tetano
Editor, Senior Moderator
Oncotarget. 2015 Dec 2. doi: 10.18632/oncotarget.6448. [Epub ahead of print]
[h=1]Saikosaponin a inhibits influenza A virus replication and lung immunopathology.[/h] Chen J[SUP]1[/SUP], Duan M[SUP]2[/SUP], Zhao Y[SUP]1,[/SUP][SUP]3[/SUP], Ling F[SUP]1[/SUP], Xiao K[SUP]2[/SUP], Li Q[SUP]2[/SUP], Li B[SUP]2,[/SUP][SUP]4[/SUP], Lu C[SUP]2[/SUP], Qi W[SUP]1[/SUP], Zeng Z[SUP]1[/SUP], Liao M[SUP]1[/SUP], Liu Y[SUP]1[/SUP], Chen W[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] 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]
[h=1]Saikosaponin a inhibits influenza A virus replication and lung immunopathology.[/h] Chen J[SUP]1[/SUP], Duan M[SUP]2[/SUP], Zhao Y[SUP]1,[/SUP][SUP]3[/SUP], Ling F[SUP]1[/SUP], Xiao K[SUP]2[/SUP], Li Q[SUP]2[/SUP], Li B[SUP]2,[/SUP][SUP]4[/SUP], Lu C[SUP]2[/SUP], Qi W[SUP]1[/SUP], Zeng Z[SUP]1[/SUP], Liao M[SUP]1[/SUP], Liu Y[SUP]1[/SUP], Chen W[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] 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]