Rutaecarpine ameliorates lipopolysaccharide‑induced BEAS‑2B cell injury through inhibition of endoplasmic reticulum stress via activation of the AMPK/SIRT1 signaling pathway

Zhang,Hao; Zhu,Kun; Zhang,Xuefeng; Ding,Yihui; Zhu,Bing; Meng,Wen; Zhang,Fan

doi:10.3892/etm.2022.11300

Rutaecarpine ameliorates lipopolysaccharide‑induced BEAS‑2B cell injury through inhibition of endoplasmic reticulum stress via activation of the AMPK/SIRT1 signaling pathway

Authors:
- Hao Zhang
- Kun Zhu
- Xuefeng Zhang
- Yihui Ding
- Bing Zhu
- Wen Meng
- Fan Zhang
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Affiliations: Emergency Department, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P.R. China, Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Qiqihar Medical College, Qiqihar, Heilongjiang 161000, P.R. China, Department of Cardiothoracic Surgery, The Affiliated Heilongjiang Provincial Hospital of Harbin Institute of Technology, Harbin, Heilongjiang 150036, P.R. China, Department of Cardiothoracic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P.R. China
Published online on: April 6, 2022 https://doi.org/10.3892/etm.2022.11300
Article Number: 373
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Rutaecarpine (RUT) is an alkaloid isolated from Tetradium ruticarpum, which has been reported to protect against several inflammatory diseases. However, to the best of our knowledge, the role of RUT in acute lung injury (ALI) and the specific molecular mechanism remain unknown. In the present study, an in vitro model of ALI was established in BEAS‑2B cells by lipopolysaccharide (LPS) administration. Cell viability following RUT treatment with or without LPS stimulation was evaluated using a Cell Counting Kit‑8 assay. The inflammatory response and oxidative stress were detected using ELISA kits and commercially available kits, respectively. TUNEL assay and western blotting were performed to assess cell apoptosis. The expression levels of endoplasmic reticulum (ER) stress‑related proteins and AMP‑activated protein kinase (AMPK)/sirtuin 1 (SIRT1) signaling pathway‑related proteins were measured by western blotting. The results revealed that RUT markedly improved cell viability after LPS treatment in a dose‑dependent manner. In addition, RUT inhibited the LPS‑induced inflammatory response and oxidative stress in BEAS‑2B cells, and suppressed the LPS‑induced apoptosis of BEAS‑2B cells. Mechanistically, RUT alleviated ER stress by inhibiting the production of CHOP, glucose‑regulated protein‑78, caspase‑12 and activating transcription factor 6. Additionally, western blotting demonstrated that RUT activated the phosphorylation of AMPK and SIRT1, which indicated the involvement of the AMPK/SIRT1 signaling pathway in the protective effect of RUT against LPS‑induced lung injury. In conclusion, these results demonstrated that RUT mitigated LPS‑induced lung cell injury by inhibiting ER stress via the activation of the AMPK/SIRT1 signaling pathway.

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