二甲双胍
甲基乙二醛
神经保护
化学
细胞凋亡
药理学
类黄酮
生物化学
抗氧化剂
糖尿病
生物
内分泌学
酶
作者
Danyang Zhang,Xiaoshi He,Ting Wang,Yan Xing,Zhilong Xiu,Yongming Bao,Yuesheng Dong
出处
期刊:Molecules
[MDPI AG]
日期:2024-05-14
卷期号:29 (10): 2306-2306
标识
DOI:10.3390/molecules29102306
摘要
Methylglyoxal-induced ROS elevation is the primary cause of neuronal damage. Metformin is a traditional hypoglycemic drug that has been reported to be beneficial to the nervous system. In this study, flavonoids were found to enhance the protective effect of metformin when added at a molar concentration of 0.5%. The structure–activity relationship (SAR) analysis indicated that ortho- substitution in the B ring, and the absence of double bonds between the 2 and 3 position combined with the gallate substitution with R configuration at the 3 position in the C ring played crucial roles in the synergistic effects, which could be beneficial for designing a combination of the compounds. Additionally, the mechanism study revealed that a typical flavonoid, EGCG, enhanced ROS scavenging and anti-apoptotic ability via the BCL2/Bax/Cyto C/Caspase-3 pathway, and synergistically inhibited the expression of GSK-3β, BACE-1, and APP in PC-12 cells when used in combination with metformin. The dose of metformin used in the combination was only 1/4 of the conventional dose when used alone. These results suggested that ROS-mediated apoptosis and the pathways related to amyloid plaques (Aβ) formation can be the targets for the synergistic neuroprotective effects of flavonoids and metformin.
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