Gentiopicroside Ameliorates Oxidative Stress and Lipid Accumulation through Nuclear Factor Erythroid 2-Related Factor 2 Activation
Joint Authors
Jin, Meiyu
Wang, Yue
Yan, Siru
Shen, Bingyu
Li, Zheng
Qin, Haiyan
Wang, Qi
Li, Jinxia
Liu, Guowen
Feng, Haihua
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-06-17
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
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 (PPARα), 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, PPARα, 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 PPARα 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.
American Psychological Association (APA)
Jin, Meiyu& Feng, Haihua& Wang, Yue& Yan, Siru& Shen, Bingyu& Li, Zheng…[et al.]. 2020. Gentiopicroside Ameliorates Oxidative Stress and Lipid Accumulation through Nuclear Factor Erythroid 2-Related Factor 2 Activation. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-13.
https://search.emarefa.net/detail/BIM-1204081
Modern Language Association (MLA)
Jin, Meiyu…[et al.]. Gentiopicroside Ameliorates Oxidative Stress and Lipid Accumulation through Nuclear Factor Erythroid 2-Related Factor 2 Activation. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-13.
https://search.emarefa.net/detail/BIM-1204081
American Medical Association (AMA)
Jin, Meiyu& Feng, Haihua& Wang, Yue& Yan, Siru& Shen, Bingyu& Li, Zheng…[et al.]. Gentiopicroside Ameliorates Oxidative Stress and Lipid Accumulation through Nuclear Factor Erythroid 2-Related Factor 2 Activation. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-13.
https://search.emarefa.net/detail/BIM-1204081
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1204081