Marine-derived polygalactofucan and its β -2-deoxy-amino-substituted glucopyranan composite attenuate 3-hydroxy-3-methylglutaryl-CoA reductase: prospective natural anti-dyslipidemic leads

The objective of the work was to develop the marine-derived polysaccharides attenuating 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), and as prospective natural anti-dyslipidemic leads. Physical and chromatographic purification methods were used to isolate the polygalactofucan from the marine macroalgaSargassum wightii andβ-(2-deoxy)-amino-substituted glucopyrananan from a marine crustacean. Glycosidic linkage analysis by the process of methylation was used for structural elucidation of the polygalactofucan, and the methylated and partially methylated alditol acetates were characterized using extensive spectroscopic experiments. The polysaccharide composite constituting the titled polysaccharide motifs showed significant HMGCR inhibitory potential (IC90 0.12  mg mL−1) and an increase in HMG-CoA/mevalonate ratio (1.68  mg dL−1) compared with the high-fat diet (HFD)-treated animals (1.04  mg dL−1), which recognized its hypo-lipidemic efficacy. In vivo results demonstrated about 70% reduction in the triglyceride levels with the concomitant increase (~39%) of hepatic lipoprotein lipase (LPL) activity in the HFD-fed Wistar rats treated with 500  mg kg−1 body weight. The results illustrated the use of marine-derived polygalactofucan composite as potential anti-dyslipidemic agent.
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research