Further in vivo studies have also indicated that polydatin supplementation provided an antioxidant ability through the Sirt1/Nrf2/antioxidant-responsive element (ARE) signaling pathway to reduce diabetes-induced renal dysfunction [65], as well as through the Notch1/Hes1-Pten/Akt axis to improve ischemic/reperfusion-injured diabetic heart disease [66,67]. Here, HES1 is linked to diabetes mellitus.