Asiatic acid alleviates metabolic and hemodynamic alterations in high-fat, high-carbohydrate diet-induced metabolic syndrome rats.

Consumption of high-fat, high-carbohydrate diet mainly contributed in the development of metabolic syndrome, which is associated with obesity, insulin resistance, dyslipidemia, and high blood pressure. It is well established that asiatic acid, a natural triterpenoid compound derived from Centella asiatica, exhibited biological effects including, antiinflammation, antioxidant and antihyperglycemia. In the present study, we examined the metabolic, cardiovascular responses as well as antioxidant properties of asiatic acid in rats with metabolic syndrome (MS) induced by high-fat, high-carbohydrate (HFHC) diet. Male Sprague-Dawley rats (160-180 g) were fed with HFHC diet with 15% fructose in drinking water for 12 weeks to induce MS. Then, MS rats and normal rats received asiatic acid (10 mg/kg) or vehicle for further 3 weeks. Fasting serum insulin, fasting blood glucose (FBG), oral glucose tolerance test (OGTT) and systolic blood pressure (SBP) were measured once a month. At the end of treatment, rats were anaesthetized with peritoneal injection of pentobarbital-sodium (60 mg/kg) and hemodynamic status, lipid profiles and oxidative stress markers were evaluated. All procedures are complied with the standards for the care and use of experimental animals and approved by Animal Ethics Committee of Khon Kaen University, Khon Kaen, Thailand (AEKKU 36/2555). Data are expressed as the mean ± S.E.M., compared by ANOVA. Results showed that rats fed with HFHC diet had an impairment of OGTT, high homeostasis model assessment of insulin (HOMA-IR), high cholesterol, and high SBP, indicating metabolic syndrome (MS) in these rats (p<0.05). Moreover, mean arterial blood pressure (MAP) (MS: 114.61 ± 3.7 vs. 90.58 ± 1.7 mmHg control, p<0.05), hindlimb vascular resistance (HVR) (MS: 30.64 ± 2.5 vs. 11.46 ± 0.6 mmHg/min/100 g/ml control, p<0.05) were significantly increased, relating to the augmentation of vascular superoxide production (MS: 114.9 ± 15.1 vs. 56.9 ± 4.3 counts/min/mg dry weight control, p<0.05) and plasma MDA levels (MS: 5.8 ± 0.5 vs. 2.9 ± 0.2 µM control, p<0.05) in MS group. Treatment with asiatic acid significantly attenuated dyslipidemia and improved insulin sensitivity as shown by the decreased HOMA-IR (p<0.05). We found reductions in MAP (about 11 .4%) and HVR (about 36%) in MS rats received asiatic acid (p<0.05). Moreover, asiatic acid exhibited antioxidant properties by markedly reducing oxidative stress markers in vascular tissues and plasma in MS rats (p<0.05). In conclusion, asiatic acid improved metabolic and hemodynamic changes as well as oxidative stress in HFHC diet induced MS rats. [ABSTRACT FROM AUTHOR]