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A Novel HMG-CoA Reductase Inhibitor from Methanolic Extract of Holoptelea integrifolia (Roxb.) Planch

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Prospects in Bioscience: Addressing the Issues

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Abstract

Holoptelea integrifolia is a large deciduous tree included in lekhaneyagana, a pharmacological classification remarked in Charaka Samhita, which means “reduce excess fat”. The present study was to check the effect of methanolic fraction of H. integrifolia on serum lipids, faecal lipids and HMG-CoA reductase (HMGR), an enzyme which catalyses the committed step in cholesterol biosynthesis. H. integrifolia extracts were administered orally at doses (200 and 400 mg/kg body weight) to diet-induced obese Sprague Dawley (SD) strain rats. Mevinolin was used as positive control. After 4 weeks of administration, the concentrations of total cholesterol (T-c), triglycerides (TG) and low-density lipoprotein (LDL-c) in serum were significantly lower in H. integrifolia-treated groups compared to high-fat group. Both groups showed higher ratio of high-density lipoprotein cholesterol (HDL-c)/(T-c) compared to high-fat diet group. In this study, HMGR activity was enormously reduced, and detailed faecal analysis showed a remarkable increase in faecal T-c and TG compared to high-fat control. It is presumed that a higher hypolipidemic effect of H. integrifolia might be accounted by the combined effect by HMGR inhibition which results in suppression of endogenous cholesterol biosynthesis and blocking the intestinal fat absorption.

The methanolic fraction of H. integrifolia on LCMS and tandem mass spectrometry analysis showed the presence of a compound, 2-[(3,4-dimethyl-2-oxo-2H-chromen-7-yl)oxy] propanoate (C1). The compound C1 was subjected to molecular docking studies with human HMGR (1HW8). The results indicate that the compound C1 can bind strongly to free HMGR in its active site and support the in vivo results. Based on this observation, we propose that the compound C1 is a potent inhibitor of HMGR and hence potential anticholesterol agent.

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Abbreviations

HDL-c:

High-density lipoprotein cholesterol

HMGR:

HMG-CoA reductase

LCMS:

Liquid chromatography mass spectro­metry

LDL-c:

Low-density lipoprotein cholesterol

MSMS:

Tandem mass spectrometry

RT:

Retention time

T-c:

Total cholesterol

TG:

Triglycerides

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Acknowledgements

DBT-BIF, Govt. of India, is gratefully acknowledged for the support in the form of Bioinformatics Infrastructure Facility (BIF) at the Department of Biotechnology and Microbiology, Kannur University, for computational and other allied facilities. Arun KS is thankful to UGC-BSR, New Delhi, for providing the fellowship to carry out the research work.

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Authors and Affiliations

  1. Department of Biotechnology and Microbiology, Kannur University, Thalassery Campus, Kannur, 670661, India

    K. S. Arun & Anu Augustine

  2. Inter University Centre for Bioscience, Kannur University, Kannur, 670661, India

    K. S. Arun & Anu Augustine

Authors
  1. K. S. Arun
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  2. Anu Augustine
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Correspondence to Anu Augustine .

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Editors and Affiliations

  1. , Dept of Biotechnology & Microbiology, Kannur University, Palayad P.O,Thalassery Campus, Kannur, 670661, Kerala, India

    Abdulhameed Sabu

  2. , Dept. of Biotechnology and Microbiology, Kannur University, Palayad P.O, Thalassery Campus, Kannur, 670661, Kerala, India

    Anu Augustine

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Arun, K.S., Augustine, A. (2012). A Novel HMG-CoA Reductase Inhibitor from Methanolic Extract of Holoptelea integrifolia (Roxb.) Planch. In: Sabu, A., Augustine, A. (eds) Prospects in Bioscience: Addressing the Issues. Springer, India. https://doi.org/10.1007/978-81-322-0810-5_7

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