1. Gentiopicroside Ameliorates Oxidative Stress and Lipid Accumulation through Nuclear Factor Erythroid 2-Related Factor 2 Activation.
- Author
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Jin M, Feng H, Wang Y, Yan S, Shen B, Li Z, Qin H, Wang Q, Li J, and Liu G
- Subjects
- Animals, Antioxidants metabolism, Cell Survival drug effects, Disease Models, Animal, Fatty Acids, Nonesterified metabolism, Fatty Acids, Nonesterified pharmacology, Hep G2 Cells, Humans, Hyperlipidemias drug therapy, Hyperlipidemias metabolism, Hyperlipidemias pathology, Lipogenesis drug effects, Mice, NF-E2-Related Factor 2 genetics, Non-alcoholic Fatty Liver Disease drug therapy, Non-alcoholic Fatty Liver Disease metabolism, Non-alcoholic Fatty Liver Disease pathology, PPAR alpha metabolism, Signal Transduction drug effects, Antioxidants pharmacology, Iridoid Glucosides pharmacology, Lipid Metabolism drug effects, NF-E2-Related Factor 2 metabolism, Oxidative Stress drug effects
- Abstract
The activation of nuclear factor erythroid 2-related factor 2 (Nrf2) is closely related to the alleviation of nonalcoholic fatty liver disease (NAFLD) by regulating oxidative stress and lipid homeostasis. Gentiopicroside (GPS), an iridoid glycoside found in the Gentianaceae, possesses anti-inflammatory and antioxidant effects. However, the protective effects of GPS on lipid accumulation and oxidative damage have not been investigated thoroughly in free fatty acid- (FFA-) induced HepG2 cells and tyloxapol- (Ty-) induced hyperlipidemia mice. Cell counting kit-8 assays, Oil Red O staining, Western blotting analysis, extraction of nuclear and cytosolic proteins, and biochemical index assay were employed to explore the mechanisms by which GPS exerts a protective effect on FFA-induced HepG2 cells and Ty-induced hyperlipidemia mouse model. This paper demonstrates that GPS could effectively alleviate NAFLD by elevating cell viability, reducing fatty deposition, downregulating TG, and activating nucleus Nrf2 in FFA-induced HepG2 cells. Meanwhile, GPS significantly regulated the activation of phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway, Nrf2 antioxidant pathway, peroxisome proliferator-activated receptor α (PPAR α ), and GPS-inhibited sterol regulatory element-binding protein-1c (SREBP-1c) expression in FFA-stimulated lipid accumulation of HepG2 cells and Ty-treated mice. Interestingly, we highlight that PI3K/AKT inhibitor (LY294002) markedly increased the expression of Nrf2 antioxidant pathway, PPAR α , and downregulated SREBP-1c in FFA-stimulated HepG2 cells. For these reasons, we found that the deletion of Nrf2 could lose the protective effects of GPS on the Nrf2 antioxidant pathway and PPAR α activation and SREBP-1c inactivation in FFA-stimulated HepG2 cells and Ty-treated mice. GPS treatment had no effect on abnormal lipogenesis and antioxidant enzymes in Ty-induced Nrf2
-/- mice. This work gives a new explanation that GPS may be a useful therapeutic strategy for NAFLD through upregulation of the Nrf2 antioxidant pathway, which can alleviate oxidative damage and lipid accumulation., Competing Interests: Meiyu Jin, Haihua Feng, Yue Wang, Siru Yan, Bingyu Shen, Zheng Li, Haiyan Qin, Qi Wang, Jinxia Li, and Guowen Liu declare that they have no conflicts of interest., (Copyright © 2020 Meiyu Jin et al.)- Published
- 2020
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