NOS3 and Cerebral ischemia: For example, genistein, a natural phytoestrogen, enhances the thiol modification of Keap1 by NO through increasing the activation of endothelial NOS (eNOS), ensuing to upregulates Nrf2/HO-1 antioxidant signaling pathway, and finally exerting a protective effect on delayed neuronal cell death and cognitive decline in the hippocampal CA1 region due to cerebral ischemia (Wang et al., 2013).