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

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.

Neuroprotective Effect of Asiatic Acid in Rat Model of Focal Embolic Stroke

“…7,8) AA inhibits adipogenic differentiation of bone marrow stromal cells and attenuates ethanol-induced hepatic injury via suppression of oxidative stress and Kupffer cell activation. 9,10) …”

“…6) Also, AA was recently reported to alleviate hemodynamic and metabolic alterations via restoring endothelial nitric oxide synthase (eNOS)/inducible nitric oxide synthase (iNOS) expression, oxidative stress, and inflammation in diet-induced metabolic syndrome rats and to regulates the carbohydrate metabolism by modulating the key regulatory enzymes in diabetic rats. 7,8) AA inhibits adipogenic differentiation of bone marrow stromal cells and attenuates ethanol-induced hepatic injury via suppression of oxidative stress and Kupffer cell activation. 9,10) Previously, we reported that AA is neuroprotective in mouse and rat models of focal ischemia.…”

Aldehyde Dehydrogenase-2 Attenuates Myocardial Remodeling and Contractile Dysfunction Induced by a High-Fat Diet

“…We observed reduced EF and FS, enlarged LVEDD and LVESD, elevated IVSd and LVPWd, and excessive apoptosis, deposition of lipid droplets, and collagen fibers in cardiomyocytes of MS mice. Several mechanisms may be responsible for these MS-related abnormalities, including impaired insulin resistance and increased oxidative stress [23,24]. In this study, impaired insulin resistance may underscore the accelerated apoptosis and myocardial fibrosis in cardiac tissue of MS mice induced by a HF diet.…”

Severe Malarial Anemia (SMA) Pathophysiology and the Use of Phytotherapeutics as Treatment Options

“…The effect of AA in alleviating hemodynamic and metabolic alterations in metabolic syndrome is through restoration of endothelium nitric oxide synthase (eNOS)/iNOS expression [93]. Similar influence of AA in malaria may be anticipated where eNOS/iNOS ratio determines the bioavailability of NO necessary for vascular proliferation and angiogenesis.…”

“…The anti-inflammatory mechanism involved selective cytotoxicity to activated macrophage cell line (L-929). By upregulating the expression of apoptosis-inducing genes caspase-8, c-myc, inducible nitric oxide synthase (iNOS), mdm2, NF-kβα, I-kβα and NF-kβ p105, the phytotherapeutics controlled inflammation [93]. This alludes to AA exerting anti-inflammatory effect by cytochrome c release, caspase 3 activation and poly (ADP-ribose) polymerase cleavage mechanism as did AS2006A [92].…”