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葛根中刺芒柄花素预防和改善阿尔兹海默病的机制

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随着全球人口老龄化,阿尔兹海默病(Alzheimer's Disease,AD)患者的数量迅速增加.葛根具有悠久的食用和药用历史与价值,其成分可在AD的病情发展中起到预防或辅助改善病情的作用.本研究首先通过网络药理学和分子对接,筛选出葛根中可能作用于AD的成分,刺芒柄花素(formononetin,FMN).然后,通过使用amyloid-β 42(Aβ42)处理的SH-SY5Y细胞和表达Aβ42的转基因秀丽隐杆线虫CL2120分别作为AD细胞和动物模型,探索FMN对AD的作用.结果表明,Aβ42导致细胞中的促凋亡因子BAX上升,抑制凋亡的BCL-2下降,导致BAX/BCL-2下游的凋亡因子Caspase-3上升,而加入FMN可以逆转这一过程.同时,FMN抑制了ROS和MDA的产生,增强了抗氧化SOD的活性,并稳定了线粒体膜,由此减少了细胞凋亡.此外,FMN降低了线虫CL2120的氧化应激,并抑制了Aβ42在其体内的聚集,从而延长了它们的寿命.这些发现表明FMN可能对AD具有一定的预防和改善作用.
Mechanism investigation of Pueraria-extracted formononetin on Alzheimer's Disease
The number of people with Alzheimer's Disease(AD)has increased quickly with the aging popu-lation worldwide.Extracts from Pueraria lobata,which has a long history of eating and treating diseases,may provide more reliable and safer treatments for ameliorating disease progression of AD.In this study,network pharmacology and molecular docking were used to screen from Pueraria lobata to find potential therapeutic substance on AD,formononetin(FMN).Next,Aβ42-treated cells and Aβ42-expressed C.ele-gans CL2120 were used to explore the effects of FMN on AD in vitro and in vivo,respectively.The results showed that FMN reversed the increased ratio of BAX/BCL-2,leading to the down-regulation of pro-in-flammatory cytokines,including Caspase-3 that cause neuronal death in AD.Moreover,FMN inhibited the production of ROS and MDA,enhanced the activities of the antioxidant SOD and stabilized the mitochon-drial membrane.Thereby FMN reduced the apoptosis of Aβ42-treated cells.Besides,FMN reduced oxida-tive stress and inhibited Aβ42-accumulation in C.elegans CL2120,resulting in extending their lifespans.These findings suggested that FMN may provide potential neuroprotective effects on AD.

Alzheimer's diseaseamyloid-β 42formononetinBAX/BCL-2 pathwayoxidative stress

刘其羽、邹一峰、黎阳

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武汉轻工大学生命科学与技术学院,武汉 430023

阿尔兹海默病 β-淀粉样蛋白42 刺芒柄花素 BAX/BCL-2通路 氧化应激

2024

武汉轻工大学学报
武汉工业学院

武汉轻工大学学报

影响因子:0.356
ISSN:1009-4881
年,卷(期):2024.43(4)