👤 Jose Padikkala

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. 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. 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. 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. Show less

Apart from the conventional hypolipidemic therapy, plaque regression through enhanced reverse cholesterol transport (RCT) has emerged as novel approach in atherosclerotic drug development. High-density lipoprotein (HDL) mimetics as well as agents that augment the functional HDL and RCT pathways are under intense exploration. Desmodium gyrans (Fabacea) has been shown to have hypolipidemic efficacy, with an HDL-enhancing property. In this study, a chromatographically purified active fraction of D. gyrans (DGMAF) significantly decreased the serum and lipid profiles as well as lipotoxicity in liver in Wistar rats fed with high-fat diet (HFD). Except for the marginal deposition of liver lipids, all other organs showed no weight gain due to lipid accumulation. A lower level of lipid peroxidation and a reduced atherogenic index suggests the hypolipidemic efficacy of DGMAF, which was comparatively higher than clinically used atorvastatin. Furthermore, the DGMAF-treated animals had enhanced levels of HDL, associated ApoA-1, and paraoxonase activity. The mRNA levels of ApoA-1 and SR-B1 were upregulated, and cholesteryl ester transfer protein (CETP) was downregulated. Overall, the results of this study indicate that D. gyrans augments the RCT pathway and improves the lipid metabolism in rats fed an HFD. Show less