10.1016/j.bbadis.2021.166317. Epub 2021 Dec 7.

Authors

Luckika Panthiya¹, Jiraporn Tocharus², Amnart Onsa-Ard³, Waraluck Chaichompoo⁴, Apichart Suksamrarn⁴, Chainarong Tocharus⁵

Affiliations

¹ Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; Graduate School, Chiang Mai University, Chiang Mai 50200, Thailand.
² Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
³ Division of Biochemistry, School of Medical Sciences, University of Phayao, Phayao 56000, Thailand.
⁴ Department of Chemistry and Center of Excellence of Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok 10240, Thailand.
⁵ Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; Functional Food Research Center for Well-Being, Chiang Mai University, Chiang Mai 50200, Thailand. Electronic address: chainarong.t@cmu.ac.th.

PMID: 34883248
DOI: 10.1016/j.bbadis.2021.166317

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.

Keywords: Hexahydrocurcumin; Hypertension; Vascular dysfunction; Vascular remodeling.

Publication types

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

MeSH terms

Animals
Blood Pressure
Curcumin / analogs & derivatives*
Curcumin / pharmacology
Enzyme Inhibitors / toxicity
Hypertension / chemically induced
Hypertension / drug therapy*
Hypertension / metabolism
Hypertension / pathology
Male
NG-Nitroarginine Methyl Ester / toxicity*
Nitric Oxide / metabolism*
Oxidative Stress / drug effects*
Rats
Rats, Wistar
Vascular Remodeling / drug effects*

Substances

Enzyme Inhibitors
hexahydrocurcumin
Nitric Oxide
Curcumin
NG-Nitroarginine Methyl Ester