In vitro and in vivo anti-influenza virus activity of diarylheptanoids isolatedfrom Alpinia officinarum.

摘要

BACKGROUND: Diarylheptanoids (AO-0002[7-(4''-hydroxy-3''-methoxyphenyl)-1-phenyl-4E-hepten-3-one] and AO-0011[(5S)-5-hydroxy-7-(4''-hydroxyphenyl)-1-phenyl-3-heptanone]) isolated fromAlpinia officinarum have been reported to exhibit anti-influenza virus activityin vitro. Hence, efficacies against influenza virus infection and the mode ofantiviral action were evaluated in vivo and in vitro, respectively.METHODS: In a murine influenza virus infection model, diarylheptanoids wereorally administered three times daily to mice infected with influenza A/PR/8/34virus for 6 days after infection. AO-0002 was examined for its antiviral activityagainst the wild types of influenza viruses A/PR/8/34 (H1N1),oseltamivir-resistant A/PR/8/34 (H1N1), A/Bangkok/93/03 (H1N1), A/Ishikawa/7/82(H3N2), A/Fukushima/13/43 (H3N2), B/Singapore/222/79 and B/Fukushima/15/93 inplaque reduction or yield reduction assays. The mode of anti-influenza virusaction was assessed by a virus adsorption assay, immunofluorescence assay ofviral antigens, and inhibition of viral messenger RNA synthesis using real-timereverse transcriptase PCR.RESULTS: AO-0002 at 100 mg/kg was significantly effective in reducing the bodyweight loss and prolonging survival times of infected mice without toxicity, butAO-0011 was not. AO-0002 at 30 and 100 mg/kg significantly reduced virus titresin bronchoalveolar lavage fluids of the lungs on days 3 and 6 after infection.AO-0002 exhibited anti-influenza virus activity against all viruses used,including the oseltamivir-resistant strain in vitro. The compound had no effecton virus adsorption or invasion into cells, but dose-dependently suppressed theexpression of viral messenger RNA and antigens.CONCLUSIONS: AO-0002 was suggested to have a different anti-influenza virusaction to that of oseltamivir and was verified to show anti-influenza activity invitro and in vivo.