1. Astragaloside-IV Alleviates Heat-Induced Inflammation by Inhibiting Endoplasmic Reticulum Stress and Autophagy.
- Author
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Dong, Zhiwei, Zhou, Jian, Zhang, Ying, Chen, Yajie, Yang, Zichen, Huang, Guangtao, Chen, Yu, Yuan, Zhiqiang, Peng, Yizhi, and Cao, Tongtong
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INFLAMMATION treatment , *ASTRAGALUS membranaceus , *PHYSIOLOGICAL effects of heat , *ENDOPLASMIC reticulum , *AUTOPHAGY , *INFLAMMATION , *POLYMERASE chain reaction , *PHYSIOLOGY - Abstract
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 ofinduces 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. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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