Oncotarget

Research Papers: Immunology:

Saikosaponin A inhibits influenza A virus replication and lung immunopathology

Jianxin Chen, Mubing Duan, Yaqin Zhao, Fangfang Ling, Kun Xiao, Qian Li, Bin Li, Chunni Lu, Wenbao Qi, Zhenling Zeng, Ming Liao, Yahong Liu and Weisan Chen _

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Oncotarget. 2015; 6:42541-42556. https://doi.org/10.18632/oncotarget.6448

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Abstract

Jianxin Chen1,*, Mubing Duan2,*, Yaqin Zhao1,4, Fangfang Ling1, Kun Xiao2, Qian Li2, Bin Li2,3, Chunni Lu2, Wenbao Qi1, Zhenling Zeng1, Ming Liao1, Yahong Liu1 and Weisan Chen2

1 Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China

2 Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia

3 National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, China

4 Present address: Xinjiang Institute of Chinese Materia Medica and Ethnic Materia Medica, Urumqi, Xinjiang, China

* These authors have contributed equally to this work as first authors

Correspondence to:

Jianxin Chen, email:

Weisan Chen, email:

Keywords: Saikosaponin A, anti-inflammatory agent, influenza A virus, PR8, X-31, Immunology and Microbiology Section, Immune response, Immunity

Received: July 05, 2015 Accepted: November 22, 2015 Published: December 02, 2015

Abstract

Fatal influenza outcomes result from a combination of rapid virus replication and collateral lung tissue damage caused by exaggerated pro-inflammatory host immune cell responses. There are few therapeutic agents that target both biological processes for the attenuation of influenza-induced lung pathology. We show that Saikosaponin A, a bioactive triterpene saponin with previouslyestablished anti-inflammatory effects, demonstrates both in vitro and in vivo anti-viral activity against influenza A virus infections. Saikosaponin A attenuated the replication of three different influenza A virus strains, including a highly pathogenic H5N1 strain, in human alveolar epithelial A549 cells. This anti-viral activity occurred through both downregulation of NF-κB signaling and caspase 3-dependent virus ribonucleoprotein nuclear export as demonstrated by NF-κB subunit p65 and influenza virus nucleoprotein nuclear translocation studies in influenza virus infected A549 cells. Critically, Saikosaponin A also attenuated viral replication, aberrant pro-inflammatory cytokine production and lung histopathology in the widely established H1N1 PR8 model of influenza A virus lethality in C57BL/6 mice. Flow cytometry studies of mouse bronchoalveolar lavage cells revealed that SSa exerted immunomodulatory effects through a selective attenuation of lung neutrophil and monocyte recruitment during the early peak of the innate immune response to PR8 infection. Altogether, our results indicate that Saikosaponin A possesses novel therapeutic potential for the treatment of pathological influenza virus infections.


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