Lipid-lowering efficacy of hesperetin metabolites in high-cholesterol fed rats

Clin Chim Acta. 2003 Jan;327(1-2):129-37. doi: 10.1016/s0009-8981(02)00344-3.


Background: Hesperetin is a naturally occurring flavonoid that has hypolipidemic properties.

Methods: Male rats were fed a 1 g/100 g high-cholesterol diet for 5 weeks along with hesperetin (0.02%, 0.066 mmol/100 g diet) and hesperetin metabolites. The hesperetin metabolites, m-hydroxycinnamic acid (m-HC), 3,4-dihydroxyphenylpropionic acid (3,4-DHPP), and 3-methoxy-4-hydroxycinnamic acid (ferulic acid), were supplemented based on an equivalent amount of hesperetin.

Results: The supplementation of hesperetin and its metabolites significantly lowered the plasma total cholesterol and triglyceride concentrations compared to the control group. The hepatic HMG-CoA reductase and acyl-CoA:cholesterol acyltransferase (ACAT) activities were significantly lower in the hesperetin and its metabolite supplemented groups than in the control group. The excretion of acidic sterol was significantly higher in the hesperetin, m-HC, 3,4-DHPP, and ferulic acid supplemented groups than in the control group.

Conclusions: These results demonstrated that the hesperetin metabolites played as potent a role as hesperetin in plasma lipid-lowering activities in vivo, and further suggest that cholesterol biosynthesis and esterification were concomitantly reduced by hesperetin and its metabolites, as indicated by the decreased HMG-CoA reductase and ACAT activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caffeic Acids / administration & dosage
  • Caffeic Acids / pharmacology
  • Cholesterol / blood
  • Cholesterol, Dietary / administration & dosage*
  • Coumaric Acids / administration & dosage
  • Coumaric Acids / pharmacology
  • Hesperidin / administration & dosage
  • Hesperidin / metabolism
  • Hesperidin / pharmacology*
  • Hydroxymethylglutaryl CoA Reductases / blood
  • Hydroxymethylglutaryl CoA Reductases / drug effects
  • Lipids / blood*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Sterol O-Acyltransferase / blood
  • Sterol O-Acyltransferase / drug effects
  • Triglycerides / blood


  • Caffeic Acids
  • Cholesterol, Dietary
  • Coumaric Acids
  • Lipids
  • Triglycerides
  • 3,4-dihydroxyphenylpropionic acid
  • Cholesterol
  • ferulic acid
  • Hesperidin
  • Hydroxymethylglutaryl CoA Reductases
  • Sterol O-Acyltransferase
  • hesperetin