5-7-4--trihydroxy-8-methoxyflavone and Orthomyxoviridae-Infections

Enhancement of in vivo antiviral activity of 5,7,4'-trihydroxy-8-methoxyflavone (F36) against H3N2 subtype of influenza A virus by drug delivery system (DDS) with hydroxypropyl cellulose (HPC) was studied. Although in the absence of HPC F36 (0.5 mg/kg) showed no antiviral activity against mouse-adapted influenza virus A/Guizhou/54/89 (H3N2) in mice, when F36 solution containing HPC was administered intranasally 5 min after the virus inoculation, proliferation of the virus in both nasal and broncho-alveolar cavities was inhibited significantly. The relationship between concentration (0.2-0.5%) and deposition ratio of HPC was studied. When 10 microliters of fluorescein isothiocyanate (FITC)-conjugated HPC solution was administered intranasally to BALB/c mice, deposition ratio of HPC at 6 h after inoculation in nasal cavity was dependent on its concentration. The deposition ratio of HPC in broncho-alveolar cavity, however, was reversely dependent on its concentration. Anti-influenza virus activity of F36 in nasal and broncho-alveolar cavities was dependent both on the concentration and deposition ratio of HPC. HPC was most effective at 0.5% in nasal cavity and at 0.3% in broncho-alveolar cavity. These results indicate that DDS with HPC enhances the anti-influenza virus activity of F36 in vivo.

Topics: Administration, Intranasal; Animals; Antiviral Agents; Cellulose; Drug Delivery Systems; Female; Flavonoids; Influenza A virus; Lung; Mice; Mice, Inbred BALB C; Nasal Cavity; Orthomyxoviridae Infections; Virus Replication; Viscosity

When mouse-adapted influenza virus A/PR/8/34 (A/PR8) (10 PFU/cell) was adsorbed to Madin-Darby canine kidney (MDCK) cells at 4 degrees C for 1 h and incubated at 37 degrees C, release of the virus from the cells was detected in the medium from 4 h after incubation and reached to plateau at 8 h. However, 5,7,4'-trihydroxy-8-methoxyflavone (F36) from the roots of Scutellaria baicalensis significantly reduced this single-cycle replication of A/PR8 from 4 h to 12 h after incubation by dose-dependent manner and the dose which decrease the virus titer one tenth was 11 microM. F36 (50 microM) did not inhibit the adsorption of A/PR8 to MDCK cells, but reduced release of the virus in the medium, when it was added at 0 or 2 h after the incubation. The cell-associated virus determined by sialidase activity was also reduced by F36 treatment at 0 or 2 h. F36 also inhibited the fusion of A/PR8 with liposomes containing bovine brain mixed gangliosides at pH 5.0. However, F36 little affected on the elongation activity of the viral RNA-dependent RNA polymerase in vitro. These results suggest that F36 reduces the replication of A/PR8 by inhibiting the fusion of the virus with endosome/lysosome membrane which occurs at early stage of virus infection cycle. Whereas, when F36 was added to the MDCK cells infected with A/PR8 at 3 or 4 h after incubation, release of the virus in the medium was reduced but the cell-associated virus was increased in comparison with control.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Antigens, Viral; Antiviral Agents; Cells, Cultured; Dogs; Flavonoids; Fluorescent Antibody Technique; Influenza A virus; Kidney; Mice; Microscopy, Electron, Scanning; Neuraminidase; Orthomyxoviridae Infections; Plant Extracts; Plant Roots; Plants, Medicinal; Viral Proteins; Virus Replication