School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China.
School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China; Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, China; Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, China.
J Nutr Biochem. 2022 Nov;109:109118. doi: 10.1016/j.jnutbio.2022.109118. Epub 2022 Aug 3.
Genistein (GS), an isoflavone compound found in soybean, plays a neuroprotective role in Alzheimer's disease (AD). However, the mechanism of its action remains unclear. Herein, binding ability between GS and GRP78 was predicted by molecular docking, and the effect of GS in vivo and vitro were further studied. In this study, the effects of GS on learning and memory ability, changes of hippocampal neurons and ultrastructure of hippocampal CA3 region in AD rats were investigated. Besides, the protein or mRNA levels of the related proteins were detected. The results showed GS could effectively improve the learning and the memory ability, reduce the damage of hippocampal neurons, and decrease the protein or mRNA expression levels of GRP78, CHOP, Caspase-12, Cle-Caspase-9, Cle-Caspase-3, PERK, and p-PERK. Taken together, our data reveal GS has a neuroprotective effect by inhibiting the ERS-mediated apoptotic pathway, which may be a new therapeutic target for the treatment of AD.
染料木黄酮（GS）是大豆中发现的一种异黄酮化合物，在阿尔茨海默病（AD）中发挥神经保护作用。然而，其作用机制尚不清楚。本文通过分子对接预测了 GS 与 GRP78 的结合能力，并进一步研究了 GS 在体内和体外的作用。本研究探讨了 GS 对 AD 大鼠学习记忆能力、海马神经元变化及海马 CA3 区超微结构的影响，并检测了相关蛋白的蛋白或 mRNA 水平。结果表明，GS 能有效改善学习记忆能力，减轻海马神经元损伤，降低 GRP78、CHOP、Caspase-12、Cle-Caspase-9、Cle-Caspase-3、PERK 和 p-PERK 的蛋白或 mRNA 表达水平。综上所述，我们的数据表明，GS 通过抑制 ERS 介导的细胞凋亡途径发挥神经保护作用，这可能为 AD 的治疗提供新的治疗靶点。
