Japanese Herbal Medicine (Kampo) Based Antimalarial Drug Development

Abstract

Introduction: Malaria is critical global health issue, especially tropical and subtropical countries. The emergence of resistance to the currently approved drug is a recurring problem thus the urgent development of new medicine with new mechanisms of action is needed. Herbal medicine is still an attractive source of the new antimalarial drug since the isolation of quinine and artemisinin. Kampo is known Japanese traditional medicine that has been used for long periods of time, and the aim of the study is to evaluate the in vitro and in vivo antimalarial activity of Kampo compounds and extracts.

Methods and Material: The antimalarial activity of Kampo library (96 compounds and 120 extracts), which were provided by University of Toyama (Japan) were evaluated using in vitro antimalarial assay against two laboratory strain of Plasmodium falciparum in the erythrocytic stage. After the drug treatment, the red blood cells were stained with SYBR Green to detect the parasite. In addition to this, the cytotoxicity was also examined. Moreover, active Kampo crude drug extract and formula which contains the crude extract were further examined against P. yoelii in mouse model. In vivo parasite growth suppression effect of crude drug extract and formula were evaluated in mice inoculated with P. yoelii (1x10⁴ parasite/mouse).

Result: Our results of first screening yielded a total of 12 compounds possessing antimalarial activity against chloroquine/mefloquine sensitive 3D7A strain, of which 3 were toxic. Among them, one compound (coptisine chloride) showed high activity (IC₅₀ 1.1 μM) and its SI was 37.8. Twenty-seven extracts out of 120 extracts showed antimalarial effect. Among them, one crude drug extract (Coptis Rhizome) showed high activity (IC₅₀ 2.5 μg/mL) and its SI was more than 200. In addition, both the formula (Orengedokuto) and crude drug extract (Coptis Rhizome) showed a suppression of parasitemia even in a preliminary experiment with mouse model.

Conclusion: High antimalarial activity was observed from some Kampo compounds and crude drug extracts. These results lead us to examine Kampo formula as an antimalarial drug candidate. This study will be an input for the advanced development of the antimalarial drug from Japanese herbal (Kampo) medicine.