Salidroside protects renal tubular epithelial cells from hypoxia/reoxygenation injury in vitro

J Pharmacol Sci. 2018 Jun;137(2):170-176. doi: 10.1016/j.jphs.2018.05.011. Epub 2018 Jun 18.

Abstract

Oxidative stress, inflammation and cell apoptosis are important mechanisms of renal ischemia/reperfusion (I/R) injury. Salidroside, a natural phenylpropanoid glycoside, possesses anti-inflammatory, anti-oxidative, and anti-apoptotic effects. However, the effect of salidroside on renal I/R injury has not been fully elucidated. The present study aimed to investigate the effect of salidroside on renal I/R injury in vitro. Our results showed that salidroside improved the viability of human renal tubular epithelial cells (HK-2) in response to hypoxia/reoxygenation (H/R). Salidroside caused apparent decrease in the levels of reactive oxygen species (ROS) and malondiaidehyde (MDA), and significant increase in superoxide dismutase (SOD) activity in HK-2 cells. Pretreatment with salidroside markedly inhibited the production levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 in a dose-dependent manner. Salidroside treatment exhibited significant increase in Bcl-2 expressions, and decrease in Bax expressions and caspase-3 activity when compared with the H/R group. Salidroside decreased the levels of toll-like receptor 4 (TLR4) and p-p65 in HK-2 cells. Overexpression of TLR4 significantly attenuated the effects of salidroside on cell viability, oxidative stress, cytokine production and cell apoptosis in HK-2 cells. These findings indicated that salidroside protected HK-2 cells from H/R stimulation, which was mediated by the TLR4/NF-κB pathway.

Keywords: Acute kidney injury (AKI); Hypoxia/reoxygenation (H/R); Inflammation; Ischemia/reperfusion (I/R); Oxidative stress; Salidroside.

MeSH terms

  • Anti-Inflammatory Agents*
  • Antioxidants*
  • Caspase 3 / metabolism
  • Cell Survival / drug effects
  • Cells, Cultured
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Glucosides / pharmacology*
  • Glucosides / therapeutic use*
  • Humans
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Ischemia / prevention & control*
  • Kidney / blood supply*
  • Kidney Tubules / cytology
  • Malondialdehyde / metabolism
  • NF-kappa B / metabolism
  • Phenols / pharmacology*
  • Phenols / therapeutic use*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / metabolism
  • Reperfusion Injury / prevention & control*
  • Signal Transduction / drug effects
  • Superoxide Dismutase / metabolism
  • Toll-Like Receptor 4 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • bcl-2-Associated X Protein / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Glucosides
  • Interleukin-1beta
  • Interleukin-6
  • NF-kappa B
  • Phenols
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • bcl-2-Associated X Protein
  • Malondialdehyde
  • Superoxide Dismutase
  • Caspase 3
  • rhodioloside