Astragaloside-IV Alleviates Heat-Induced Inflammation by Inhibiting Endoplasmic Reticulum Stress and Autophagy

Cell Physiol Biochem. 2017;42(2):824-837. doi: 10.1159/000478626. Epub 2017 Jun 23.


Background: Thermal injury is the main cause of pulmonary disease in stroke after burn and can be life threatening. Heat-induced inflammation is an important factor that triggers a series of induces pathological changes. However, this mechanism underlying heat-induced inflammation in thermal inhalation injury remains unclear. Studies have revealed that astragaloside-IV (AS-IV), a natural compound extracted from Astragalus membranaceus, has protective effects in inflammatory diseases. Here, we investigated whether the protective effects of AS-IV occur because of the suppression of heat-induced endoplasmic reticulum (ER) stress and excessive autophagy Methods: AS-IV was administered to Wistar rats after thermal inhalation injury and 16HBE140-cells were treated with AS-IV. TNF-α, IL-6, and IL-8 levels were determined by ELISA and real-time PCR. ER stress and autophagy were determined by western blot. Autophagic flux was measured by recording the fluorescence emission of the fusion protein mRFP-GFP-LC3 by dynamic live-cell imaging.

Results: AS-IV had protective effects against heat-induced reactive oxygen species production and attenuated ER stress. AS IV alleviated heat-induced excessive autophagy in vitro and in vivo. Excessive autophagy was attenuated by the PERK inhibitor GSK2656157 and eIF2α siRNA, suggesting that heat stress-induced autophagy can activate the PERK-eIF2α pathway. Beclin 1 and Atg5 siRNAs inhibited the upregulation of the inflammatory cytokines TNF-α, IL-6, and IL-8 after heat exposure.

Conclusions: Thus, AS-IV may attenuate inflammatory responses by disrupting the crosstalk between autophagy and the PERK-eIF2α pathway and may be an ideal agent for treating inflammatory pulmonary diseases.

Keywords: Astragaloside-IV; Autophagy; Endoplasmic reticulum stress; Inflammation; ROS.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Autophagy / drug effects
  • Autophagy / genetics
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / genetics
  • Endoplasmic Reticulum Stress / drug effects*
  • Endoplasmic Reticulum Stress / genetics
  • Eukaryotic Initiation Factor-2 / genetics*
  • Hot Temperature / adverse effects
  • Inflammation / drug therapy*
  • Inflammation / genetics
  • Inflammation / pathology
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Saponins / administration & dosage*
  • Signal Transduction / drug effects
  • Triterpenes / administration & dosage*
  • eIF-2 Kinase / genetics*


  • Eukaryotic Initiation Factor-2
  • Reactive Oxygen Species
  • Saponins
  • Triterpenes
  • astragaloside A
  • PERK kinase
  • eIF-2 Kinase