Andrographolide inhibits influenza A virus-induced inflammation in a murine model through NF-κB and JAK-STAT signaling pathway

被引:98
作者
Ding, Yi [1 ]
Chen, Lizhu [1 ]
Wu, Wenjiao [1 ]
Yang, Jie [1 ]
Yang, Zifeng [2 ]
Liu, Shuwen [1 ,3 ]
机构
[1] Southern Med Univ, Guangzhou Key Lab Drug Res Emerging Virus Prevent, Guangdong Prov Key Lab New Drug Screening, Sch Pharmaceut Sci, Guangzhou, Guangdong, Peoples R China
[2] Guangzhou Med Univ, State Key Lab Resp Dis, Guangzhou Inst Resp Dis, Natl Clin Ctr Resp Dis,Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China
[3] Southern Med Univ, Guangdong Prov Inst Nephrol, State Key Lab Organ Failure Res, Guangzhou, Guangdong, Peoples R China
关键词
Andrographolide; Influenza viruses; Immunomodulator; Virus entry inhibitor; NF-kappa B; JAK-STAT signaling pathway; PROTECTS MICE; LUNG INJURY; INFECTION; ACTIVATION; ENTRY; PATHOGENESIS; PROPAGATION; INTERFERONS; HOMEOSTASIS; RESISTANCE;
D O I
10.1016/j.micinf.2017.08.009
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Influenza viruses, the main cause of respiratory tract diseases, cause high morbidity and mortality in humans. Excessive inflammation in the lungs is proposed to be a hallmark for the severe influenza virus infection, especially influenza A virus infection. Strategies against inflammation induced by influenza A virus infection could be a potential anti-influenza therapy. Here, lethal dose of mouse-adapted H1N1 strain PR8A/PR/8/34 was inoculated C57BL/6 mice to detect the anti-influenza activity of andrographolide, the active component of traditional Chinese medicinal herb Andrographis paniculata, with or without influenza virus entry inhibitor CL-385319. Treatment was initiated on 4 days after infection. The survival rate, body weight, lung pathology, viral loads, cytokine expression were monitored in 14 days post inoculation. The combination group had the highest survival rate. Andrographolide treatment could increase the survival rate, diminish lung pathology, decrease the virus loads and the inflammatory cytokines expression induced by infection. Mechanism studies showed the NF-kappa B and JAK-STAT signaling pathway were involved in the activity of andrographolide. In conclusion, combination of virus entry inhibitor with immunomodulator might be a promising therapeutic approach for influenza. (C) 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:605 / 615
页数:11
相关论文
共 44 条
[1]   Structures of influenza A proteins and insights into antiviral drug targets [J].
Das, Kalyan ;
Aramini, James M. ;
Ma, Li-Chung ;
Krug, Robert M. ;
Arnold, Eddy .
NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2010, 17 (05) :530-538
[2]   Alveolar macrophages and type I IFN in airway homeostasis and immunity [J].
Divangahi, Maziar ;
King, Irah L. ;
Pernet, Erwan .
TRENDS IN IMMUNOLOGY, 2015, 36 (05) :307-314
[3]   Role of Hypercytokinemia in NF-κB p50-Deficient Mice after H5N1 Influenza A Virus Infection [J].
Droebner, Karoline ;
Reiling, Sarah Julia ;
Planz, Oliver .
JOURNAL OF VIROLOGY, 2008, 82 (22) :11461-11466
[4]   The NF-B inhibitor SC75741 efficiently blocks influenza virus propagation and confers a high barrier for development of viral resistance [J].
Ehrhardt, Christina ;
Rueckle, Andrea ;
Hrincius, Eike R. ;
Haasbach, Emanuel ;
Anhlan, Darisuren ;
Ahmann, Katharina ;
Banning, Carina ;
Reiling, Sarah J. ;
Kuehn, Joachim ;
Strobl, Stefan ;
Vitt, Daniel ;
Leban, Johann ;
Planz, Oliver ;
Ludwig, Stephan .
CELLULAR MICROBIOLOGY, 2013, 15 (07) :1198-1211
[5]   Interferons and viral infections [J].
Fensterl, Volker ;
Sen, Ganes C. .
BIOFACTORS, 2009, 35 (01) :14-20
[6]   Viral Inhibition of the IFN-Induced JAK/STAT Signalling Pathway: Development of Live Attenuated Vaccines by Mutation of Viral-Encoded IFN-Antagonists [J].
Fleming, Stephen B. .
VACCINES, 2016, 4 (03)
[7]   Prevention of Influenza Virus-Induced Immunopathology by TGF-β Produced during Allergic Asthma [J].
Furuya, Yoichi ;
Furuya, Andrea K. M. ;
Roberts, Sean ;
Sanfilippo, Alan M. ;
Salmon, Sharon L. ;
Metzger, Dennis W. .
PLOS PATHOGENS, 2015, 11 (09)
[8]   Broad-spectrum antiviral properties of andrographolide [J].
Gupta, Swati ;
Mishra, K. P. ;
Ganju, Lilly .
ARCHIVES OF VIROLOGY, 2017, 162 (03) :611-623
[9]   The NF-kappaB inhibitor SC75741 protects mice against highly pathogenic avian influenza A virus [J].
Haasbach, Emanuel ;
Reiling, Sarah Julia ;
Ehrhardt, Christina ;
Droebner, Karoline ;
Rueckle, Andrea ;
Hrincius, Eike R. ;
Leban, Johann ;
Strobl, Stefan ;
VittD, Daniel ;
Ludwig, Stephan ;
Planz, Oliver .
ANTIVIRAL RESEARCH, 2013, 99 (03) :336-344
[10]   Intranasal application of polyethyleneimine suppresses influenza virus infection in mice [J].
He, Biao ;
Fu, Yuhong ;
Xia, Shuai ;
Yu, Fei ;
Wang, Qian ;
Lu, Lu ;
Jiang, Shibo .
EMERGING MICROBES & INFECTIONS, 2016, 5