Clemaichinenoside protects renal tubular epithelial cells from hypoxia/reoxygenation injury in vitro through activating the Nrf2/HO-1 signalling pathway

Clin Exp Pharmacol Physiol. 2020 Mar;47(3):495-502. doi: 10.1111/1440-1681.13219. Epub 2019 Dec 22.

Abstract

Renal ischaemia/reperfusion (I/R) is a major cause of acute renal failure with increased morbidity, mortality, and prolonged hospitalizations. Clematichinenoside (AR), a triterpenoid saponin isolated from the roots of Clematis chinensis, was reported to possess a protective effect against I/R injury. However, the effect of AR on renal I/R injury has not been evaluated. This study aims to examine the effect of AR on an in vitro I/R model in human proximal tubular epithelial cells HK-2. HK-2 cells were subjected to hypoxia/reoxygenation (H/R) stimulation to mimic I/R in vitro. The results showed that AR improved cell viability of H/R-stimulated HK-2 cells. AR pretreatment resulted in decreased production of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as increased in superoxide dismutase (SOD) activity in H/R-stimulated HK-2 cells. In addition, AR also presented an anti-inflammatory activity, as evidenced by decreased secretion of pro-inflammatory cytokines including IL-6, IL-1β, and TNF-α. Moreover, apoptotic rate was markedly decreased in HK-2 cells pretreated with AR. The bax expression was decreased, while bcl-2 expression was increased by AR pretreatment. Furthermore, AR enhanced the H/R-stimulated activation of the Nrf2/HO-1 signalling pathway in HK-2 cells. In conclusion, these findings indicated that AR protected HK-2 cells from H/R-induced cell injury via regulating the Nrf2/HO-1 signalling pathway.

Keywords: Nrf2/HO-1 signalling pathway; clematichinenoside (AR); inflammation; oxidative stress; renal ischaemia/reperfusion (I/R).

MeSH terms

  • Cell Hypoxia / drug effects
  • Cell Hypoxia / physiology
  • Cell Line
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Heme Oxygenase-1 / metabolism*
  • Humans
  • Kidney Tubules, Proximal / cytology
  • Kidney Tubules, Proximal / drug effects
  • Kidney Tubules, Proximal / metabolism*
  • NF-E2-Related Factor 2 / metabolism*
  • Saponins / pharmacology*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*

Substances

  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Saponins
  • clematichinenoside
  • HMOX1 protein, human
  • Heme Oxygenase-1