Red clover extract ameliorates dyslipidemia in streptozotocin-induced diabetic C57BL/6 mice by activating hepatic PPARα

Phytother Res. 2012 Jun;26(6):860-4. doi: 10.1002/ptr.3641. Epub 2011 Nov 14.

Abstract

The effects of red clover extract and its bioactive components, biochanin A and formononetin, on the blood glucose and lipid levels of streptozotocin (STZ) induced-diabetic mice were investigated. Male diabetic C57BL/6 mice were induced by multiple low-dose STZ administration and then treated with red clover extract or isoflavones for a period of 3 weeks. Red clover extract had no significant effect on lowering the blood glucose levels of STZ-diabetic mice. Similarly, biochanin A and formononetin exerted no hypoglycemic effect. However, the serum triglycerides, total cholesterols and low-density lipoprotein-cholesterol levels for STZ-diabetic mice receiving red clover extract were significantly lower than that of untreated STZ-diabetic mice. In addition, treatment with biochanin A or formononetin significantly ameliorated these lipid profiles in diabetic mice. The mRNA expression of two target genes transcriptionally regulated by peroxisome proliferator-activated receptor (PPAR) α were determined by semi-quantitative RT-PCR and biochanin A or formononetin were found to significantly down-regulate hepatic APOC3 expression, whereas they had no significant effect on hepatic APOA5 expression. Thus we conclude that red clover extract and biochanin A or formononetin significantly ameliorate the lipid profiles of STZ-diabetic mice and these effects are achieved at least in part by activating hepatic PPARα.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoprotein A-V
  • Apolipoprotein C-III / genetics
  • Apolipoprotein C-III / metabolism
  • Apolipoproteins / genetics
  • Apolipoproteins / metabolism
  • Blood Glucose / drug effects
  • Cholesterol, LDL / blood
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / genetics
  • Dyslipidemias / drug therapy*
  • Dyslipidemias / genetics
  • Gene Expression Regulation
  • Genistein / chemistry
  • Genistein / therapeutic use
  • Hypoglycemic Agents / therapeutic use
  • Isoflavones / chemistry
  • Isoflavones / pharmacology
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • PPAR alpha / genetics
  • PPAR alpha / metabolism*
  • Phytotherapy*
  • Plant Extracts / chemistry
  • Plant Extracts / therapeutic use*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Streptozocin / administration & dosage
  • Streptozocin / adverse effects
  • Trifolium / chemistry*
  • Triglycerides / blood

Substances

  • Apoa5 protein, mouse
  • Apolipoprotein A-V
  • Apolipoprotein C-III
  • Apolipoproteins
  • Blood Glucose
  • Cholesterol, LDL
  • Hypoglycemic Agents
  • Isoflavones
  • PPAR alpha
  • Plant Extracts
  • RNA, Messenger
  • Triglycerides
  • formononetin
  • Streptozocin
  • Genistein
  • biochanin A