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 language | English |
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Pages (from-to) | 598-610 |
Number of pages | 13 |
Journal | Journal of Microbiology, Immunology and Infection |
Volume | 55 |
Issue number | 4 |
DOIs | |
Publication status | Published - Aug 2022 |
Externally published | Yes |
Keywords
- Akt
- GSK3β
- Influenza virus A
- Rosmarinic acid
- Signaling pathways