Journal of Inflammation Research (Oct 2021)

Capsaicin Protects Against Lipopolysaccharide-Induced Acute Lung Injury Through the HMGB1/NF-κB and PI3K/AKT/mTOR Pathways

  • Chen H,
  • Li N,
  • Zhan X,
  • Zheng T,
  • Huang X,
  • Chen Q,
  • Song Z,
  • Yang F,
  • Nie H,
  • Zhang Y,
  • Zheng B,
  • Gong Q

Journal volume & issue
Vol. Volume 14
pp. 5291 – 5304


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Hui Chen,1,* Na Li,1,2,* Xiang Zhan,1,* Ting Zheng,1 Xinzhou Huang,1 Qianglin Chen,1 Zihao Song,1 Fei Yang,1,3 Hao Nie,1,3 Yanxiang Zhang,3 Bing Zheng,1,3 Quan Gong1,3 1Department of Immunology, School of Medicine, Yangtze University, Jingzhou, People’s Republic of China; 2Department of Oncology, First Affiliated Hospital of Yangtze University, Jingzhou, Hubei, People’s Republic of China; 3Clinical Molecular Immunology Center, School of Medicine, Yangtze University, Jingzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bing Zheng; Quan GongDepartment of Immunology, School of Medicine, Yangtze University, Jingzhou, People’s Republic of ChinaEmail [email protected]; [email protected]: Capsaicin (8-methyl-N-geranyl-6-nonamide; CAP) is an alkaloid isolated from chili peppers, which has complex pharmacological properties, including beneficial effects against various diseases. The aim of this study was to investigate the role of CAP in lipopolysaccharide (LPS)-induced acute lung injury (ALI), and the possible underlying mechanisms.Materials and Methods: ALI was induced by intranasal administration of LPS (0.5 mg/kg), and CAP (1 mg/kg) injected intraperitoneally 3 days before exposure to LPS. Then, the histopathological changes were evaluated by hematoxylin and eosin staining. Enzyme-linked immunosorbent assay and qPCR were used to detect pro-inflammatory cytokines in serum and lung tissue. The expressions of HMGB1/NF-κB, PI3K/AKT/mTOR signaling pathways and apoptosis-associated molecules were determined by Western blot and/or qPCR. In addition, the lung cell apoptosis was analyzed by TUNEL staining, and the expression and location of cleaved caspase-3 were detected by immunofluorescence analysis.Results: CAP pretreatment significantly protected mice from LPS-induced ALI, with reduced lung wet/dry weight ratio, lung histological damage, myeloperoxidase (MPO) activity, malondialdehyde (MDA) content and pro-inflammatory cytokine levels, and significant increased superoxide dismutase (SOD) activity. In addition, CAP pretreatment significantly inhibited the high-mobility group protein B1 (HMGB1) expression, nuclear factor-kappa B (NF-κB) activation, and the PI3K/AKT/mTOR signaling pathway. Furthermore, mice pre-treated with CAP exhibited reduced apoptosis of lung tissues, with associated down-regulation of caspase-3, cleaved caspase-3, and BAX expression, and up-regulation of BCL-2.Conclusion: Our data demonstrate that CAP can protect against LPS-induced ALI by inhibiting oxidative stress, inflammatory responses and apoptosis through down-regulation of the HMGB1/NF-κB and PI3K/AKT/mTOR pathways.Keywords: capsaicin, acute lung injury, HMGB1/NF-κB, PI3K/AKT/mTOR, apoptosis, inflammation