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

免疫印迹 脂多糖 药理学 化学 NF-κB 体内 肿瘤坏死因子α αBκ 炎症 传统医学 生物化学 信号转导 医学 免疫学 生物 内科学 生物技术 基因
作者
Xin Jin,Xu Gao,Meng Lan,Chunnan Li,Jiaming Sun,Hui Zhang
出处
期刊:Chemical Biology & Drug Design [Wiley]
卷期号:99 (5): 717-726 被引量:9
标识
DOI:10.1111/cbdd.14013
摘要

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, 25 μg/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 (10 mg/kg) was given intraperitoneally to establish ALI model, and compound G (2.5 or 10 mg/kg) was injected into mice as the experimental group. The results showed that after the compound G (10 mg/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 (10 mg/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.
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