Hochu-ekki-to inhibits rhinovirus infection in human tracheal epithelial cells

Background and purpose: A traditional Japanese herbal medicine, hochu-ekki- to, has been used for the symptomatic treatment of the common cold and to reduce the frequency of colds in patients with chronic obstructive pulmonary disease. However, the inhibitory effects of hochu-ekki- to on infection by rhinovirus ( RV), the major cause of common colds, have not been studied. Experimental approach: Human tracheal epithelial cells in culture were infected with a major group rhinovirus- RV14. Virus output and viral RNA were measured along with interleukin ( IL)-1 beta, IL-6, IL-8 and tumor necrosis factor ( TNF)-alpha), mRNA for intercellular adhesion molecule ( ICAM)-1 and acidic endosomes in cells. Key results: RV14 infection increased virus titers, the content of cytokines in supernatants and RV14 RNA in the cells. Hochu-ekki-to decreased virus output, RV14 RNA in the cells, susceptibility to RV infection and supernatant cytokine concentrations after RV14 infection. Hochu-ekki-to reduced mRNA for ICAM- 1, the receptor for RV14, the concentration of the soluble form of ICAM- 1 and the number and fluorescence intensity of acidic endosomes in the cells, from which RV RNA enters into the cytoplasm, at RV14 infection. Glycyrrhizin, one of the chemical constituents of hochu-ekki-to, reduced supernatant virus titers dose-dependently. Conclusion and implications: Hochu-ekki-to inhibited RV14 infection by decreasing ICAM- 1 and by blocking entry of viral RNA into the cytoplasm from the endosomes, in airway epithelial cells. Glycyrrhizin may be partly responsible for inhibition of RV infection by hochu-ekki-to. Hochu-ekki-to could modulate airway inflammation by reducing production of cytokines in RV infections.