Effects of maoto (ma-huang-tang) on transcriptome signature in influenza virus infection

We evaluated the effects of maoto, a traditional kampo medicine, as a herbal multi-compound medicine on host transcriptome responses in a mouse model of influenza infection. On the fifth day of oral administration to mice intranasally infected with influenza virus (A/PR/8/34 (H1N1), maoto significantly improved survival rate, decreased viral titer, and ameliorated the infection-induced phenotype as compared with control mice. Analysis of the lung and plasma transcriptome profile showed that maoto significantly up-regulated the expression of macrophage- and T-cell-related genes. Collectively, these results suggest that maoto regulates the host’s inflammatory response. Materials Maoto was dissolved in distilled water before administration to mice. Mouse-adapted influenza virus (A/PR/8/34(H1N1)) (PR8) was used to infect mice. Virus culture The influenza virus was cultured in Madin–Darby canine kidney (MDCK) cells, and PR8 collected from the culture medium was used for intranasal inoculation of mice. Animals Female BALB/c Cr Slc mice purchased from Japan SLC, Inc. (Shizuoka, Japan) were used from 6 weeks of age after habituation. In vivo influenza virus inoculation Influenza virus (1x10^5　PFU/0.05 mL/mouse) was administered by intranasal inoculation. Maoto (2 g/10mL/kg) was orally administered for 5 days starting 1 hour after inoculation. Mice with no inoculation were used as control mice against the infection, and infected mice that were treated distilled water were used as infected control mice. In total, there were three groups of mice: 1) no-inoculation (NI) group; 2) influenza virus inoculation (IVI) control group; 3) IVI with MT 2 g/10mL/kg treatment (IVI+MT) group. Ten mice from each of the three mouse groups were used to collect lung tissue at 5 day post inoculation (dpi). In the result, the number of surviving mice in each group was 10/10(NI), 4/10 (IVI) and 9/10 (IVI+MT) at 5 dpi, and the lung tissue sample from these mice were used for transcriptome analysis.