αBκ
信号转导
NF-κB
免疫印迹
药效团
化学
肿瘤坏死因子α
分子生物学
NFKB1型
脂多糖
磷酸化
药理学
生物
转录因子
免疫学
生物化学
基因
作者
Liping Dai,Hong Wu,Ming Gong,Xinzhou Wang,Lili Wang,Zhimin Wang,Liping Dai,Xu Erping
摘要
Abstract Chronic pharyngitis (CP) is an inflammatory disease of the pharyngeal mucosa and its lymphatic tissues that is difficult to treat clinically. However, research on the exact therapeutic agents and molecular mechanisms of CP is still unclear. In this study, we investigated Rabdosichuanin C (RC) to attenuate lipopolysaccharide (LPS)‐induced inflammatory damage in RAW264.7 cells by a combination of targeted virtual screening and in vitro activity assay and further clarified its molecular mechanism of action centering on the IκB/nuclear factor kappa B (NF‐κB) pathway. Molecular docking and pharmacophore simulation methods were used to screen compounds with IκB inhibitory effects. Expression of genes and proteins related to the IκB/NF‐κB signaling pathway by RC in LPS‐induced inflammatory injury model of RAW264.7 cells was detected by PCR, enzyme‐linked immunosorbent assay, and Western blot. The docking of RC with IκB protein showed good binding energy, and pharmacophore simulations further confirmed the active effect of RC in inhibiting IκB protein. RC intervention in LPS‐induced RAW264.7 cells significantly reduced the expression levels of inflammatory factors tumor necrosis factor‐α, interleukins‐6, iNOS, and CD‐86 at the messenger RNA and protein levels, downregulated IκB, p65 protein phosphorylation levels, and significantly inhibited IκB/NF‐κB signaling pathway activation. Virtual screening provided us with an effective method to rapidly identify compounds RC that target inhibit the action of IκB, and the activity results showed that RC inhibits NF‐κB signaling pathway activation. It is suggested that RC may play a role in the treatment of CP by inhibiting the IκB/NF‐κB signaling pathway.
科研通智能强力驱动
Strongly Powered by AbleSci AI