Daidzein protects endothelial cells against high glucose-induced injury through the dual-activation of PPARα and PPARγ

Endothelial damage caused by persistent glucose and lipid metabolism disorders is the main reason of diabetic vascular diseases. Daidzein exerts positive effects on vascular dysfunction. Peroxisome proliferator-activated receptors (PPARs) regulate critically glucose and lipid metabolism. However, the interaction of daidzein to PPARs is still insufficiently explored. In this study, the cell proliferation was detected by EdU. The intrinsic activity and binding affinity of daidzein for human PPARs (hPPARs) were estimated by transactivation reporter gene test and HPLC-UV method, respectively. Daidzein significantly reversed high glucose (HG, at 30 mmol/l)-induced injury in HUVECs, which was inhibited by both PPAR alpha and PPAR gamma antagonist, but no PPAR beta antagonist. Daidzein selectively activated hPPAR alpha and hPPAR gamma 1 , but weakly hPPAR beta. Additionally, daidzein also bound to both hPPAR alpha and hPPAR gamma 1 . The findings suggested that daidzein may be a PPAR alpha and PPAR gamma dual-agonist. The amelioration of daidzein on HUVECs from hyperglycemia may be mediated by the activation of PPAR alpha and PPAR gamma receptors.