Full Text:   <1814>

Summary:  <867>

CLC number: 

On-line Access: 2021-11-16

Received: 2020-09-23

Revision Accepted: 2021-02-21

Crosschecked: 0000-00-00

Cited: 0

Clicked: 2929

Citations:  Bibtex RefMan EndNote GB/T7714


Xingchi KAN


Yanling XU


-   Go to

Article info.
Open peer comments

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


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",
publisher="Zhejiang University Press & Springer",

%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 Dianwen XU
%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

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 - 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

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.


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。


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


[1]BellinganGJ, 2002. The pulmonary physician in critical care · 6: the pathogenesis of ALI/ARDS. Thorax, 57(6):540-546.

[2]BrielM, MeadeM, MercatA, et al., 2010. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. JAMA, 303(9):865-873.

[3]BuccellettiF, MazzoneM, PortaleG, et al., 2003. Humoral and cellular inflammatory mediators in acute lung injury: friends or enemies? Minerva Med, 94(3):157-165.

[4]ChauhanPS, SinghDK, DashD, et al., 2018. Intranasal curcumin regulates chronic asthma in mice by modulating NF-‍κB activation and MAPK signaling. Phytomedicine, 51:29-38.

[5]DengJW, YangQ, CaiXP, et al., 2020. Early use of dexamethasone increases Nr4a1 in Kupffer cells ameliorating acute liver failure in mice in a glucocorticoid receptor-dependent manner. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 21(9):727-739.

[6]FuSP, WangJF, XueWJ, et al., 2015. Anti-inflammatory effects of BHBA in both in vivo and in vitro Parkinson's disease models are mediated by GPR109A-dependent mechanisms. J Neuroinflammation, 12:9.

[7]GandhirajanRK, MengS, ChandramoorthyHC, et al., 2013. Blockade of NOX2 and STIM1 signaling limits lipopolysaccharide-induced vascular inflammation. J Clin Invest, 123(2):887-902.

[8]GaoY, XiaoXS, ZhangCL, et al., 2017. Melatonin synergizes the chemotherapeutic effect of 5-fluorouracil in colon cancer by suppressing PI3K/AKT and NF-‍κB/iNOS signaling pathways. J Pineal Res, 62(2):e12380.

[9]GoodmanRB, PuginJ, LeeJS, et al., 2003. Cytokine-mediated inflammation in acute lung injury. Cytokine Growth Factor Rev, 14(6):523-535.

[10]GuoWJ, LiuBR, HuGQ, et al., 2019. Vanillin protects the blood-milk barrier and inhibits the inflammatory response in LPS-induced mastitis in mice. Toxicol Appl Pharmacol, 365:9-18.

[11]HeM, IchinoseT, SongY, et al., 2016. Desert dust induces TLR signaling to trigger Th2-dominant lung allergic inflammation via a MyD88-dependent signaling pathway. Toxicol Appl Pharmacol, 296:61-72.

[12]HouW, HuSY, SuZZ, et al., 2018. Myricetin attenuates LPS-induced inflammation in RAW 264.7 macrophages and mouse models. Future Med Chem, 10(19):2253-2264.

[13]JeonJ, LeeY, YuH, et al., 2020. HSP70-homolog DnaK of Pseudomonas aeruginosa increases the production of IL-27 through expression of EBI3 via TLR4-dependent NF-‍κB and TLR4-independent Akt signaling. Int J Mol Sci, 21(23):9194.

[14]JinMY, FengHH, WangY, et al., 2020. Gentiopicroside ameliorates oxidative stress and lipid accumulation through nuclear factor erythroid 2-related factor 2 activation. Oxid Med Cell Longev, 2020:2940746.

[15]KanXC, LiuBR, GuoWJ, et al., 2019. Myricetin relieves LPS-induced mastitis by inhibiting inflammatory response and repairing the blood-milk barrier. J Cell Physiol, 234(9):16252-16262.

[16]LiuS, ZhangJ, ZhouYL, et al., 2019. Pterostilbene restores carbapenem susceptibility in New Delhi metallo-‍β‍-lactamase-producing isolates by inhibiting the activity of New Delhi metallo-‍β‍-lactamases. Br J Pharmacol, 176(23):4548-4557.

[17]LvHM, LiuQM, WenZM, et al., 2017. Xanthohumol ameliorates lipopolysaccharide (LPS)‍-induced acute lung injury via induction of AMPK/GSK3β-Nrf2 signal axis. Redox Biol, 12:311-324.

[18]MaiCT, WuMM, WangCL, et al., 2019. Palmatine attenuated dextran sulfate sodium (DSS)-induced colitis via promoting mitophagy-mediated NLRP3 inflammasome inactivation. Mol Immunol, 105:76-85.

[19]MeiSH, McCarterSD, DengYP, et al., 2007. Prevention of LPS-induced acute lung injury in mice by mesenchymal stem cells overexpressing angiopoietin 1. PLoS Med, 4(9):e269.

