Protective effects of chelerythrine against lipopolysaccharide-induced endotoxic shock in mice.

Chelerythrine (CHE), a quaternary benzo[c]phenanthridine alkaloid, exhibits a wide spectrum of pharmacological effects. Although CHE has been used to treat various diseases, the protective effects of CHE on lipopolysaccharide (LPS)-induced endotoxic shock have not been explored. The aims of the study were to investigate the protective effects of CHE on LPS-induced endotoxic shock in mice and clarify the mechanism of the effects. We found that pretreatment with CHE (1, 5, and 10 mg/kg, po) at 1 and 12 h before injected intraperitoneally with 1 mg/kg LPS markedly decreased the production of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and myeloperoxidase (MPO) and attenuated the lung histopathological changes. Meanwhile, the effects were dependent on the inhibition of the expression of p65 nuclear factor κB (NF-κB). The protective effects of CHE on LPS-induced endotoxic shock can be attributed to attenuating inflammatory cytokines and inhibition of the expression of NF-κB.