ABSTRACT
Nonalcoholic fatty liver disease (NAFLD) is a chronic disease that causes morbidity associated with metabolic syndrome. NAFLD is a worldwide problem and represents a major cause of liver injury, which can lead to liver cell death. We investigated the effects of nonivamide (pelargonic acid vanillylamide, PAVA; 1 mg/kg) and rosuvastatin (RSV; 10 mg/kg) on hepatic steatosis induced by a high-fat diet (HFD). Male Sprague-Dawley rats were fed a HFD for 16 weeks then received PAVA or RSV for 4 additional weeks. We examined the metabolic parameters, function, fat content, histological alterations, reactive oxygen species production, and apoptotic cell death of the liver, in addition to the expression of the following important molecules: transient receptor potential cation channel subfamily V member 1 (TRPV1) phosphorylation of sterol regulatory element binding protein (pSREBP-1c/SREBP-1c), total and membrane glucose transporter 2 (GLUT2), 4-hydroxynonenal (4-HNE), and cleaved caspase-3. HFD-induced hepatic steatosis was associated with significantly increased morphological disorganization, injury markers, oxidative stress, lipid peroxidation, and apoptosis. However, metabolic dysfunction and hepatic injury were reduced by RSV and PAVA treatment. PAVA regulated lipid deposition, improved insulin resistance, and decreased oxidative stress and apoptotic cell death. Therefore, PAVA represents a promising therapeutic approach for treating metabolic disorders in patients with NAFLD.
Subject(s)
Capsaicin/analogs & derivatives , Capsicum/chemistry , Diet, High-Fat/adverse effects , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/etiology , Phytotherapy , Aldehydes/metabolism , Animals , Apoptosis/drug effects , Capsaicin/administration & dosage , Capsaicin/isolation & purification , Capsaicin/pharmacology , Caspase 3/metabolism , Glucose Transporter Type 2/metabolism , Lipid Peroxidation/drug effects , Liver/metabolism , Liver/pathology , Male , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/pathology , Oxidative Stress/drug effects , Rats, Sprague-Dawley , Rosuvastatin Calcium/administration & dosage , Rosuvastatin Calcium/pharmacology , Sterol Regulatory Element Binding Protein 1/metabolism , TRPV Cation Channels/metabolismABSTRACT
Capsaicinoid nonivamide (PAVA) and rosuvastatin (RSV) have been shown to exert antioxidant and anti-obesity effects in various animal models, but it is unknown whether their combination would be an effective treatment for obesity-related endothelial dysfunction. This study aimed to investigate the mechanism of PAVA in synergy with RSV. Male Sprague-Dawley rats were given a high-fat diet (HFD) or normal diet during a 20-week period. At 16 weeks, rats in each diet group were divided into subgroups. Normal diet rats were divided into Normal diet control, Normal diet with PAVA, and Normal diet with RSV groups. HFD rats were subdivided into HFD control, HFD with PAVA, HFD with RSV, and HFD with PAVA + RSV groups and evaluated for metabolic parameters, blood pressure, aortic function, and histological change of the aorta in rats. Our results showed the combined therapy had a significantly greater effect than the monotherapy in all measured parameters; this was indicated by improvement in insulin sensitivity and aortic function, decreased blood pressure, lower oxidative stress, and prevention of vascular damage. The synergistic effect of the PAVA and RSV can protect HFD-induced obesity-related endothelial dysfunction, suggesting that the combination of PAVA and RSV could be an effective alternative treatment for obesity-related complications in patients with cardiovascular disease.