Hispolon alleviates oxidative damage by stimulating the Nrf2 signaling pathway in PC12 cells

Natural products derived from the daily diet are garnering increasing attention for neurodegenerative disease (ND) treatment. Hispolon (His), a small molecule from Phellinus linteus, has been reported to have various pharmacological activities. Here, we evaluated its protective effect on a neuron-like rat pheochromocytoma cell line (PC12). Results showed that His could restore cell death induced by oxidative damage. Nuclear factor-erythroid 2 (NF-E2)-related factor 2 (Nrf2) plays a significant role in maintaining cellular redox homeostasis. After treatment with His, some Nrf2-governed antioxidant genes were upregulated in a dose-dependent manner. However, the protective effect of His on PC12 cells was easily terminated by Nrf2 knockdown, demonstrating that Nrf2 is a critical component in this cytoprotective process. Taken together, our study showed that His was not only an effective activator of Nrf2 but also a promising candidate for ND treatment.