Abstract

Cadmium (Cd) is a highly neurotoxic environmental pollutant. Puerarin (Pur) is a natural antioxidant isolated from Kudzu root that exhibits a powerful neuroprotective effect. Herein, we illustrated the mechanism underlying the protective effect of Pur on Cd-induced rat neurocyte injury in an in vivo rat model as well as in vitro using PC12 cells and primary rat cerebral cortical neurons. First, the results showed that Pur alleviated Cd-induced cerebral cortical pathological damage and decreased the viability of neurocytes. Furthermore, Cd activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, which plays a negative role in Cd-induced rat neurocyte injury. In addition, Pur alleviated Cd-induced oxidative stress by enhancing antioxidant defense, reducing reactive oxygen species (ROS) accumulation and lipid peroxidation, and inhibiting activation of the Nrf2 signaling pathway in rat neurocytes. Moreover, Pur inhibited the Cd-induced mitochondrial unfolded protein response (UPRmt) in rat neurocytes. Overall, Pur alleviated Cd-induced rat neurocyte injury by alleviating Nrf2-mediated oxidative stress and inhibiting UPRmt.