Mechanism of Action of the Anti-Influenza Virus Active Kampo (Traditional Japanese Herbal) Medicine, Hochuekkito

Abstract

When the Kampo medicine, Hochuekkito (Hochu), was administered to normal mice for 2 weeks, influenza virus titer was reduced. The mechanism of action of Hochu was examined using the plaque assay method. It was suggested that Hochu may either obstruct the first stage of the infection process (adsorption and entry) or may directly target viral particles. Using the plaque assay method, these 2 modes of action could not be differentiated. Virus RNA in the infected cell was verified by quantitative real-time polymerase chain reaction. An equal inhibition effect was obtained when Hochu was preprocessed for normal cells and when they were made to act simultaneously with virus adsorption. The viral load at the cell surface following UV irradiation was higher in the Hochu-administered group as compared with that of the control. Moreover, the affinity of Hochu for the influenza virus was hundred times higher than its affinity for the host cell. The effect of entry obstruction by Hochu was observed via image analysis, where the amount of virus nucleocapsid protein (NP) invading the cell was visualized with FITC-labeled NP antibody. Hochu does not seem to have an effect on nucleic acid synthesis, viral release from infected cells, and on the subsequent second round of infection. In conclusion, Hochu binds to viral particles and forms complexes that can obstruct the entry of influenza virus into cells.

Basic pharmacological mechanisms and clinical evidence of the efficacy of hochuekkito against infectious diseases and its potential for use against COVID‐19

“…HET has an effect on innate immunity as shown by increases in NK activity and cytokines. In infection models of bacterial [23,26–30] and viral infection [31–36], HET also increased cytokines. The effects on various cytokines are recognized for the whole body, notably the lung and alveoli (Fig.…”

“…In animal models of immune deficiency by age [20], steroids [21], cyclophosphamide [22], mitomycin C [23], and restraint stress [24,25], HET improved reduced immune function by both innate and acquired immunity. Related to these immuno‐stimulatory effects, HET exhibited a preventive effect from infection by Salmonella enteritidis [26], Listeria monocytogenes [27,28], Helicobacter pylori [29], methicillin‐resistant Staphylococcus aureus (MRSA) [30], influenza virus [31–35], cytomegalovirus [36], and Plasmodium chabaudi [37]. HET also exhibited a protective effect on cancer caused by inoculation of cancer cells [38,39] or carcinogenic substances [40–42].…”

Which East Asian herbal medicines can decrease viral infections?

“…In Japan several Kampo prescriptions like Maoto, Kakkonto (Kurokawa et al 1996;Okabayashi et al 2014), Shahakusan (Hokari et al 2012), Shoseiryuto Yamada 1994, 1998;Nagai et al 1996;Yamada and Nagai 1998), Daiokanzoto (Watanabe 2018) and Hochuekkito (Dan et al 2018) (Table 1) have been investigated for their effect against influenza virus infection.…”

Inhibitory effect of traditional herbal (kampo) medicines on the replication of human parainfluenza virus type 2 <i>in vitro </i>

“…Maoto has clinical and virological efficacy for influenza virus by inhibiting uncoating of influenza virus A (11). Hochuekkito also has protective effects against influenza virus, and it stimulates the upper respiratory mucosal immune system (12). However, there are no reports on the effect of traditional herbal medicines on human parainfluenza viruses.…”