Baicalein Alleviates Liver Oxidative Stress and Apoptosis Induced by High-Level Glucose through the Activation of the PERK/Nrf2 Signaling Pathway
| Autor: | Yan Xing, Yongbin Xu, Chunshan Quan, Wenlong Sun, Yuesheng Dong, Jin Sun |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
baicalein NF-E2-Related Factor 2 Pharmaceutical Science liver medicine.disease_cause Article Antioxidants Diabetes Mellitus Experimental Analytical Chemistry lcsh:QD241-441 Mice eIF-2 Kinase 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine lcsh:Organic chemistry Downregulation and upregulation Drug Discovery medicine Animals Humans oxidative stress Physical and Theoretical Chemistry Protein kinase A 030304 developmental biology 0303 health sciences Kinase Endoplasmic reticulum Organic Chemistry apoptosis Subcellular localization Baicalein Cell biology Glucose Diabetes Mellitus Type 2 chemistry PERK/Nrf2 signaling pathway Chemistry (miscellaneous) Apoptosis Sweetening Agents 030220 oncology & carcinogenesis Flavanones diabetes mellitus Molecular Medicine Oxidative stress |
| Zdroj: | Molecules Volume 25 Issue 3 Molecules, Vol 25, Iss 3, p 599 (2020) |
| ISSN: | 1420-3049 |
| DOI: | 10.3390/molecules25030599 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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