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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. Copyright © 2011 John Wiley & Sons, Ltd.