Effect of aloin on viral neuraminidase and hemagglutinin-specific T cell immunity in acute influenza

Ching Tai Huang, Chen Yiu Hung, Yu Chia Hseih, Chia Shiang Chang, Arul Balaji Velu, Yueh Chia He, Yu Lin Huang, Ting An Chen, Tse Ching Chen, Chun Yen Lin, Yung Chang Lin, Shin Ru Shih, Avijit Dutta*

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

36 引文 斯高帕斯(Scopus)

摘要

Background: Millions of people are infected by the influenza virus worldwide every year. Current selections of anti-influenza agents are limited and their effectiveness and drug resistance are still of concern. Purpose: Investigation on in vitro and in vivo effect of aloin from Aloe vera leaves against influenza virus infection. Methods: In vitro antiviral property of aloin was measured by plaque reduction assay in which MDCK cells were infected with oseltamivir-sensitive A(H1N1)pdm09, oseltamivir-resistant A(H1N1)pdm09, H1N1 or H3N2 influenza A or with influenza B viruses in the presence of aloin. In vivo activity was tested in H1N1 influenza virus infected mice. Aloin-mediated inhibition of influenza neuraminidase activity was tested by MUNANA assay. Aloin treatment-mediated modulation of anti-influenza immunity was tested by the study of hemagglutinin-specific T cells in vivo. Results: Aloin significantly reduced in vitro infection by all the tested strains of influenza viruses, including oseltamivir-resistant A(H1N1)pdm09 influenza viruses, with an average IC50 value 91.83 ± 18.97 μM. In H1N1 influenza virus infected mice, aloin treatment (intraperitoneal, once daily for 5 days) reduced virus load in the lungs and attenuated body weight loss and mortality. Adjuvant aloin treatment also improved the outcome with delayed oseltamivir treatment. Aloin inhibited viral neuraminidase and impeded neuraminidase-mediated TGF-β activation. Viral neuraminidase mediated immune suppression with TGF-β was constrained and influenza hemagglutinin-specific T cell immunity was increased. There was more infiltration of hemagglutinin-specific CD4+ and CD8+ T cells in the lungs and their production of effector cytokines IFN-γ and TNF-α was boosted. Conclusion: Aloin from Aloe vera leaves is a potent anti-influenza compound that inhibits viral neuraminidase activity, even of the oseltamivir-resistant influenza virus. With suppression of this virus machinery, aloin boosts host immunity with augmented hemagglutinin-specific T cell response to the infection. In addition, in the context of compromised benefit with delayed oseltamivir treatment, adjuvant aloin treatment ameliorates the disease and improves survival. Taken together, aloin has the potential to be further evaluated for clinical applications in human influenza.

原文英語
文章編號152904
期刊Phytomedicine
64
DOIs
出版狀態已出版 - 11 2019

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© 2019 Elsevier GmbH

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