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

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.

Potency of Tokishakuyakusan in treating preeclampsia: Drug repositioning method by in vitro screening of the Kampo library

“…In addition, they contain various combinations of crude drugs, and it is difficult to determine an appropriate cell experiment concentration. Therefore, concentration was determined based on a previous study [ 18 ]. Furthermore, it is worth trying a variable combination of crude drugs to create a more ideal Kampo drug that increases PlGF.…”

“…Using the techniques employed in previous reports, we purified the drugs by low-speed centrifugation, and then filtered it using a 0.22 μ m filter. The final drug was stored at -30°C before use [ 18 , 19 ].…”

“…concentration was determined based on a previous study [18]. Furthermore, it is worth trying a variable combination of crude drugs to create a more ideal Kampo drug that increases PlGF.…”

A Quinolinone Compound Inhibiting the Oligomerization of Nucleoprotein of Influenza A Virus Prevents the Selection of Escape Mutants

“…After the fifth and ninth passages of the virus in oseltamivir acid and NUD-1, the culture supernatant was harvested. Viral titers were determined using the TCID 50 assay [32], and the sensitivity of the passaged virus to the respective drugs was determined using crystal violet assay as described previously [33]. Isolation of a resistant clone by plaque assay in the presence of 100 µM oseltamivir was performed after the fifth passage.…”

Assessment of the Aromatase Inhibitory Activity of Ma-Huang-Tang (MHT) and Its Active Compounds

“…Traditional alternative medicine has the advantages of subject diversity and multiple active ingredients, and the use of alternative medicines, such as herbal medicines, which are known to contain active medicinal ingredients that have physiological effects on health, has increased [22,23]. Ma-Huang-Tang (MHT), an oriental herbal formula that has been used in Korea for a long time, is composed of six herbs, Ephedrae Herba, Cinnamomi Ramulus, Glycyrrhizae Radix et Rhizoma, Armeniacae Semen, Zingiberis Rhizoma Recens, and Allii Radix, and has traditionally been used in the treatment of sweating, asthma, febrile disease, and inflammatory skin diseases [24][25][26]. MHT also reportedly improves steroid-induced gene expression and ovarian dysfunction [27].…”