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Oncotarget. 2015 Dec 2. doi: 10.18632/oncotarget.6448. [Epub ahead of print]
Saikosaponin a inhibits influenza A virus replication and lung immunopathology.
Chen J1, Duan M2, Zhao Y1,3, Ling F1, Xiao K2, Li Q2, Li B2,4, Lu C2, Qi W1, Zeng Z1, Liao M1, Liu Y1, Chen W2.
Author information
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.
KEYWORDS:
Immune response; Immunity; Immunology and Microbiology Section; PR8; X-31; anti-inflammatory agent; influenza A virus; saikosaponin A
PMID: 26637810 [PubMed - as supplied by publisher]
Saikosaponin a inhibits influenza A virus replication and lung immunopathology.
Chen J1, Duan M2, Zhao Y1,3, Ling F1, Xiao K2, Li Q2, Li B2,4, Lu C2, Qi W1, Zeng Z1, Liao M1, Liu Y1, Chen W2.
Author information
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.
KEYWORDS:
Immune response; Immunity; Immunology and Microbiology Section; PR8; X-31; anti-inflammatory agent; influenza A virus; saikosaponin A
PMID: 26637810 [PubMed - as supplied by publisher]