1. Academic Validation
  2. Antiviral activity of aloe-emodin against influenza A virus via galectin-3 up-regulation

Antiviral activity of aloe-emodin against influenza A virus via galectin-3 up-regulation

  • Eur J Pharmacol. 2014 Sep 5;738:125-32. doi: 10.1016/j.ejphar.2014.05.028.
Shih-Wen Li 1 Tsuey-Ching Yang 2 Chien-Chen Lai 3 Su-Hua Huang 4 Jun-Ming Liao 1 Lei Wan 5 Ying-Ju Lin 5 Cheng-Wen Lin 6
Affiliations

Affiliations

  • 1 Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 404, Taiwan.
  • 2 Department of Biotechnology and Laboratory Science in Medicine, National Yang Ming University, Taipei, Taiwan.
  • 3 Institute of Molecular Biology, National Chung Hsing University, Taichung 402, Taiwan.
  • 4 Department of Biotechnology and Bioinformatics, Asia University, Taichung 413, Taiwan.
  • 5 Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung 404, Taiwan.
  • 6 Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 404, Taiwan; Department of Biotechnology and Bioinformatics, Asia University, Taichung 413, Taiwan. Electronic address: cwlin@mail.cmu.edu.tw.
Abstract

Novel influenza A H7N9 virus, which emerged in 2013, and highly pathogenic H5N1 virus, identified since 2003, pose challenges to public health and necessitate quest for new anti-influenza compounds. Anthraquinone derivatives like aloe-emodin, emodin and chrysophanol, reportedly exhibit Antiviral activity. This study probes their inhibitory mechanism and effect against influenza A virus. Of three anthraquinone derivatives, aloe-emodin, with a lower cytotoxicity showed concentration-dependently reducing virus-induced cytopathic effect and inhibiting replication of influenza A in MDCK cells. 50% inhibitory concentration value of aloe-emodin on virus yield was less than 0.05 μg/ml. Proteomics and Western blot of MDCK cells indicated aloe-emodin up-regulating Galectin-3, and thioredoxin as well as down-regulating nucleoside diphosphate kinase A. Western blot and quantitative PCR confirmed aloe-emodin up-regulating Galectin-3 expression; recombinant Galectin-3 augmented expression of Antiviral genes IFN-β, IFN-γ, PKR and 2'5',-OAS in infected cells, agreeing with expression pattern of those treated with aloe-emodin. Galectin-3 also inhibited influenza A virus replication. Proteomic analysis of treated cells indicated Galectin-3 up-regulation as one anti-influenza A virus action by aloe-emodin. Since Galectin-3 exhibited cytokine-like regulatory actions via JAK/STAT pathways, aloe-emodin also restored NS1-inhibited STAT1-mediated Antiviral responses in transfected cells: e.g., STAT1 phosphorylation of interferon (IFN) stimulation response element (ISRE)-driven promoter, RNA-dependent protein kinase (PKR) and 2'5',-oligoadenylate synthetase (2'5',-OAS) expression. Treatment with aloe-emodin could control influenza Infection in humans.

Keywords

Aloe-emodin; Anthraquinone; Galectin-3; Influenza A virus.

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