Asiatic Acid Alleviates Hemodynamic and Metabolic Alterations via Restoring eNOS/iNOS Expression, Oxidative Stress, and Inflammation in Diet-Induced Metabolic Syndrome Rats

Poungrat Pakdeechote,Parichat Prachaney,Wilaiwan Khrisanapant,Sarawoot Bunbupha,Upa Kukongviriyapan,Veerapol Kukongviriyapan

doi:10.3390/nu6010355

Abstract

Asiatic acid is a triterpenoid isolated from Centella asiatica. The present study aimed to investigate whether asiatic acid could lessen the metabolic, cardiovascular complications in rats with metabolic syndrome (MS) induced by a high-carbohydrate, high-fat (HCHF) diet. Male Sprague-Dawley rats were fed with HCHF diet with 15% fructose in drinking water for 12 weeks to induce MS. MS rats were treated with asiatic acid (10 or 20 mg/kg/day) or vehicle for a further three weeks. MS rats had an impairment of oral glucose tolerance, increases in fasting blood glucose, serum insulin, total cholesterol, triglycerides, mean arterial blood pressure, heart rate, and hindlimb vascular resistance; these were related to the augmentation of vascular superoxide anion production, plasma malondialdehyde and tumor necrosis factor-alpha (TNF-α) levels (p < 0.05). Plasma nitrate and nitrite (NOx) were markedly high with upregulation of inducible nitric oxide synthase (iNOS) expression, but dowregulation of endothelial nitric oxide synthase (eNOS) expression (p < 0.05). Asiatic acid significantly improved insulin sensitivity, lipid profiles, hemodynamic parameters, oxidative stress markers, plasma TNF-α, NOx, and recovered abnormality of eNOS/iNOS expressions in MS rats (p < 0.05). In conclusion, asiatic acid improved metabolic, hemodynamic abnormalities in MS rats that could be associated with its antioxidant, anti-inflammatory effects and recovering regulation of eNOS/iNOS expression.

Highlights

High-carbohydrate, high-fat (HCHF) diet-induced metabolic and cardiovascular abnormalities in rats that closely mimic characteristics of metabolic syndrome in human have been used in several studies [1,2,3]
A decrease of insulin resistance was more pronounced in 20 mg/kg of asiatic acid treatment in metabolic syndrome (MS) rats
The AUC of glucose concentration during Oral Glucose Tolerance Test (OGTT) was higher in MS rats than in rats fed with a normal diet, indicating glucose intolerance in this group (p < 0.05)

Summary

Introduction

High-carbohydrate, high-fat (HCHF) diet-induced metabolic and cardiovascular abnormalities in rats that closely mimic characteristics of metabolic syndrome in human have been used in several studies [1,2,3]. Metabolic syndrome is an early state of cardiovascular disease and diabetes mellitus which are major causes of serious health problems and increased mortality throughout the world [5,6]. There is evidence to show that an animal model of diet induced-metabolic syndrome is closely linked with oxidative stress [7]. Rats fed with a high-fat diet exhibited metabolic syndrome with an increase in superoxide (O2−) production and subsequent formation of peroxynitrite (ONOO−) that cause inactivation of nitric oxide (NO) [8]. Serum malondialdehyde (MDA), protein carbonyl, C-reactive protein, and xanthine oxidase were increased while superoxide dismutase (SOD)

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