[20]MetzC, SibbaldWJ, 1991. Anti-inflammatory therapy for acute lung injury: a review of animal and clinical studies. Chest J, 100(4):1110-1119.

[21]NennigSE, SchankJR, 2017. The role of NFkB in drug addiction: beyond inflammation. Alcohol Alcohol, 52(2):172-179.

[22]NingK, GuanZB, LuHT, et al., 2020. Lung macrophages are involved in lung injury secondary to repetitive diving. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 21(8):646-656.

[23]PatelA, KhandeH, PeriasamyH, et al., 2020. Immunomodulatory effect of doxycycline ameliorates systemic and pulmonary inflammation in a murine polymicrobial sepsis model. Inflammation, 43(3):1035-1043.

[24]PedrazzaL, CunhaAA, LuftC, et al., 2017. Mesenchymal stem cells improves survival in LPS-induced acute lung injury acting through inhibition of NETs formation. J Cell Physiol, 232(12):3552-3564.

[25]SangarajuR, NalbanN, AlavalaS, et al., 2019. Protective effect of galangin against dextran sulfate sodium (DSS)-induced ulcerative colitis in Balb/c mice. Inflamm Res, 68(8):691-704.

[26]SlomianyBL, SlomianyA, 2017. Role of LPS-elicited signaling in triggering gastric mucosal inflammatory responses to H. pylori: modulatory effect of ghrelin. Inflammopharmacology, 25(4):415-429.

[27]SongCY, XuYG, LuYQ, 2020. Use of Tripterygium wilfordii Hook F for immune-mediated inflammatory diseases: progress and future prospects. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 21(4):280-290.

[28]SongYD, WuYX, LiXZ, et al., 2018. Protostemonine attenuates alternatively activated macrophage and DRA-induced asthmatic inflammation. Biochem Pharmacol, 155:198-206.

[29]SoniS, WilsonMR, O'DeaKP, et al., 2016. Alveolar macrophage-derived microvesicles mediate acute lung injury. Thorax, 71(11):1020-1029.

[30]TangJ, XuLQ, ZengYW, et al., 2021. Effect of gut microbiota on LPS-induced acute lung injury by regulating the TLR4/NF-‍κB signaling pathway. Int Immunopharmacol, 91:107272.

[31]The National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, 2006. Pulmonary-artery versus central venous catheter to guide treatment of acute lung injury. N Engl J Med, 354(21):2213-2224.

[32]TsushimaK, KingLS, AggarwalNR, et al., 2009. Acute lung injury review. Intern Med, 48(9):621-630.

[33]XiangYN, GuoZM, ZhuPF, et al., 2019. Traditional Chinese medicine as a cancer treatment: modern perspectives of ancient but advanced science. Cancer Med, 8(5):1958-1975.

[34]YanBQ, WangDS, DongSW, et al., 2017. Palmatine inhibits TRIF-dependent NF-‍κB pathway against inflammation induced by LPS in goat endometrial epithelial cells. Int Immunopharmacol, 45:194-200.

[35]YeZH, NingK, AnderBP, et al., 2020. Therapeutic effect of methane and its mechanism in disease treatment. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 21(8):593-602.

[36]YiL, ZhouZD, ZhengYJ, et al., 2019. Suppressive effects of GSS on lipopolysaccharide-induced endothelial cell injury and ALI via TNF-‍αand IL-6. Mediat Inflamm, 2019:4251394.

[37]YuML, QiBQ, WuXX, et al., 2017. Baicalein increases cisplatin sensitivity of A549 lung adenocarcinoma cells via PI3K/Akt/NF-‍κB pathway. Biomed Pharmacother, 90:677-685.

[38]ZeytunA, ChaudharyA, PardingtonP, et al., 2010. Induction of cytokines and chemokines by Toll-like receptor signaling: strategies for control of infammation. Crit Rev Immunol, 30(1):53-67.

[39]ZhangH, WuZM, YangYP, et al., 2019. Catalpol ameliorates LPS-induced endometritis by inhibiting inflammation and TLR4/NF-‍κB signaling. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 20(10):816-827.

[40]ZhaoK, YangCX, LiP, et al., 2020. Epigenetic role of N6-methyladenosine (m6A) RNA methylation in the cardiovascular system. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 21(7):509-523.

[41]ZhengWH, ChenCH, ZhangCX, et al., 2018. The protective effect of phloretin in osteoarthritis: an in vitro and in vivo study. Food Funct, 9(1):263-278.

[42]ZilberbergMD, EpsteinSK, 1998. Acute lung injury in the medical ICU: comorbid conditions, age, etiology, and hospital outcome. Am J Respir Crit Care Med, 157(4 Pt 1):1159-1164.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2022 Journal of Zhejiang University-SCIENCE