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Pinocembrin ameliorates lipopolysaccharide‑induced HK‑2 cell apoptosis and inflammation by regulating endoplasmic reticulum stress

  • Authors:
    • Yu Zhang
    • Chenxi Yu
    • Yi Feng
  • View Affiliations / Copyright

    Affiliations: Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200082, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 513
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    Published online on: June 14, 2022
       https://doi.org/10.3892/etm.2022.11440
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Abstract

Pinocembrin (PINO) is a natural flavonoid drug that possesses a range of biological activities, including antimicrobial, antioxidant and anti‑inflammatory activities. The specific aim of the present study was to examine the pharmacological role of PINO in sepsis‑mediated acute kidney injury (AKI), as well as to investigate the potential underlying mechanism. Human renal tubular epithelial cells (of the HK‑2 cell line) were stimulated with lipopolysaccharide (LPS) for 24 h to simulate septic AKI in vitro, after which the experiments were repeated and the cells were pretreated with increasing concentrations of PINO (0, 50, 100 and 200 µg/ml). Using an MTT cell viability assay, PINO was revealed to be non‑toxic to HK‑2 cells. In LPS‑treated HK‑2 cells, PINO alleviated the loss of cell viability. Western blotting was used to analyze the expression levels of pro‑inflammatory cytokines, including IL‑1β, IL‑6 and TNF‑α, and the results revealed that PINO decreased the expression levels of these cytokines in a concentration‑dependent manner. Furthermore, malondialdehyde (MDA) and glutathione (GSH) activities were assessed using MDA and GSH assay kits and it was revealed that PINO decreased the significantly increased level of malondialdehyde, while it also decreased the reduction in the level of GSH in LPS‑challenged HK‑2 cells. In addition, a TUNEL assay and western blotting were performed to examine cell apoptosis, and PINO was identified to significantly inhibit the level of apoptosis in LPS‑induced HK‑2 cells. Subsequently, the expression levels of endoplasmic reticulum stress (ERS)‑associated factors, including activating transcription factor 4, C/EBP homologous protein and phosphorylated/total eukaryotic translation initiation factor 2 subunit 1 were examined by western blotting and it was demonstrated that ERS was triggered in HK‑2 cells exposed to LPS, although this was partly circumvented through PINO treatment in a concentration‑dependent manner. Furthermore, after the addition of tunicamycin, which acts as an agonist of ERS, the aforementioned experiments were performed again. Tunicamycin led to partial abolition of the protective function of PINO against inflammation, oxidative stress and apoptosis in LPS‑challenged HK‑2 cells. Overall, the results of the present study demonstrated that PINO was able to ameliorate the injuries sustained by LPS‑challenged HK‑2 cells via modulating ERS to reduce inflammation, oxidative stress and apoptosis; therefore, PINO may be a novel candidate drug for treating septic AKI.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang Y, Yu C and Feng Y: Pinocembrin ameliorates lipopolysaccharide‑induced HK‑2 cell apoptosis and inflammation by regulating endoplasmic reticulum stress. Exp Ther Med 24: 513, 2022.
APA
Zhang, Y., Yu, C., & Feng, Y. (2022). Pinocembrin ameliorates lipopolysaccharide‑induced HK‑2 cell apoptosis and inflammation by regulating endoplasmic reticulum stress. Experimental and Therapeutic Medicine, 24, 513. https://doi.org/10.3892/etm.2022.11440
MLA
Zhang, Y., Yu, C., Feng, Y."Pinocembrin ameliorates lipopolysaccharide‑induced HK‑2 cell apoptosis and inflammation by regulating endoplasmic reticulum stress". Experimental and Therapeutic Medicine 24.2 (2022): 513.
Chicago
Zhang, Y., Yu, C., Feng, Y."Pinocembrin ameliorates lipopolysaccharide‑induced HK‑2 cell apoptosis and inflammation by regulating endoplasmic reticulum stress". Experimental and Therapeutic Medicine 24, no. 2 (2022): 513. https://doi.org/10.3892/etm.2022.11440
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang Y, Yu C and Feng Y: Pinocembrin ameliorates lipopolysaccharide‑induced HK‑2 cell apoptosis and inflammation by regulating endoplasmic reticulum stress. Exp Ther Med 24: 513, 2022.
APA
Zhang, Y., Yu, C., & Feng, Y. (2022). Pinocembrin ameliorates lipopolysaccharide‑induced HK‑2 cell apoptosis and inflammation by regulating endoplasmic reticulum stress. Experimental and Therapeutic Medicine, 24, 513. https://doi.org/10.3892/etm.2022.11440
MLA
Zhang, Y., Yu, C., Feng, Y."Pinocembrin ameliorates lipopolysaccharide‑induced HK‑2 cell apoptosis and inflammation by regulating endoplasmic reticulum stress". Experimental and Therapeutic Medicine 24.2 (2022): 513.
Chicago
Zhang, Y., Yu, C., Feng, Y."Pinocembrin ameliorates lipopolysaccharide‑induced HK‑2 cell apoptosis and inflammation by regulating endoplasmic reticulum stress". Experimental and Therapeutic Medicine 24, no. 2 (2022): 513. https://doi.org/10.3892/etm.2022.11440
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