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On-line Access: 2021-11-16

Received: 2020-09-23

Revision Accepted: 2021-02-21

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Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Xingchi KAN

https://orcid.org/0000-0002-3541-4997

Yanling XU

https://orcid.org/0000-0002-0544-6517

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Journal of Zhejiang University SCIENCE B 2021 Vol.22 No.11 P.929-940

http://doi.org/10.1631/jzus.B2000583


Effect of Palrnatine on lipopolysaccharide-induced acute lung injury by inhibiting activation of the Akt/NF-κB pathway


Author(s):  Xingchi KAN, Yingsheng CHEN, Bingxu HUANG, Shoupeng FU, Wenjin GUO, Xin RAN, Yu CAO, Dianwen XU, Ji CHENG, Zhanqing YANG, Yanling XU

Affiliation(s):  Department of Theoretic Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun 130012, China; more

Corresponding email(s):   xuyanling0719@sina.com

Key Words:  Acute lung injury, Palrnatine, Lipopolysaccharide (LPS), Protein kinase B/nuclear factor-κ, B (Akt/NF-κ, B)


Xingchi KAN, Yingsheng CHEN, Bingxu HUANG, Shoupeng FU, Wenjin GUO, Xin RAN, Yu CAO, Dianwen XU, Ji CHENG, Zhanqing YANG, Yanling XU. Effect of Palrnatine on lipopolysaccharide-induced acute lung injury by inhibiting activation of the Akt/NF-κB pathway[J]. Journal of Zhejiang University Science B, 2021, 22(11): 929-940.

@article{title="Effect of Palrnatine on lipopolysaccharide-induced acute lung injury by inhibiting activation of the Akt/NF-κB pathway",
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",
volume="22",
number="11",
pages="929-940",
year="2021",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2000583"
}

%0 Journal Article
%T Effect of Palrnatine on lipopolysaccharide-induced acute lung injury by inhibiting activation of the Akt/NF-κB pathway
%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
%V 22
%N 11
%P 929-940
%@ 1673-1581
%D 2021
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2000583

TY - JOUR
T1 - Effect of Palrnatine on lipopolysaccharide-induced acute lung injury by inhibiting activation of the Akt/NF-κB pathway
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
%@ 1673-1581
Y1 - 2021
PB - Zhejiang University Press & Springer
ER -
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.

掌叶防己碱通过抑制Akt/NF-κB信号通路的激活来缓解脂多糖诱导的急性肺损伤

目的:探讨掌叶防己碱对脂多糖(LPS)诱导的小鼠急性肺损伤的作用及其潜在机制。
创新点:(1)利用分子生物学技术预测出掌叶防己碱与蛋白激酶B(Akt)的氨基酸残基苏氨酸(THR-51)之间存在氢键作用;(2)确证掌叶防己碱在LPS诱导的急性肺损伤中具有抗炎作用,有助于全面认识掌叶防己碱的生物学功能;(3)为临床缓解急性肺损伤提供潜在的有效药物,作为一种天然抗炎症药物在急性肺损伤临床的应用提供理论依据。
方法:采用蛋白质印迹法(western blot)和实时荧光定量聚合酶链式反应(qRT-PCR)检测炎症基因和炎症蛋白在体内外的转录和翻译;使用免疫荧光法检测促炎转录因子核因子κB(NF-κB)P65转位进入细胞核程度;利用分子对接的方法模拟预测掌叶防己碱与Akt蛋白是否存在氢键作用。
结论:研究结果表明,掌叶防己碱预处理能显著抑制LPS诱导的体内外炎症细胞因子白细胞介素IL-1β的表达和分泌,显著降低促炎性蛋白酶诱导型一氧化氮合酶(iNOS)的蛋白水平。机制研究结果进一步表明,掌叶防己碱能显著抑制LPS诱导的急性肺损伤模型和LPS诱导的小鼠单核巨噬细胞(RAW264.7)细胞的Akt/NF-κB信号通路的激活。通过分子动力学模拟,我们观察到掌叶防己碱与Akt之间存在的氢键作用,有效地抑制了Akt的生物活性。综上所述,掌叶防己碱通过抑制Akt/NF-κB信号通路的激活有效地缓解了LPS诱导的急性肺损伤。

关键词:急性肺损伤;掌叶防己碱;脂多糖(LPS);蛋白激酶B/核因子κB(Akt/NF-κB)

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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