Genistein Prevents Hypoxia-Induced Cognitive Dysfunctions by Ameliorating Oxidative Stress and Inflammation in the Hippocampus.

Genistein (GE), a plant-derived isoflavone, is a polyphenolic non-steroidal compound. Studies showed that GE possesses anti-cancer, anti-inflammatory, anti-microbial, anti-oxidant, and anti-apoptotic activities. However, the neuroprotective role of GE in amnesia has not been studied. This study aimed to evaluate the anti-amnesic potential of GE in a mice model of hypoxia-induced amnesia and to understand the underlying mechanism. Mice were exposed to hypoxia (10% O2) and administered vehicle or GE (10, 20, 30 mg/kg) orally for 28 days. Thereafter, Morris water maze (MWM), novel object recognition (NOR), and passive avoidance task (PAT) were performed to evaluate cognitive behavior. Next, we performed biochemical tests and gene expression analysis to uncover the mechanism underlying GE mode of action. Our results showed that GE-treatment ameliorated hypoxia-induced cognitive dysfunctions in mice. Further, GE-treatment suppressed the oxidative stress in the hippocampus of amnesic mice as evidenced by reduced lipid peroxidation, reduced nitrite and ROS levels, and increased levels of reduced glutathione (GSH) and increased total antioxidant capacity. GE treatment reduced the expression of pro-inflammatory cytokines TNFα, IL1β, IL6, and MCP-1 and increased the expression of anti-inflammatory cytokine IL10 in the hippocampus of amnesic mice. Finally, GE treatment enhanced the expression of neuroprotective genes including BDNF, CREB, CBP, and IGF1 in the hippocampus of amnesic mice. Altogether, our results showed that GE treatment prevents hypoxia-induced cognitive dysfunction in mice by reducing oxidative stress and suppressing neuroinflammation while increasing the expression of neuroprotective genes in the hippocampus.