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Safflower yellow B suppresses HepG2 cell injury induced by oxidative stress through the AKT/Nrf2 pathway

  • Authors:
    • Zhongying Ma
    • Caixia Li
    • Yi Qiao
    • Chengtao Lu
    • Jiankang Li
    • Wei Song
    • Jin Sun
    • Xiaohu Zhai
    • Jing Niu
    • Qian Ren
    • Aidong Wen
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
    Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 603-612
    |
    Published online on: January 21, 2016
       https://doi.org/10.3892/ijmm.2016.2462
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Abstract

Oxidative stress plays an important role in the pathogenesis of various liver diseases. Safflower yellow B (SYB) has been reported to protect the brain against damage induced by oxidative stress; however, whether SYB can also protect hepatocytes from oxidative stress remains unknown. In the present study, to determine whether pre-treatment with SYB reduces hydrogen peroxide (H2O2)‑induced oxidative stress in HepG2 cells, we investigated H2O2-induced oxidative damage to HepG2 cells treated with or without SYB. Cell viability was measured by MTT assay and cytotoxicity was evaluated by lactate dehydrogenase (LDH) assay. The activities of the antioxidant enzymes, glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were determined using respective kits. Intracellular reactive oxygen species (ROS) accumulation in the HepG2 cells was monitored using the fluorescent marker, 2',7'-dichlorodihydrofluorescein diacetate (H2DCF-DA). Cell apoptosis was evaluated by determining the activity of caspase-3 and by Annexin V/propidium iodide (PI) double staining. Protein expression levels were measured by western blot analysis, and the levels of related cellular kinases were also determined. H2O2 induced pronounced injury to the HepG2 cells, as evidenced by increased levels of malondialdehyde (MDA) and ROS, the decreased activity of SOD and GSH-Px, the increased activitation of caspase-3 and cell apoptosis, and the loss of mitochondrial membrane potential. SYB significantly inhibited the damaging effects of H2O2, indicating that it protected the cells against H2O2-induced oxidative damage. Moreover, pre-treatment with SYB increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1) and NAD(P)H dehydrogenase, quinone 1 (NQO1) which are peroxiredoxins. SYB also significantly increased the phosphorylation of AKT. However, this inductive effect was blunted in the presence of the AKT inhibitor, LY294002. The findings of our study suggest that the activation of the AKT/Nrf2 pathway is involved in the cytoprotective effects of SYB against oxidative stress. Our findings provide new insight into the cytoprotective effects of SYB and the possible mechanisms underlying these effects. Thus, SYB may prove to be of therapeutic value for the treatment of various liver diseases.
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Copy and paste a formatted citation
Spandidos Publications style
Ma Z, Li C, Qiao Y, Lu C, Li J, Song W, Sun J, Zhai X, Niu J, Ren Q, Ren Q, et al: Safflower yellow B suppresses HepG2 cell injury induced by oxidative stress through the AKT/Nrf2 pathway. Int J Mol Med 37: 603-612, 2016.
APA
Ma, Z., Li, C., Qiao, Y., Lu, C., Li, J., Song, W. ... Wen, A. (2016). Safflower yellow B suppresses HepG2 cell injury induced by oxidative stress through the AKT/Nrf2 pathway. International Journal of Molecular Medicine, 37, 603-612. https://doi.org/10.3892/ijmm.2016.2462
MLA
Ma, Z., Li, C., Qiao, Y., Lu, C., Li, J., Song, W., Sun, J., Zhai, X., Niu, J., Ren, Q., Wen, A."Safflower yellow B suppresses HepG2 cell injury induced by oxidative stress through the AKT/Nrf2 pathway". International Journal of Molecular Medicine 37.3 (2016): 603-612.
Chicago
Ma, Z., Li, C., Qiao, Y., Lu, C., Li, J., Song, W., Sun, J., Zhai, X., Niu, J., Ren, Q., Wen, A."Safflower yellow B suppresses HepG2 cell injury induced by oxidative stress through the AKT/Nrf2 pathway". International Journal of Molecular Medicine 37, no. 3 (2016): 603-612. https://doi.org/10.3892/ijmm.2016.2462
Copy and paste a formatted citation
x
Spandidos Publications style
Ma Z, Li C, Qiao Y, Lu C, Li J, Song W, Sun J, Zhai X, Niu J, Ren Q, Ren Q, et al: Safflower yellow B suppresses HepG2 cell injury induced by oxidative stress through the AKT/Nrf2 pathway. Int J Mol Med 37: 603-612, 2016.
APA
Ma, Z., Li, C., Qiao, Y., Lu, C., Li, J., Song, W. ... Wen, A. (2016). Safflower yellow B suppresses HepG2 cell injury induced by oxidative stress through the AKT/Nrf2 pathway. International Journal of Molecular Medicine, 37, 603-612. https://doi.org/10.3892/ijmm.2016.2462
MLA
Ma, Z., Li, C., Qiao, Y., Lu, C., Li, J., Song, W., Sun, J., Zhai, X., Niu, J., Ren, Q., Wen, A."Safflower yellow B suppresses HepG2 cell injury induced by oxidative stress through the AKT/Nrf2 pathway". International Journal of Molecular Medicine 37.3 (2016): 603-612.
Chicago
Ma, Z., Li, C., Qiao, Y., Lu, C., Li, J., Song, W., Sun, J., Zhai, X., Niu, J., Ren, Q., Wen, A."Safflower yellow B suppresses HepG2 cell injury induced by oxidative stress through the AKT/Nrf2 pathway". International Journal of Molecular Medicine 37, no. 3 (2016): 603-612. https://doi.org/10.3892/ijmm.2016.2462
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