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Novel quercetin-3-O-glucoside eicosapentaenoic acid ester ameliorates inflammation and hyperlipidemia

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Abstract

Quercetin, a major flavonol, present abundantly in apples and onions, is widely studied for ameliorating metabolic syndrome abnormalities. However, quercetin is mainly present in plant food in the form of quercetin glycosides and has been reported for poor gastrointestinal absorption. The present study was designed with the purpose of imparting a lipophilic property to quercetin-3-O-glucoside (QG) by its acylation with eicosapentaenoic acid (EPA) and to study the influence of eicosapentaenoic acid ester of quercetin-3-O-glucoside (QE) on hyperlipidemia and inflammation in vivo and in vitro. QE was more effective in reducing the production of tumor necrosis factor-alpha (TNF-α), prostaglandin 2 (PGE2), cyclo-oxygenase (COX)-2 levels and nuclear expression of nuclear factor-kappa B (NF-кB) compared to the parent compounds (QG and EPA) and commercial drugs, after lipopolysaccharides (LPS) induced inflammation in THP-1 derived macrophages. Serum high-density lipoprotein (HDL)-cholesterol was significantly higher and hepatic total cholesterol concentration was lower in the rats fed high-fat diet supplemented with QE, compared to the high-fat diet with inflammation (HFL). The serum concentrations of C-reactive protein (CRP), interleukin (IL)-6, and interferon-gamma (IFN-γ) were significantly lower in QE treatment group than HFL group. EPA conjugated flavonol, QE, had significant anti-inflammatory and hypolipidemic properties and may be effective for the treatment of obesity-related disorders.

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Abbreviations

CRP:

C-reactive protein

HFC:

High fat control

HFL:

High fat with lipopolysaccharide

LPS:

Lipopolysaccharide

QG:

Quercetin-3-O-glucoside

QE:

Eicosapentaenoic acid ester of quercetin-3-O-glucoside

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Acknowledgments

The authors acknowledge the funding provided by the Discovery Grant program of the Natural Sciences and Engineering Research Council (NSERC) of Canada and the Atlantic Innovation Funds Program of the Atlantic Canada Opportunities Agency (ACOA).

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Author notes

  1. Marianna Kulka

    Present address: National Institute for Nanotechnology, National Research Council of Canada, Edmonton, AB, T6G 2M9, Canada

Authors and Affiliations

  1. Department of Environmental Sciences, Faculty of Agriculture, Dalhousie University, P.O. Box 550, Truro, NS, B2N 5E3, Canada

    Satvir Sekhon-Loodu, Ziaullah Ziaullah & H. P. Vasantha Rupasinghe

  2. Departments of Pharmacology and Pathology, Faculty of Medicine, Dalhousie University, Halifax, NS, B3H 4R2, Canada

    H. P. Vasantha Rupasinghe

  3. Aquatic and Crop Resource Development, National Research Council of Canada, Charlottetown, PE, C1A 4P3, Canada

    Yanwen Wang & Marianna Kulka

  4. Department of Biochemistry, Memorial University of Newfoundland, St. John’s, NL, A1B 3X9, Canada

    Fereidoon Shahidi

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  1. Satvir Sekhon-Loodu
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Correspondence to H. P. Vasantha Rupasinghe.

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Sekhon-Loodu, S., Ziaullah, Z., Rupasinghe, H.P.V. et al. Novel quercetin-3-O-glucoside eicosapentaenoic acid ester ameliorates inflammation and hyperlipidemia. Inflammopharmacol 23, 173–185 (2015). https://doi.org/10.1007/s10787-015-0237-0

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