Study the mechanism of peimisine derivatives on NF-κB inflammation pathway on mice with acute lung injury induced by lipopolysaccharide.

Abstract

Peimisine is one of the alkaloids in Fritillariae ussuriensis Bulbus, which has anti-acute lung injury effect. In order to obtain compounds with superior bio-activity, 14 new derivatives were obtained from peimisine, and the better activity compounds were screened by MTT method. It was found that boc-leucine mono peimisine ester monoamide (compound G, 25μg/ml) had increased cell survival rate and reduced the TNF-α, IL-1β, IL-6, and iNOS levels in RAW 264.7 by lipopolysaccharide (LPS)-stimulated. In vivo, LPS (10mg/kg) was given intraperitoneally to establish ALI model, and compound G (2.5 or 10mg/kg) was injected into mice as the experimental group. The results showed that after the compound G (10mg/kg) treatment, the Wet / Dry ratio of the lung was reduced, and the expression of TNF-α, IL-1β, IL-6 and iNOS was inhibited. Meanwhile, compound G (10mg/kg) could increase the content of IκB protein and reduce the content of p65 protein in lung tissue by Western blot analysis, which may play an anti-acute lung injury role by inhibiting the activity of NF-κB signaling pathway. In conclusion, compound G could attenuate LPS-induced ALI in mice and it may become a new approach to treat ALI.