Journal
JOURNAL OF INFLAMMATION RESEARCH
Volume 14, Issue -, Pages 5291-5304Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/JIR.S309457
Keywords
capsaicin; acute lung injury; HMGB1/NF-kappa B; PI3K/AKT/mTOR; apoptosis; inflammation
Categories
Funding
- Joint Foundation of the Health Commission of Hubei Province [WJ2018H173]
- Central Funds Guiding the Local Science and Technology Development of Hubei Province [2019ZYYD066]
- National Natural Science Foundation of China [81271872]
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Our study demonstrates that CAP can protect against LPS-induced ALI by inhibiting oxidative stress, inflammatory responses and apoptosis through down-regulation of the HMGB1/NF-kappa B and PI3K/AKT/mTOR pathways. The results showed that CAP pretreatment significantly protected mice from LPS-induced ALI, with reduced lung histological damage, pro-inflammatory cytokine levels, and increased antioxidant activity.
Purpose: 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-kappa B, 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-kappa B) 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-kappa B and PI3K/AKT/mTOR pathways.
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