TITLE:
The Dietary Polyphenol Isorhapontigenin Activates Nrf2 via Targeting AKT to Exert Antioxidant and Anti-Ferroptotic Effects in SH-SY5Y Cells
AUTHORS:
Yichen Wang, Wenze Wu, Yue Hou
KEYWORDS:
Isorhapontigenin, Neuroprotection, Dietary Polyphenol, AKT, Nrf2
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.14 No.2,
February
28,
2026
ABSTRACT: Isorhapontigenin (ISO) is a natural polyphenol found in grapes and several common Chinese medicinal herbs. As an analog of resveratrol, it exhibits a wide spectrum of biological activities. Notably, ISO has been reported to possess neuroprotective effects, although the underlying mechanisms remain incompletely understood. Oxidative stress and ferroptosis are key pathological processes leading to neuronal damage in neurological disorders. In this study, we used an oxygen-glucose deprivation/reoxygenation (OGD/R)-induced SH-SY5Y cell model to investigate the neuroprotective effects of ISO. We examined its ability to alleviate oxidative stress and inhibit ferroptosis, and further explored the potential molecular mechanisms. This study found that ISO exerts antioxidant and anti-ferroptotic effects by targeting AKT to activate Nrf2. The results of this study aim to provide experimental evidence supporting the development of ISO as a functional food ingredient for neuroprotection.