Neuroprotective effects of genistein-3′-sodium sulfonate on focal cerebral ischemia in rats

•We sulfonated genistein to synthesize a relatively more water-soluble compound to improve its poor bioavailability, namely genistein-3′-sodium sulfonate (GSS).•The neuroprotective effect of GSS in vitro and in vivo is further confirmed.•The increased Bcl-2/Bax expression ratio and reduced Caspase 3 activity may mediate the neuroprotection of GSS. In order to improve the poor water solubility of genistein (4′,5,7-trihydroxyisoflavone), which is extracted from food sources such as tofu, soybeans, and kudzu, we sulfonated genistein to synthesize a relatively more water-soluble compound, namely genistein-3′-sodium sulfonate (GSS). Our previous studies demonstrate that GSS protects cortical neurons from injury induced by focal cerebral ischemia. However, the molecular mechanisms underlying this protective effect remain unclear. We aimed to investigate the protective effect and potential molecular mechanisms of action of GSS in rat glutamate-induced cortical neuron injury in vitro and middle cerebral artery occlusion (MCAO) in vivo models. Our results showed that GSS exhibited a protective effect against glutamate-induced cytotoxicity in rat cortical neurons by reducing lactate dehydrogenase (LDH) release, inhibiting cell apoptosis, increasing Bcl-2/Bax expression ratio, and reducing Caspase 3 activity. GSS also decreased the infarcted area and neurological deficits in the rat MCAO model, reduced LDH release from the brain tissue to the serum, increased the Bcl-2/Bax expression ratio, and reduced Caspase 3 activity. These findings suggest that GSS protects rat cortical neurons from injury induced by focal cerebral ischemia in both in vitro and in vivo models, through increased Bcl-2/Bax expression ratio and reduced Caspase 3 activity.