Drug-Repositioning Approach for the Discovery of Anti-Influenza Virus Activity of Japanese Herbal (Kampo) Medicines In Vitro: Potent High Activity of Daio-Kanzo-To.

Ken Watanabe

doi:10.1155/2018/6058181

Abstract

Influenza virus infections are a serious public health concern throughout the world. Emergence of viral resistance to the currently approved anti-influenza drugs warrants the development of new antiviral agents. Japanese herbal medicines called Kampo are very commonly used as prescription medication in Japan, and Mao-to is known to be effective against influenza that is caused by oseltamivir-resistant viruses. However, influenza-related death occurs mainly among the elderly, and for patients with hypertension and diabetes, Mao-to may cause these diseases to worsen. Therefore, the exploration of more potent and safe Kampo medicines may be a good strategy for developing new influenza medicines. Here cell-based screening of anti-influenza virus activity for 42 approved Kampo medicines was performed using the drug-repositioning approach. As a result, four Kampo medicines were selected as potent anti-influenza agents against the A/WSN/33 strain. It was found that Daio-kanzo-to [50% inhibitory concentration (IC50) = 10.5 μg/mL; 50% cytotoxic concentration (CC50) = 71.6 μg/mL; selective index = 6.8] is more effective than Mao-to. Daio-kanzo-to and its constituent Japanese Pharmacopoeia (JP) Rhubarb were also effective against H3N2 and H1N1 subtypes of influenza viruses, including oseltamivir-insensitive-2009 pandemic clinical isolates. These data suggest the potential application of Daio-kanzo-to for influenza treatment.

Highlights

Influenza is caused by infection with influenza virus
It has been reported that crude drugs Japanese Valerian and galangal were traditionally used as stomach medicine and sedatives; their constituents valtrate and 1’-acetoxychavicol have anti-influenza virus activity with nuclear export inhibition of the ribonucleoprotein complex [11]
Daio-kanzo-to is used for over-the-counter (OTC) as well as prescription drugs. This is the first report that Daio-kanzo-to, which is not used for communicable diseases, has anti-influenza virus activity

Summary

Introduction

Influenza is caused by infection with influenza virus. The influenza virus binds to sialic acids on the cell surface and is incorporated into the cell via endocytosis. It has been reported that crude drugs Japanese Valerian and galangal were traditionally used as stomach medicine and sedatives; their constituents valtrate and 1’-acetoxychavicol have anti-influenza virus activity with nuclear export inhibition of the ribonucleoprotein complex [11]. It was found that lady’s mantle (which is used for hemostasis and alleviating nausea and vomiting) has anti-influenza activity with virucidal effects [12] These observations show the potential of random screening medicinal plants for the discovery of novel antiviral agents, regardless of the traditional use of the medicinal plants. The anti-influenza virus activity of 42 representative frequently used Kampo medicines was screened using the drug-repositioning approach. Daio-kanzo-to is used for over-the-counter (OTC) as well as prescription drugs This is the first report that Daio-kanzo-to, which is not used for communicable diseases, has anti-influenza virus activity

Materials and Methods

Crystal Violet Assays for Screening and Antiviral Activity

Results

Discussion