Carthamus Tinctorius L. extract attenuates cardiac remodeling in L-NAME-induced hypertensive rats by inhibiting the NADPH oxidase-mediated TGF-β1 and MMP-9 pathway

Ann Anat. 2019 Mar:222:120-128. doi: 10.1016/j.aanat.2018.12.006. Epub 2018 Dec 24.

Abstract

Carthamus tinctorius L. (CT) has been widely used in Asian countries as a beverage and a folk medicine. The current study investigates the effect of CT extract on cardiac remodeling and possible mechanisms involved in Nw-nitro-l-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. Male Sprague-Dawley rats were administrated with L-NAME (40mg/kg/day) for five weeks to induce hypertension. Hypertensive rats were treated with CT extract (300mg/kg/day) or captopril (5mg/kg/day) or vehicle for a further two weeks. Treatment of hypertensive rats with CT extract or captopril significantly decreased systolic blood pressure, left ventricular (LV) hypertrophy and fibrosis, small intramyocardial coronary artery remodeling, and cardiac weight index. CT extract or captopril increased plasma nitric oxide metabolite (NOx) levels and reduced plasma transforming growth factor β1 (TGF-β1) level, together with downregulation of cardiac TGF-β1 and matrix metalloproteinases-9 (MMP-9) expression. In addition, decreased plasma malondialdehyde (MDA) levels, consistent with downregulation of NADPH oxidase subunit gp91phox expression in heart tissue, was also observed after CT extract or captopril treatment. These findings suggest that CT extract alleviates cardiac remodeling in L-NAME-induced hypertensive rats, which is possibly related to inhibition of the NADPH oxidase-mediated TGF-β1-MMP-9 pathway.

Keywords: Cardiac remodeling; Carthamus tinctorius L.; Hypertension; L-NAME.

MeSH terms

  • Animals
  • Antihypertensive Agents / therapeutic use*
  • Blood Pressure
  • Captopril / therapeutic use
  • Carthamus tinctorius / chemistry*
  • Enzyme Inhibitors*
  • Hypertension / chemically induced*
  • Hypertension / drug therapy*
  • Hypertrophy, Left Ventricular / drug therapy
  • Male
  • Matrix Metalloproteinase 9 / drug effects*
  • Matrix Metalloproteinase Inhibitors / pharmacology*
  • NADPH Oxidases / antagonists & inhibitors*
  • NG-Nitroarginine Methyl Ester*
  • Plant Extracts / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects*
  • Transforming Growth Factor beta1 / antagonists & inhibitors*
  • Ventricular Remodeling / drug effects*

Substances

  • Antihypertensive Agents
  • Enzyme Inhibitors
  • Matrix Metalloproteinase Inhibitors
  • Plant Extracts
  • Tgfb1 protein, rat
  • Transforming Growth Factor beta1
  • Captopril
  • NADPH Oxidases
  • Matrix Metalloproteinase 9
  • NG-Nitroarginine Methyl Ester