Genistein: mechanisms of action for a pleiotropic neuroprotective agent in stroke

Genistein is a plant estrogen promoted as an alternative to post-menopausal hormone therapy because of a good safety profile and its promotion as a natural product. Several preclinical studies of cerebral ischemia and other models of brain injury support a beneficial role for genistein in protecting the brain from injury whether administered chronically or acutely. Like estrogen, genistein is a pleiotropic molecule that engages several different mechanisms to enhance brain health, including reduction of oxidative stress, promotion of growth factor signaling, and immune suppression. These actions occur in endothelial, glial, and neuronal cells to provide a coordinated beneficial action to ischemic challenge. Though many of these protective actions are associated with estrogen-like actions of genistein, additional activities on other receptors and intracellular targets suggest that genistein is more than a mere estrogen-mimic. Importantly, genistein lacks some of the detrimental effects associated with post-menopausal estrogen treatment and may provide an alternative to hormone therapy in those patients at risk for ischemic events.