Rumman Mohammad, Pandey Shivani, Singh Babita, Gupta Mrinal, Mahdi Abbas Ali
Department of Biochemistry, King George's Medical University (KGMU), Lucknow, 226025, UP, India.
Metab Brain Dis. 2022 Oct;37(7):2521-2532. doi: 10.1007/s11011-022-01039-9. Epub 2022 Jul 27.
Genistein (GE) or 4',5,7-trihydroxyflavone, a plant derived isoflavone, is a biologically active compound having several beneficial properties. Studies showed that GE possesses anti-neoplastic, anti-tumor, anti-helminthic, anti-oxidant, and anti-inflammatory activities. Herein, we investigated the neuroprotective effects of GE in a mouse model of hypoxia-induced amnesia. Mice were exposed to hypoxic conditions (10% O2) in a designated hypoxia chamber and co-treated with GE (10, 20, or 30 mg/kg) for 4 weeks. Following this, behavioral tests were performed to evaluate memory performance. We assessed microglial activation in the hippocampus, amygdala, and pre-frontal cortex (PFC) regions by evaluating the Iba-1 and GFAP transcript levels, and MIP-1β, Cox-2, and IL6 protein levels. Apoptosis was assessed by evaluating Bax, BAD, and Bcl-2 mRNA levels, and caspase-3 activity. To uncover the underlying molecular mechanism, we evaluated the levels of Nrf2, HO-1, and NQO1 in different brain regions of mice from all groups. Results showed that hypoxia-exposed mice have reduced performance in the behavioral tests and GE treatment enhanced the memory performance in hypoxia-exposed mice. Moreover, hypoxia-exposed mice showed increased expression of microglial activation markers and enhanced apoptosis in the hippocampus, amygdala, and PFC. GE treatment suppressed microglial activation and prevented apoptosis in the brain of hypoxia-exposed mice. Furthermore, hypoxia-exposure reduced the expression of Nrf2, NQO1, and HO-1 while GE treatment ameliorated this decrease in different regions of hypoxia-exposed mice brain. In conclusion, GE prevents cognitive dysfunction by suppressing microglial activation and inhibiting apoptosis in the hypoxia-exposed mice brain.
金雀异黄素（GE），即4',5,7-三羟基黄酮，是一种源自植物的异黄酮，是一种具有多种有益特性的生物活性化合物。研究表明，GE具有抗肿瘤、抗寄生虫、抗氧化和抗炎活性。在此，我们研究了GE在缺氧诱导失忆小鼠模型中的神经保护作用。将小鼠置于指定的缺氧舱中暴露于缺氧条件（10%氧气）下，并与GE（10、20或30mg/kg）共同处理4周。此后，进行行为测试以评估记忆表现。我们通过评估Iba-1和GFAP转录水平以及MIP-1β、Cox-2和IL6蛋白水平，来评估海马体、杏仁核和前额叶皮质（PFC）区域的小胶质细胞活化情况。通过评估Bax、BAD和Bcl-2 mRNA水平以及caspase-3活性来评估细胞凋亡。为了揭示潜在的分子机制，我们评估了所有组小鼠不同脑区中Nrf2、HO-1和NQO1的水平。结果表明，暴露于缺氧环境的小鼠在行为测试中的表现下降，而GE处理增强了暴露于缺氧环境小鼠的记忆表现。此外，暴露于缺氧环境的小鼠在海马体、杏仁核和PFC中显示出小胶质细胞活化标志物的表达增加以及细胞凋亡增强。GE处理抑制了暴露于缺氧环境小鼠大脑中的小胶质细胞活化并预防了细胞凋亡。此外，缺氧暴露降低了Nrf2、NQO1和HO-1的表达，而GE处理改善了暴露于缺氧环境小鼠大脑不同区域的这种降低。总之，GE通过抑制暴露于缺氧环境小鼠大脑中的小胶质细胞活化和抑制细胞凋亡来预防认知功能障碍。
