Red clover extract exerts antidiabetic and hypolipidemic effects in db/db mice

To investigate the effects of red clover extract on the blood glucose and lipid levels of type 2 diabetic db/db mice, male db/db mice were treated with this extract for a period of 5 weeks. The red clover extract had a significant effect on lowering the blood glucose levels of db/db mice. The serum triglyceride, serum total cholesterol, liver triglyceride and liver cholesterol levels for diabetic mice receiving red clover extract were significantly lower compared to those of the untreated diabetic mice. The mRNA expression of two target genes transcriptionally regulated by peroxisome proliferator-activated receptor (PPAR)γ was determined by quantitative real-time RT-PCR, and red clover extract was observed to significantly upregulate hepatic glucokinase and CD36 expression. Four target genes transcriptionally regulated by PPARα were also assayed, and red clover extract was observed to significantly downregulate hepatic apolipoprotein C3 expression whereas it had no significant effect on apolipoprotein A5, acetyl CoA oxidase and carnitine palmitoyl transferase-1 expression. In addition, hepatic mRNA expression of fatty acid synthase was also observed to be downregulated by red clover extract treatment. Thus, we conclude that red clover extract significantly improves the glucose and lipid homeostasis in db/db diabetic mice and that these effects are achieved at least in part by activating hepatic PPARα/γ and by inhibiting hepatic fatty acid synthase.