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

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.