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

• Published in: Cellular physiology and biochemistry Vol. 42; no. 2; pp. 824 - 837
• Main Authors: Dong, Zhiwei, Zhou, Jian, Zhang, Ying, Chen, Yajie, Yang, Zichen, Huang, Guangtao, Chen, Yu, Yuan, Zhiqiang, Peng, Yizhi, Cao, Tongtong
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2017; Cell Physiol Biochem Press GmbH & Co KG
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Astragaloside-IV; Autophagy; Autophagy - drug effects; Autophagy - genetics; Cancer; Disease; eIF-2 Kinase - genetics; Endoplasmic reticulum; Endoplasmic Reticulum - drug effects; Endoplasmic Reticulum - genetics; Endoplasmic reticulum stress; Endoplasmic Reticulum Stress - drug effects; Endoplasmic Reticulum Stress - genetics; Eukaryotic Initiation Factor-2 - genetics; Fever; Homeostasis; Hot Temperature - adverse effects; Hyperthermia; Inflammation; Inflammation - drug therapy; Inflammation - genetics; Inflammation - pathology; Kinases; Original Paper; Oxidative stress; Pathogenesis; Rats; Rats, Wistar; Reactive Oxygen Species - metabolism; Rodents; ROS; Saponins - administration & dosage; Sepsis; Signal Transduction - drug effects; Spinal cord; Triterpenes - administration & dosage; China; Astragaloside-IV; Inflammation; Autophagy; ROS; Endoplasmic reticulum stress
• ISSN: 1015-8987; 1421-9778
• DOI: 10.1159/000478626

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.