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

Akinori Nishi,Hiroaki Kitano,Seiichi Iizuka,Masahiro Yamamoto,Haruo Kuroki,Chika Shimobori,Shigeki Nabeshima,Katsuya Ohbuchi,Ayako Yachie,Keisuke Ogura,Noriko Kaifuchi,Yukiko Matsuoka,Aiko Sugiyama

doi:10.1038/s41598-021-82707-1

Abstract

Maoto, a traditional kampo medicine, has been clinically prescribed for influenza infection and is reported to relieve symptoms and tissue damage. In this study, we evaluated the effects of maoto as an herbal multi-compound medicine on host 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 and lipid mediator metabolite profile showed that maoto altered the profile of lipid mediators derived from ω-6 and ω-3 fatty acids to restore a normal state, and significantly up-regulated the expression of macrophage- and T-cell-related genes. Collectively, these results suggest that maoto regulates the host’s inflammatory response by altering the lipid mediator profile and thereby ameliorating the symptoms of influenza.

Highlights

Maoto, a traditional kampo medicine, has been clinically prescribed for influenza infection and is reported to relieve symptoms and tissue damage
Whereas all mice in the influenza virus inoculation (IVI) group died by 7 dpi, those in the group with a higher dose of MT [IVI + MT(H)] lived for significantly longer (Fig. 1b)
Tam et al.[4] previously examined the changes in lipid mediators in bronchoalveolar lavage during IVI, showing that a lethal infection resulted in an increase in ω-3 fatty acid (FA)-derived lipid mediators at 5 dpi, which is consistent with the trends observed in our data

Summary

Introduction

A traditional kampo medicine, has been clinically prescribed for influenza infection and is reported to relieve symptoms and tissue damage. Analysis of the lung and plasma transcriptome and lipid mediator metabolite profile showed that maoto altered the profile of lipid mediators derived from ω-6 and ω-3 fatty acids to restore a normal state, and significantly up-regulated the expression of macrophage- and T-cell-related genes These results suggest that maoto regulates the host’s inflammatory response by altering the lipid mediator profile and thereby ameliorating the symptoms of influenza. The herbal ingredients in MT directly inhibit influenza viral replication in vitro, and affect inflammatory responses both in vitro and in an in vivo animal model[14,24,25,26,27,28,29,30,31,32,33] While these findings suggest that MT directly inhibits influenza virus infection and regulates the host inflammatory response as a multi-ingredient drug, its detailed mechanism of action has not been clarified

Methods

Results

Conclusion