Citrus reticulata peel oil as an antiatherogenic agent: Hypolipogenic effect in hepatic cells, lipid storage decrease in foam cells, and prevention of LDL oxidation

Nutr Metab Cardiovasc Dis. 2020 Aug 28;30(9):1590-1599. doi: 10.1016/j.numecd.2020.04.033. Epub 2020 May 12.

Abstract

Background and aims: Hypercholesterolemia and oxidative stress are two of the most important risk factors for atherosclerosis. The aim of the present work was to evaluate mandarin (Citrus reticulata) peel oil (MPO) in cholesterol metabolism and lipid synthesis, and its antioxidant capacity.

Methods and results: Incubation of hepatic HepG2 cells with MPO (15-60 μL/L) reduced cholesterogenesis and saponifiable lipid synthesis, demonstrated by [14C]acetate radioactivity assays. These effects were associated with a decrease in a post-squalene reaction of the mevalonate pathway. Molecular docking analyses were carried out using three different scoring functions to examine the cholesterol-lowering property of all the components of MPO against lanosterol synthase. Docking simulations proposed that minor components of MPO monoterpenes, like alpha-farnesene and neryl acetate, as well the major component, limonene and its metabolites, could be partly responsible for the inhibitory effects observed in culture assays. MPO also decreased RAW 264.7 foam cell lipid storage and its CD36 expression, and prevented low-density lipoprotein (LDL) lipid peroxidation.

Conclusion: These results may imply a potential role of MPO in preventing atherosclerosis by a mechanism involving inhibition of lipid synthesis and storage and the decrease of LDL lipid peroxidation.

Keywords: Citrus reticulata peel oil; Docking; Foam cells; Hepatic cells; Lanosterol synthase; Lipid metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology*
  • Atherosclerosis / etiology
  • Atherosclerosis / metabolism
  • Atherosclerosis / prevention & control*
  • CD36 Antigens / metabolism
  • Cholesterol / metabolism*
  • Citrus* / chemistry
  • Dyslipidemias / complications
  • Dyslipidemias / drug therapy*
  • Dyslipidemias / metabolism
  • Foam Cells / drug effects*
  • Foam Cells / metabolism
  • Fruit* / chemistry
  • Hep G2 Cells
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Humans
  • Hypolipidemic Agents / isolation & purification
  • Hypolipidemic Agents / pharmacology*
  • Intramolecular Transferases / antagonists & inhibitors
  • Intramolecular Transferases / metabolism
  • Lipid Peroxidation / drug effects
  • Lipoproteins, LDL / metabolism*
  • Mice
  • Molecular Docking Simulation
  • Plant Oils / isolation & purification
  • Plant Oils / pharmacology*
  • RAW 264.7 Cells

Substances

  • Antioxidants
  • CD36 Antigens
  • Cd36 protein, mouse
  • Hypolipidemic Agents
  • Lipoproteins, LDL
  • Plant Oils
  • oxidized low density lipoprotein
  • Cholesterol
  • Intramolecular Transferases
  • lanosterol synthase