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We investigated effects of isoscutellarein-8-methylether (5,7,4'-trihydroxy-8-methoxyflavone, F36) from the roots of Scutellaria baicalensis on the single-cycle replication of mouse-adapted influenza viruses A/Guizhou/54/89 (H3N2 subtype) and B/Ibaraki/2/85 in Madin-Darby canine kidney (MDCK) cells. The agent suppressed replication of these viruses from 6 to 12 h after incubation in a dose-dependent manner by 50% at 20 microM and 90% at 40 microM, respectively. F36 (50 microM) reduced the release of B/Ibaraki virus in the medium by 90-93% when it was added to the MDCK cells at 0 to 4 h after incubation. The cell-associated virus determined by sialidase activity was also reduced by the treatment at 0 to 4 h. F36 (120 microM) inhibited the low pH-dependent membrane fusion of both the viruses with the liposome containing mixed gangliosides from bovine brain. However, the agent little affected the hemagglutination and RNA-dependent RNA polymerase activities of these viruses in vitro. These results suggest that F36 inhibits the replication of A/Guizhou and B/Ibaraki viruses at least partly by inhibiting the fusion of viral envelopes with the endosome/lysosome membrane which occurs at the early stage of the virus infection cycle. F36 (0.5 mg/kg) showed no antiviral activity against A/Guizhou and B/Ibaraki viruses in mice when administered intranasally 5 min prior to virus inoculation, whereas it significantly inhibited their proliferation in the mouse lung when administered intranasally 7 times (total 3.5 mg/kg) from 18 h before to 54 h after virus infection.

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Antiviral Activity of Plant Flavonoid, 5,7,4'-Trihydroxy-8-methoxyflavone, from the Roots of Scutellaria baicalensis against Influenza A (H3N2) and B Viruses.