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Chelerythrine Attenuates the Inflammation of Lipopolysaccharide-Induced Acute Lung Inflammation Through NF-?B Signaling Pathway Mediated by Nrf2.

ABSTRACT: Chelerythrine (CH), is a kind of benzo[c] phenanthridine alkaloid isolated from plants such as Chelidonium, with pharmacological activities as antitumor, antibiosis and anti-inflammation. However, few studies have demonstrated whether CH could protect against lipopolysaccharide (LPS)-induced acute lung injury (ALI), and the underlying mechanism is also uncertain. The purpose of the present study was to investigate the anti-inflammatory effects of CH on LPS-induced ALI in mice and in RAW264.7 cells. In this study, we demonstrated that treatment with CH significantly ameliorated LPS-induced pathological changes in the lung. CH also attenuated LPS-induced W/D ratio, inflammatory cell infiltration. Meanwhile, LPS-induced Tumor necrosis factor-alpha (TNF-?), interleukin 6 (IL-6), and interleukin 1? (IL-1?) production and oxidative stress were markedly suppressed by CH. Furthermore, western blot showed that CH suppressed LPS-stimulated inflammation of RAW264.7 cells through activation of nuclear factor kappa-B (NF-?B) pathway. Knocking down of nuclear factor erythroid 2-related factor 2 (Nrf2) led to the reduction of nuclear translocation of the NF-?B p65, which triggered inflammation. These experimental results provided evidence that CH could be a potential therapeutic candidate for the intervention of ALI caused by LPS.


PROVIDER: S-EPMC6169195 | BioStudies | 2018-01-01

REPOSITORIES: biostudies

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