甲基乙二醛
氧化应激
化学
神经母细胞瘤
药理学
氧化磷酸化
结构-活动关系
生物化学
细胞生物学
医学
生物
细胞培养
体外
遗传学
酶
作者
Danyang Zhang,Xia Li,Xiaoshi He,Yan Xing,Bo Jiang,Zhilong Xiu,Yongming Bao,Zhilong Xiu
出处
期刊:Molecules
[MDPI AG]
日期:2022-11-12
卷期号:27 (22): 7804-7804
标识
DOI:10.3390/molecules27227804
摘要
Methylglyoxal-induced oxidative stress and cytotoxicity are the main factors causing neuronal death-related, diabetically induced memory impairment. Antioxidant and anti-apoptotic therapy are potential intervention strategies. In this study, 25 flavonoids with different substructures were assayed for protecting PC-12 cells from methylglyoxal-induced damage. A structure-activity relationship (SAR) analysis indicated that the absence of the double bond at C-2 and C-3, substitutions of the gallate group at the 3 position, the pyrogallol group at the B-ring, and the R configuration of the 3 position enhanced the protection of flavan-3-ols, and a hydroxyl substitution at the 4' and meta-positions were important for the protection of flavonol. These SARs were further confirmed by molecular docking using the active site of the Keap1-Nrf2 complex as the receptor. The mechanistic study demonstrated that EGCG with the lowest EC50 protected the PC-12 cells from methylglyoxal-induced damage by reducing oxidative stress via the Nrf2/Keap1/HO-1 and Bcl-2/Bax signaling pathways. These results suggested that flavan-3-ols might be a potential dietary supplement for protection against diabetic encephalopathy.
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