Jheng, Jia-RongHsieh, Chung-FanChang, Yu-HsiuHo, Jin-YuanTang, Wen-FangChen, Zi-YiLiu, Chien-JouLin, Ta-JenHuang, Li-YuChern, Jyh-HaurHorng, Jim-Tong2025-01-302025-01-302022Jheng JR, Hsieh CF, Chang YH, et al. Rosmarinic acid interferes with influenza virus A entry and replication by decreasing GSK3β and phosphorylated AKT expression levels. J Microbiol Immunol Infect. 2022;55(4):598-610. doi:10.1016/j.jmii.2022.04.012https://hdl.handle.net/1805/45609Background: 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.en-USAttribution-NonCommercial-NoDerivatives 4.0 InternationalAktGSK3βInfluenza virus ARosmarinic acidSignaling pathwaysArticle