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

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Abstract

Adverse side effects reported for the use of statin drugs provided insights to develop potential anti-dyslipidemic derivatives from natural origin. 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 macroalga Sargassum wightii and β-(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.

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Acknowledgements

The work was assisted by the funding under the Science and Engineering Research Board Scheme (SR/S1/OC-96A/2012) from the Department of Science and Technology, New Delhi, India. The authors thank the Director, Indian Council of Agricultural Research-Central Marine Fisheries Research Institute (ICAR-CMFRI), and Head, Marine Biotechnology Division, ICAR-CMFRI for guidance and support. The authors thank Dr Ramadasan Kuttan, Research Director of Amala Cancer Research Centre, Kerala, for help.

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  1. Marine Bioprospecting Section of Marine Biotechnology Division, Central Marine Fisheries Research Institute, Ernakulam North, P.B. No. 1603, Cochin, India

    Kajal Chakraborty & Anusree Maneesh

  2. Department of Chemistry, Mangalore University, Mangalagangothri, Karnataka, 574199, India

    Anusree Maneesh

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  1. Kajal Chakraborty
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Correspondence to Kajal Chakraborty.

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The animal model experiments were performed after obtaining preliminary acquiescence from the IAEC of Amala Cancer Research Centre, Kerala (permission number ACRC/IAEC/16-06-12), and in accordance with the directive stipulated by CPCSEA, Ministry of Environment and Forest, Government of India, as well as National Institutes of Health guide for the care and use of laboratory animals.

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Chakraborty, K., Maneesh, A. Marine-derived polygalactofucan and its β-2-deoxy-amino-substituted glucopyranan composite attenuate 3-hydroxy-3-methylglutaryl-CoA reductase: prospective natural anti-dyslipidemic leads. Med Chem Res 29, 281–300 (2020). https://doi.org/10.1007/s00044-019-02482-7

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