Baicalein Alleviates Liver Oxidative Stress and Apoptosis Induced by High-Level Glucose through the Activation of the PERK/Nrf2 Signaling Pathway

被引:49
作者
Dong, Yuesheng [1 ]
Xing, Yan [1 ]
Sun, Jin [1 ]
Sun, Wenlong [1 ,2 ]
Xu, Yongbin [3 ,4 ]
Quan, Chunshan [3 ,4 ]
机构
[1] Dalian Univ Technol, Sch Bioengn, Dalian 116024, Peoples R China
[2] Shandong Univ Technol, Shandong Prov Res Ctr Bioinformat Engn & Tech, Sch Life Sci, Zibo 255049, Peoples R China
[3] Dalian Minzu Univ, Key Lab Biotechnol & Bioresources Utilizat, Minist Educ, Dalian 116024, Peoples R China
[4] Dalian Minzu Univ, Coll Life Sci, Dept Bioengn, Dalian 116600, Peoples R China
来源
MOLECULES | 2020年 / 25卷 / 03期
基金
中国国家自然科学基金;
关键词
diabetes mellitus; baicalein; oxidative stress; apoptosis; liver; PERK/Nrf2 signaling pathway; INSULIN-RESISTANCE; ER STRESS; FLAVONOIDS; ACARBOSE; ANTIOXIDANT; STREPTOZOTOCIN; MECHANISMS; INDUCTION; PROTECTS; IMPROVES;
D O I
10.3390/molecules25030599
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Baicalein, a widely-distributed natural flavonoid, exhibits antioxidative activity in mice with type-2 diabetes. However, the underlying mechanisms remain partially elucidated. In this study, we investigated the effect of baicalein on protein kinase R-like ER kinase (PERK)/nuclear factor erythroid-2-related factor 2 (Nrf2) pathway for the alleviation of oxidative stress and apoptosis. Human liver HL-7702 cells were stimulated with 60.5 mM of glucose to induce oxidative stress and treated with baicalein. The apoptosis was determined by fluorescence microscopy and flow cytometry. The regulation of the PERK/Nrf2 pathway by baicalein was determined by immunoblotting in both HL-7702 cells and liver tissues from diabetic mice. We found that baicalein significantly alleviated the oxidative stress and apoptosis in HL-7702 cells stimulated with glucose. Mechanistic studies showed that baicalein downregulated PERK and upregulated Nrf2, two key proteins involved in endoplasmic reticulum stress, in both HL-7702 cells and liver tissues from diabetic mice receiving baicalein treatment. Furthermore, the subcellular localization of Nrf2 and the regulation of downstream proteins including heme oxygenase-1 and CCAAT-enhancer-binding protein homologous protein (CHOP) by baicalein were also investigated. Our results suggest that the regulation of the PERK/Nrf2 pathway is one of the mechanisms contributing to the bioactivities of baicalein to improve diabetes-associated complications.
引用
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页数:17
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