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Astragaloside IV ameliorates high glucose‑induced HK‑2 cell apoptosis and oxidative stress by regulating the Nrf2/ARE signaling pathway

  • Authors:
    • Jing Wang
    • Hong‑Min Guo
  • View Affiliations

  • Published online on: April 17, 2019     https://doi.org/10.3892/etm.2019.7495
  • Pages: 4409-4416
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Diabetic nephropathy (DN) has become the major cause of end‑stage renal disease increasing the mortality risk of diabetes. Research has demonstrated that the oxidative damage and apoptosis of renal tubular cells is present during DN. Astragaloside IV (AS‑IV) has been widely used for the treatment of many diseases, however, the role and mechanism by which AS‑IV may ameliorate high glucose‑induced apoptosis and oxidative stress of the human proximal tubular cell line HK‑2 remains largely unknown. The present study investigated the effect of AS‑IV on high glucose‑induced apoptosis and oxidative stress in HK‑2 cells. Cell viability, apoptosis and protein expression were detected by Trypan blue staining, Cell Counting Kit‑8 assay, terminal deoxynucleotidyl transferase 2'‑deoxyuridine‑5'‑triphosphate nick‑end labelling, flow cytometry and western blot analyses. In addition, enzymatic activities, including superoxide dismutase (SOD), glutathione peroxidase (GSH‑Px), catalase (CAT) and lipid peroxide (LPO), were measured with the corresponding detection kits. DCFH‑DA assay and flow cytometry were performed to detect the production of reactive oxygen species (ROS). Western blot analysis and reverse transcription‑quantitative polymerase chain reaction were conducted to evaluate protein and mRNA expressions of the nuclear factor erythroid 2 like 2 (Nrf2)/antioxidant response element (ARE) signaling pathway. The results demonstrated that AS‑IV significantly enhanced HK‑2 cell viability induced by high glucose in a dose‑dependent manner. In addition, AS‑IV notably inhibited HK‑2 cell apoptosis stimulated by high glucose, which may be associated with inhibition of BCL2 associated X protein, Cleaved‑caspase‑3 and Cleaved‑caspase‑9, expression and the promotion of Bcl‑2. AS‑IV significantly increased the activities of antioxidant enzymes SOD, GSH‑Px and CAT, and decreased the high‑glucose‑induced ROS production in HK‑2 cells, in a dose‑dependent manner. Finally, it was determined that AS‑IV regulated the Nrf2/ARE signaling pathway and inhibited the expression of liver‑type fatty acid binding protein. In conclusion, these findings may provide evidence that AS‑IV has a potential role for the treatment of DN.

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Copy and paste a formatted citation
APA
Wang, J., & Wang, J. (2019). Astragaloside IV ameliorates high glucose‑induced HK‑2 cell apoptosis and oxidative stress by regulating the Nrf2/ARE signaling pathway. Experimental and Therapeutic Medicine, 17, 4409-4416. https://doi.org/10.3892/etm.2019.7495
MLA
Wang, J., Guo, H."Astragaloside IV ameliorates high glucose‑induced HK‑2 cell apoptosis and oxidative stress by regulating the Nrf2/ARE signaling pathway". Experimental and Therapeutic Medicine 17.6 (2019): 4409-4416.
Chicago
Wang, J., Guo, H."Astragaloside IV ameliorates high glucose‑induced HK‑2 cell apoptosis and oxidative stress by regulating the Nrf2/ARE signaling pathway". Experimental and Therapeutic Medicine 17, no. 6 (2019): 4409-4416. https://doi.org/10.3892/etm.2019.7495