Rosmarinic acid interferes with influenza virus A entry and replication by decreasing GSK3β and phosphorylated AKT expression levels

Jia Rong Jheng, Chung Fan Hsieh, Yu Hsiu Chang, Jin Yuan Ho, Wen Fang Tang, Zi Yi Chen, Chien Jou Liu, Ta Jen Lin, Li Yu Huang, Jyh Haur Chern, Jim Tong Horng*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Background: The purpose of this study was to examine the in vivo activity of rosmarinic acid (RA) – a phytochemical with antioxidant, anti-inflammatory, and antiviral properties – against influenza virus (IAV). An antibody-based kinase array and different in vitro functional assays were also applied to identify the mechanistic underpinnings by which RA may exert its anti-IAV activity. Methods: We initially examined the potential efficacy of RA using an in vivo mouse model. A time-of-addition assay and an antibody-based kinase array were subsequently applied to investigate mechanism-of-action targets for RA. The hemagglutination inhibition assay, neuraminidase inhibition assay, and cellular entry assay were also performed. Results: RA increased survival and prevented body weight loss in IAV-infected mice. In vitro experiments revealed that RA inhibited different IAV viruses – including oseltamivir-resistant strains. From a mechanistic point of view, RA downregulated the GSK3β and Akt signaling pathways – which are known to facilitate IAV entry and replication into host cells. Conclusions: RA has promising preclinical efficacy against IAV, primarily by interfering with the GSK3β and Akt signaling pathways.

Original languageEnglish
Pages (from-to)598-610
Number of pages13
JournalJournal of Microbiology, Immunology and Infection
Volume55
Issue number4
DOIs
Publication statusPublished - Aug 2022
Externally publishedYes

Keywords

  • Akt
  • GSK3β
  • Influenza virus A
  • Rosmarinic acid
  • Signaling pathways

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