Proanthocyanidins regulate the Nrf2/ARE signaling pathway and protect neurons from cypermethrin-induced oxidative stress and apoptosis.

Cypermethrin, a type II pyrethroid pesticide, is one of the most widely used pesticides in agricultural and in household settings. The toxic effects of cypermethrin are a matter of concern, as humans are almost inevitably exposed to it in daily life. It is an urgent problem to seek natural substances from plants that can eliminate or relieve the effects of pesticide residues on human health. Proanthocyanidins are the most potent antioxidants and free radical scavengers in natural plants, and are widely available in fruits, vegetables, and seeds. We found that proanthocyanidins (1, 2.5, and 5 μg/mL) can decrease ROS generation, relieve mitochondrial membrane potential loss, repair nuclear morphology, reduce cell apoptosis, and protect neurons from cypermethrin-induced oxidative insult. The protective mechanism exerted by proanthocyanidins against cypermethrin-induced neurotoxicity is negatively regulate rather than activate the Nrf2/ARE signaling pathway to maintain intracellular homeostasis.