The extract of Ilex kudingcha inhibits atherosclerosis in apoE-deficient mice by suppressing cholesterol accumulation in macrophages

Biosci Biotechnol Biochem. 2021 Sep 22;85(10):2177-2184. doi: 10.1093/bbb/zbab140.

Abstract

It was previously reported that oleanolic acid and ursolic acid, triterpenoid compounds occurring in Ilex kudingcha, ameliorate hyperlipidemia and atherosclerosis in apoE-deficient mice. In the present study, we investigated whether I. kudingcha extract exerts similar inhibitory effects on cholesterol accumulation in human monocyte-derived macrophages (HMDMs) and atherogenesis in apoE-deficient mice. I. kudingcha extract significantly inhibited cholesterol ester (CE) accumulation induced by acetylated LDL (acetyl-LDL) in HMDMs; however, it generated no effect on cell viability in HMDMs. I. kudingcha extract also suppressed CE accumulation in acyl-CoA:cholesterol acyl-transferase (ACAT)-overexpressing Chinese hamster ovary (CHO) cells, thereby indicating that it inhibits ACAT activity. Furthermore, the oral administration of I. kudingcha extract to apoE-deficient mice significantly decreased the levels of serum cholesterol, triglyceride, sLOX-1, as well as the regions of atherosclerotic lesions in the mice. Our study reveals crucial new-found evidence that I. kudingcha extract significantly inhibits ACAT activity and suppresses atherogenesis.

Keywords: Ilex kudingcha; acyl-CoA:cholesterol acyl-transferase; atherosclerosis; macrophage.

MeSH terms

  • Animals
  • Apolipoproteins E* / deficiency
  • Apolipoproteins E* / genetics
  • Atherosclerosis* / drug therapy
  • Atherosclerosis* / metabolism
  • Atherosclerosis* / pathology
  • Atherosclerosis* / prevention & control
  • CHO Cells
  • Cell Survival / drug effects
  • Cholesterol Esters / metabolism
  • Cholesterol* / blood
  • Cholesterol* / metabolism
  • Cricetulus*
  • Humans
  • Ilex* / chemistry
  • Lipoproteins, LDL / metabolism
  • Macrophages* / drug effects
  • Macrophages* / metabolism
  • Male
  • Mice
  • Mice, Knockout, ApoE
  • Plant Extracts* / pharmacology
  • Sterol O-Acyltransferase / genetics
  • Sterol O-Acyltransferase / metabolism
  • Triglycerides / blood
  • Triglycerides / metabolism

Substances

  • Plant Extracts
  • Cholesterol
  • Apolipoproteins E
  • Triglycerides
  • Sterol O-Acyltransferase
  • acetyl-LDL
  • Cholesterol Esters
  • Lipoproteins, LDL