Abstract
Influenza causes respiratory infections and poses health risks to humans and animals; its effects are complicated by increasing resistance to existing anti-influenza viral agents. Therefore, novel therapeutic approaches against influenza virus infection are required. Psoraleae semen has been widely used in traditional medicine in Korea, Taiwan, China, and Japan for treating and preventing various diseases. In this study, we examined the anti-viral activities and mechanism of action of the water extract of Psoraleae semen (WPS) using RAW 264.7 and MDCK cells. We found that pre- and post-treatment with 100 μg/mL WPS markedly inhibited influenza A virus replication as assessed using a green fluorescent protein reporter virus, reduced viral protein expression (NS-1, PA, HA, PB-1, M1, and M2), and inhibited NA and HA activities. Mechanism studies revealed that WPS induced type I interferon cytokine secretion and subsequent stimulation of an anti-viral state in RAW 264.7 cells. Further, WPS exerted inhibitory effects on neuraminidase in influenza virus strains H1N1 and H3N2. Meanwhile, WPS exhibited inhibitory effects on hemagglutination in H3N2 but not in H1N1. Based on these results, WPS serves as an immunomodulator and inhibitor of influenza hemagglutinin and neuraminidase. Our results suggest that WPS is a promising source of novel anti-influenza drug candidates.
Highlights
Influenza viruses belong to the Orthomyxoviridae family
The results illustrated that water extract of Psoraleae semen (WPS) concentrations of ≤400 μg/mL had no significant effects on cell viability, indicating that WPS was not toxic to RAW 264.7 and MDCK cells (Figures 1A,B)
We found that viral supernatant titers of H1N1-green fluorescent protein (GFP), IFN-beta/H1N1-GFP, and WPS/H1N1GFP-infected cells were significantly reduced by WPS or IFN-β treatment (0 hemagglutination units (HAUs)) compared to that in the virus-only group (64 HAUs; Figure 2D)
Summary
Influenza viruses belong to the Orthomyxoviridae family. There are three types of influenza viruses: A, B, and C (Zambon, 1999). Infection by type B and C viruses is mainly restricted to humans (Capua and Alexander, 2004). Vaccines represent the most effective strategy for controlling influenza virus infection, but influenza vaccines have disadvantages, including inadequate protection, high cost, difficulty in predicting representative strains, and time requirements for design and production (Hayden, 2006; Fiore et al, 2009). High resistance levels have been reported for adamantanes against IAV, and Psoraleae Semen against Influenza Virus these drugs are ineffective against influenza B virus (Centers for Disease and Prevention, 2006; Ison, 2011). Numerous reports have illustrated that IAVs develop resistance to oseltamivir, zanamivir and peramivir (Centers for Disease and Prevention, 2006; Bouvier et al, 2008; Hurt et al, 2009). There is a critical need to develop novel anti-influenza drugs to control and prevent future influenza pandemics and epidemics
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