Tiliroside, a Polymerase Inhibitor from Hibiscus Mutabilis L., Exhibits Anti-Influenza Activity in Vitro and in Vivo

Ethnopharmacological relevance: Fu Rong Ye (FRY), the leaf of Hibiscus Mutabilis L., is a Chinese medicinal herb used to treat coughs and respiratory diseases. FRY is the major herbal component of the patent medicine Fupo Ganmao Granules as a treatment for the common cold. However, its anti-influenza active components and mechanism were not identified.Aim: Here, we aim to a) explain FRY aqueous extract inhibited influenza A virus (IAV), b) isolate the anti-influenza phytochemicals from GLY extract and c) explore its anti-flu mechanism.Material and methods: Bioassay guided isolation was performed to get anti-flu component. Influenza infected cell and mouse model were used for efficacy evaluation.Results: Using bioassay-guided isolation, the flavonoid tiliroside was obtained, which inhibited four IAV strains in MDCK cells with EC 50 ranging from 3.87~27.61μM by suppressing the viral ribonucleoprotein activity. Tiliroside also significantly downregulated the expression of cytokines/chemokines in A549 cells, and protected 50% of PR8-infected BALB/c mice from death and improved lung edema conditions at 800mg/kg/d.Conclusion: Tiliroside is effective for influenza infection treatment and promising for further drug development. This study is the first to demonstrate that tiliroside in FRY acts against influenza virus.