Journal
ONCOTARGET
Volume 6, Issue 40, Pages 42541-42556Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.6448
Keywords
saikosaponin A; anti-inflammatory agent; influenza A virus; PR8; X-31; Immunology and Microbiology Section; Immune response; Immunity
Categories
Funding
- National Health and Medical Research Council, Australia [1071916]
- Chinese Program for Changjiang Scholars and Innovative Research Team in University [IRT13063]
- Scientific and Technological Project Grant of Guangdong Province [2013B020224005]
- National Natural Science Foundation Grant, China [31572565, 30972217]
- Natural Science Foundation of Guangdong Province [2015A030313399]
Ask authors/readers for more resources
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 previously established 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-kappa B signaling and caspase 3-dependent virus ribonucleoprotein nuclear export as demonstrated by NF-kappa B 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available