Desmodium gyrans dc modulates lipid trafficking in cultured macrophages and improves functional high-density lipoprotein in male wistar rats.

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.

Non-enzymatic conversion of primary oxidation products of Docosahexaenoic acid into less toxic acid molecules.

Docosahexaenoic acid (DHA) is long chain omega-3 fatty acid with known health benefits and clinical significance. However, 4-hydroxy hexenal (HHE), an enzymatic oxidation product of DHA has recently been reported to have health-damaging effects. This conflict raises major concern on the long-term clinical use of these fatty acids. Even though the enzymatic and non-enzymatic conversion of HHE to nontoxic acid molecules is possible by the aldehyde detoxification systems, it has not yet studied. To address this, primary oxidation products of DHA in lipoxidase system were subjected to non-enzymatic conversion at physiological temperature over a period of 1 week. The reaction was monitored using HPLC, IR spectroscopy and biochemical assays (based on the loss of conjugated dienes, lipid peroxides aldehydes). Short term and long term cytotoxicity of the compounds generated at various time points were analyzed. IR and HPLC spectra revealed that the level of aldehydes in the primary oxidation products reduced over time, generating acids and acid derivatives within a week period. In short term and long term cytotoxicity analysis, initial decomposition products were found more toxic than the 1-week decomposition products. Further, when primary oxidation products were subjected to aldehyde dehydrogenase mediated oxidation, it generated products that are also less toxic. The study suggests the possible non-enzymatic conversion of primary oxidation products of DHA to less cytotoxic acid molecules. Exploration of the physiological roles of these acid molecules may explain the biological potential of omega-3 fatty acids.

Virgin coconut oil maintains redox status and improves glycemic conditions in high fructose fed rats.

Virgin Coconut Oil (VCO), extracted from fresh coconut kernel possess similar fatty acid composition to that of Copra Oil (CO), a product of dried kernel. Although CO forms the predominant dietary constituent in south India, VCO is being promoted for healthy life due to its constituent antioxidant molecules. High fructose containing CO is an established model for insulin resistance and steatohepatitis in rodents. In this study, replacement of CO with VCO in high fructose diet markedly improved the glucose metabolism and dyslipidemia. The animals fed VCO diet had only 17 % increase in blood glucose level compared to CO fed animals (46 %). Increased level of GSH and antioxidant enzyme activities in VCO fed rats indicate improved hepatic redox status. Reduced lipid peroxidation and carbonyl adducts in VCO fed rats well corroborate with the histopathological findings that hepatic damage and steatosis were comparatively reduced than the CO fed animals. These results suggest that VCO could be an efficient nutraceutical in preventing the development of diet induced insulin resistance and associated complications possibly through its antioxidant efficacy.

Development of an Anti-Atherosclerotic Polyherbal Formulation: GSTC3.

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.