Evaluation of the combination of Kemuning Leaves Extracts and Simvastatin on Blood fatty acids and amino acids of Hyperlipidemic Model Rats

Abstract

Introduction: Hypercholesterolemia is an increase in cholesterol levels and a high risk of cardiovascular disease. Simvastatin, a cholesterol-lowering agent, is commonly applied in hypercholesterolemic patients. Simvastatin is metabolized by CYP3A4 so that any drugs that block CYP3A4 will elevate the statin level in the blood. Kemuning leaves (Murraya paniculata L.) contain Mahanimbine, has been known to have an antihyperlipidemic effect. Some people used Kemuning leaves besides to simvastatin treatment so that the interaction between the two substances can occur. The aims of this study to determine the effects of the combination of Kemuning leaves extracts with simvastatin. Method: Six-weeks-old male Wistar rats were randomly divided into nine experimental groups (n = 5 per group). The rat of two groups was fed with a regular diet or with a high-fat diet (HFD) for five weeks. The daily food and HFD groups were administered with 0.5% Carboxymethylcellulose (CMC) as a vehicle or suspension of Simvastatin 2.04 mg/kg of body weight or Kemuning leaves extracts 100, 200, and 400 mg/kg body weight. During the whole treatment, body weight and food intake were recorded every week. Lipid profile was evaluated by spectrophotometric method; amino acid concentration and fatty acid concentration were determined using LCMS-MS. Results: In vivo experiment showed that a single administration of simvastatin and three different doses of Kemuning extracts could reduce the high level of total cholesterol, LDL-cholesterol, and Triglyceride in the hyperlipidemic model rat. But when simvastatin was combined with three kinds of doses of Kemuning extracts, the value had the tendency to show lower than a single administration of simvastatin either Kemuning extracts. We confirmed the lipid and amino acid profiles in plasma and found that similar results. Conclusion: This study indicated that the single administration of simvastatin or Kemuning extract was better than combining them because the combination was causing interaction of each of them by influence fatty acid and amino acids metabolism.