In vitro and in vivo anti-influenza virus activities of flavonoids and related compounds as components of Brazilian propolis (AF-08)

We previously demonstrated that Brazilian propolis AF-08 exhibits anti-influenza virus activity in vitro and in vivo. To characterize its effective components, flavonoids and related compounds involved in AF-08 were examined for their anti-influenza virus activity in vitro and in vivo. Four flavonoids and three phenyl propanoids were selected as possible components of AF-08 by HPLC. Among them, apigenin, kaempferol, and coumaric acid exhibited significant antiviral activity against oseltamivir- and peramivir-sensitive and oseltamivir- and peramivir-resistant influenza viruses in plaque reduction assays and kaempferol did not interfere with virus adsorption and/or invasion in vitro. The oral administration of kaempferol was significantly effective in prolonging survival times and reducing virus titers in bronchoalveolar lavage fluids prepared from influenza virus-infected mice. Thus, kaempferol, a component of AF-08, exhibited therapeutic efficacy in limiting influenza symptoms in mice and is indicated to contribute to the in vivo anti-influenza virus activity of propolis AF-08 as a crude extract.