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

  • Mol Neurobiol. 2024 Oct;61(10):8219-8233. doi: 10.1007/s12035-024-04110-x.
Shaojun Wu  1 ,  Jie Miao  1 ,  Susu Zhu  1 ,  Xinyuan Wu  1 ,  Jindan Shi  1 ,  Jichao Zhou  1 ,  Yi Xing  1 ,  Kun Hu  1 ,  Jie Ren  2 ,  Hao Yang  3
Affiliations
  • 1. School of Pharmacy, Changzhou University, No. 1. Gehu Middle Road, Changzhou, 213164, Jiangsu, China.
  • 2. School of Pharmacy, Changzhou University, No. 1. Gehu Middle Road, Changzhou, 213164, Jiangsu, China. [email protected].
  • 3. Department of Pharmacy, the Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, No. 68. Gehu Middle Road, Changzhou, 213164, Jiangsu, China. [email protected].
PMID: 38483657 DOI: 10.1007/s12035-024-04110-x
Abstract

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.

Keywords
Alzheimer’s disease; Apoptosis; MAPKs/Nrf2 signaling pathway; Oxidative stress; Pongamol.
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