Alleviates effects of γ-cyclodextrin/genistein inclusion complex on oxidative stress injury induced by organic hydrogen peroxide in PC12 cells via Nrf2/GPx4 signaling pathway

Genistein (GEN) is the most abundant aglycone in soy isoflavones and is a key factor distinguishing soybeans from other food sources. It holds significant nutritional value and exhibits notable biological activity. However, the low water solubility of genistein limits its widespread application. To improve its water solubility, this study prepared gamma-cyclodextrin (gamma-CD)/GEN inclusion complexes and investigated their mechanism of action in alleviating hydrogen peroxide-induced oxidative stress damage in PC12 cells. The results showed that gamma-CD/GEN could be uniformly and stably dispersed in the system. Cell experiments indicated that gamma-CD/GEN significantly increased cell survival after treatment with organic hydrogen peroxide, and promoted the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and the expression of glutathione peroxidase 4 (GPx4). It also improved mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) levels, thereby alleviating cell damage caused by oxidative stress. Further Nrf2 knockdown experiments revealed that gamma-CD/GEN failed to provide protection, and no protective effect was observed under RSL3 intervention. In conclusion, gamma-CD/ GEN exerts antioxidant effects by activating the Nrf2/GPx4 pathway, thereby reducing oxidative stress damage induced by organic hydrogen peroxide, providing a theoretical basis for the development of novel antioxidants.