Pongamol Prevents Neurotoxicity via the Activation of MAPKs/Nrf2 Signaling Pathway in H₂O₂-Induced Neuronal PC12 Cells and Prolongs the Lifespan of Caenorhabditis elegans

Despite tremendous advances in modern medicine, effective prevention or therapeutic strategies for age-related neurodegenerative diseases such as Alzheimer’s disease (AD) remain limited. Growing evidence now suggests that oxidative stress and apoptosis are increasingly associated with AD as promising therapeutic targets. Pongamol, a flavonoid, is the main constituent of pongamia pinnata and possesses a variety of pharmacological activities such as antioxidant, anti-aging and anti-inflammatory. In the present study, we investigated the antioxidant effects and mechanisms of pongamol in H₂O₂-induced PC12 cells and Caenorhabditis elegans (C. elegans). Our findings revealed that pongamol reduced cellular damage and apoptosis in H₂O₂-induced PC12 cells. Furthermore, pongamol reduced levels of apoptosis-related proteins Bax, Cyto C, Cleaved Caspase-3, and Cleaved PARP1, and increased the level of anti-apoptotic protein Bcl-2. Pongamol also effectively attenuated the level of oxidative stress markers such as glutathione (GSH) and reactive oxygen species (ROS) in H₂O₂-induced PC12 cells. Additionally, pongamol possessed antioxidant activity in H₂O₂-induced PC12 cells through the MAPKs/Nrf2 signaling pathway. Furthermore, pongamol exerted neuroprotective and anti-aging effects in C. elegans. All together, these results suggested that pongamol has a potential neuroprotective effect through the modulation of MAPKs/Nrf2 signaling pathway.