RESUMEN
OBJECTIVE: High-density lipoprotein (HDL) cholesterol-mediated atherosclerotic plaque regression has gained wide therapeutic attention. The whole plant methanolic extract of the medicinal plant Desmodium gyrans Methanolic Extract (DGM) has shown to mitigate hyperlipidemia in high fat- and-cholesterol fed rats and rabbits with significant HDL enhancing property. The study aimed to assess the functionality and mechanistic basis of HDL promoting effect of DGM. MATERIALS AND METHODS: Macrophage cholesterol efflux and foam cell formation assays were performed in THP-1 macrophages. Male Wistar rats were given DGM extract over 1 month and assessed the serum HDL, Apolipoprotein A1 (Apo-A1), and paraoxonase activity. Quantitative Polymerase chain reaction was carried out to assess the expression level of Apo-A1, SR-B1 (Scavenger receptor B1), and Cholesteryl ester transfer protein (CETP) on cDNA of HepG2 cells exposed to DGM. RESULTS: Pretreatment of DGM inhibited uptake of oxidized lipids and enhanced the lipid efflux by THP-1-derived macrophages. Oral administration of DGM (100 and 250 mg/kg) progressively enhanced the serum HDL, Apo-A1 level, and associated paraoxonase activity in normal male Wistar rats. In support to this, DGM exposed HepG2 cells documented dose-dependent increase in the expression of SR-B1 and Apo-A1 mRNA, while reduced the CETP expression. CONCLUSION: Overall the results indicated that DGM modulates lipid trafficking and possesses functional HDL enhancing potential through increased Apo-A1 levels and paraoxonase activity. Further, reduced CETP expression and increased expression of SR-B1 suggest the reverse cholesterol transport promoting role of DGM.
Asunto(s)
Fabaceae , Metabolismo de los Lípidos/efectos de los fármacos , Lipoproteínas HDL/fisiología , Macrófagos/metabolismo , Extractos Vegetales/farmacología , Animales , Apolipoproteína A-I/genética , Antígenos CD36/genética , Proteínas de Transferencia de Ésteres de Colesterol/genética , Células Espumosas/fisiología , Células Hep G2 , Humanos , Masculino , Ratas , Ratas Wistar , Células THP-1RESUMEN
A polyherbal formulation consisting of different proportions of Commiphora mukul (Hook ex Stocks) Eng., Salacia reticulata Wight, Terminalia arjuna (Roxb.) Wight & Arn, and Curcuma longa Linn extracts was tested for free-radical scavenging and anti-lipid peroxidative effects on serum and platelets in vitro. The most active formulation (GSTC3) was evaluated for its hypolipidemic potential on a high-fat, high-cholesterol diet (HFD) fed to male Wistar rats for a period of 45 days. At a dose of 100 mg/kg body weight, GSTC3 decreased serum total cholesterol, low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), triglycerides, and phospholipids similar to standard atorvastatin while maintaining high-density lipoprotein (HDL) at normal levels. Significantly lower levels of thiobarbituric acid-reactive substances (TBARS) were observed in both the liver and sera of rats treated with GSTC3. Although the phospholipid levels in liver remained unchanged, lower values of LDL, VLDL, and atherogenic index of plasma as well as higher HMG-CoA/ mevalonate ratios suggested a significant hypolipidemic effect for GSTC3, possibly by partial inhibition of HMG-CoA reductase activity. The histopathological analysis of liver tissue did not reveal lipid accumulation or indicate tissue damage. Overall, the results of this study suggest the hypolipidemic and anti-atherogenic efficacy of a nontoxic herbal formulation.