On-line Access: 2021-11-16
Revision Accepted: 2021-02-21
Citations: Bibtex RefMan EndNote GB/T7714
Xingchi KAN, Yingsheng CHEN, Bingxu HUANG, Shoupeng FU, Wenjin GUO, Xin RAN, Yu CAO, Dianwen XU, Ji CHENG, Zhanqing YANG, Yanling XU.
author="Xingchi KAN, Yingsheng CHEN, Bingxu HUANG, Shoupeng FU, Wenjin GUO, Xin RAN, Yu CAO, Dianwen XU, Ji CHENG, Zhanqing YANG, Yanling XU",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",
%0 Journal Article
%A Xingchi KAN
%A Yingsheng CHEN
%A Bingxu HUANG
%A Shoupeng FU
%A Wenjin GUO
%A Xin RAN
%A Yu CAO
%A Dianwen XU
%A Ji CHENG
%A Zhanqing YANG
%A Yanling XU
%J Journal of Zhejiang University SCIENCE B
%I Zhejiang University Press & Springer
TY - JOUR
A1 - Xingchi KAN
A1 - Yingsheng CHEN
A1 - Bingxu HUANG
A1 - Shoupeng FU
A1 - Wenjin GUO
A1 - Xin RAN
A1 - Yu CAO
A1 - Dianwen XU
A1 - Ji CHENG
A1 - Zhanqing YANG
A1 - Yanling XU
J0 - Journal of Zhejiang University Science B
VL - 22
IS - 11
SP - 929
EP - 940
Y1 - 2021
PB - Zhejiang University Press & Springer
DOI - 10.1631/jzus.B2000583
Abstract: Inflammation plays an important role in the development of acute lung injury (ALI). Severe pulmonary inflammation can cause acute respiratory distress syndrome (ARDS) or even death. Expression of proinflammatory interleukin-1β(IL-1β) and inducible nitric oxide synthase (iNOS) in the process of pulmonary inflammation will further exacerbate the severity of ALI. The purpose of this study was to explore the effect of palrnatine (Pa) on lipopolysaccharide (LPS)-induced mouse ALI and its underlying mechanism. Pa, a natural product, has a wide range of pharmacological activities with the potential to protect against lung injury. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) assays were performed to detect the expression and translation of inflammatory genes and proteins in vitro and in vivo. Immunoprecipitation was used to detect the degree of P65 translocation into the nucleus. We also used molecular modeling to further clarify the mechanism of action. The results showed that Pa pretreatment could significantly inhibit the expression and secretion of the inflammatory cytokine IL-1β, and significantly reduce the protein level of the proinflammatory protease iNOS, in both in vivo and in vitro models induced by LPS. Further mechanism studies showed that Pa could significantly inhibit the activation of the protein kinase B (Akt)/nuclear factor-κB (NF-κb) signaling pathway in the LPS-induced ALI mode and in LPS-induced RAW264.7 cells. Through molecular dynamics simulation, we observed that Pa was bound to the catalytic pocket of Akt and effectively inhibited the biological activity of Akt. These results indicated that Pa significantly relieves LPS-induced ALI by activating the Akt/NF-κB signaling pathway.
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