Protective Effect of Pudilan Xiaoyan Oral Liquid (Pdl) on Influenza Viral Pneumonia by Regulating Tlr3/Myd88 Signaling Pathway

Ethnopharmacological relevance: Pudilan Xiaoyan Oral Liquid (PDL) as a famous Chinese patent medicine has been widely used for treating inflammatory diseases. However, the antiviral effect of PDL remain unclear. Here, the in vitro and in vivo antiviral effect of PDL against influenza A virus and their potential mechanisms were for the first time investigated.Materials and methods: The in vitro broad-spectrum antiviral activity of PDL against influenza A virus was investigated using MDCK cell model. The in vivo protective effect on influenza viral pneumonia was evaluated with the ICR female mice infected by influenza A virus. Moreover, the inhibitory effect on inflammatory cytokines including TNF-α, IP10, IL-10, IL-6 and IFN-γ in lung tissue were measured by qRT-PCR. The underlying mechanism of PDL against influenza viral pneumonia in vitro and in vivo was investigated by RT-PCR or Western blot.Results: Our results indicated that in vitro PDL exhibited a good broad-spectrum inhibitory effect on different subtypes of influenza A viruses and in vivo PDL could dose-dependently prevent weight loss of mice, increase food intake and reduce mortality caused by influenza A H1N1 virus. Furthermore, PDL could markedly improve the acute lung injury and significantly reduce the mRNA levels of inflammatory factors such as TNF-α, IP10, IL-10, IL-1β, IL-6, and IFN-γ. Mechanistic research indicated that the protective effect of PDL on viral pneumonia might be achieved by inhibiting TLR3/MyD88/IRAK4/TRAF3 signaling pathway.Conclusion: PDL not only showed a good inhibitory effect on influenza A virus in vitro , but also exhibited a significant protective effect against lethal influenza virus infection in vivo . Our findings will provide a new option for clinical treatment of influenza virus pneumonia.