TY - JOUR
T1 - Anti-malarial activity of traditional Kampo medicine Coptis rhizome extract and its major active compounds
AU - Teklemichael, Awet Alem
AU - Teklemichael, Awet Alem
AU - Teklemichael, Awet Alem
AU - Mizukami, Shusaku
AU - Mizukami, Shusaku
AU - Toume, Kazufumi
AU - Mosaddeque, Farhana
AU - Mosaddeque, Farhana
AU - Kamel, Mohamed Gomaa
AU - Kaneko, Osamu
AU - Kaneko, Osamu
AU - Kaneko, Osamu
AU - Komatsu, Katsuko
AU - Karbwang, Juntra
AU - Karbwang, Juntra
AU - Huy, Nguyen Tien
AU - Hirayama, Kenji
N1 - Publisher Copyright:
© 2020 The Author(s).
PY - 2020/6/8
Y1 - 2020/6/8
N2 - Background: Herbal medicine has been a rich source of new drugs exemplified by quinine and artemisinin. In this study, a variety of Japanese traditional herbal medicine ('Kampo') were examined for their potential anti-malarial activities. Methods: A comprehensive screening methods were designed to identify novel anti-malarial drugs from a library of Kampo herbal extracts (n = 120) and related compounds (n = 96). The anti-malarial activity was initially evaluated in vitro against chloroquine/mefloquine-sensitive (3D7) and-resistant (Dd2) strains of Plasmodium falciparum. The cytotoxicity was also evaluated using primary adult mouse brain cells. After being selected through the first in vitro assay, positive extracts and compounds were examined for possible in vivo anti-malarial activity. Results: Out of 120 herbal extracts, Coptis rhizome showed the highest anti-malarial activity (IC50 1.9 μg/mL of 3D7 and 4.85 μg/mL of Dd2) with a high selectivity index (SI) > 263 (3D7) and > 103 (Dd2). Three major chlorinated compounds (coptisine, berberine, and palmatine) related to Coptis rhizome also showed anti-malarial activities with IC50 1.1, 2.6, and 6.0 μM (against 3D7) and 3.1, 6.3, and 11.8 μM (against Dd2), respectively. Among them, coptisine chloride exhibited the highest anti-malarial activity (IC50 1.1 μM against 3D7 and 3.1 μM against Dd2) with SI of 37.8 and 13.2, respectively. Finally, the herbal extract of Coptis rhizome and its major active compound coptisine chloride exhibited significant anti-malarial activity in mice infected with Plasmodium yoelii 17X strain with respect to its activity on parasite suppression consistently from day 3 to day 7 post-challenge. The effect ranged from 50.38 to 72.13% (P < 0.05) for Coptis rhizome and from 81 to 89% (P < 0.01) for coptisine chloride. Conclusion: Coptis rhizome and its major active compound coptisine chloride showed promising anti-malarial activity against chloroquine-sensitive (3D7) and -resistant (Dd2) strains in vitro as well as in vivo mouse malaria model. Thus, Kampo herbal medicine is a potential natural resource for novel anti-malarial agents.
AB - Background: Herbal medicine has been a rich source of new drugs exemplified by quinine and artemisinin. In this study, a variety of Japanese traditional herbal medicine ('Kampo') were examined for their potential anti-malarial activities. Methods: A comprehensive screening methods were designed to identify novel anti-malarial drugs from a library of Kampo herbal extracts (n = 120) and related compounds (n = 96). The anti-malarial activity was initially evaluated in vitro against chloroquine/mefloquine-sensitive (3D7) and-resistant (Dd2) strains of Plasmodium falciparum. The cytotoxicity was also evaluated using primary adult mouse brain cells. After being selected through the first in vitro assay, positive extracts and compounds were examined for possible in vivo anti-malarial activity. Results: Out of 120 herbal extracts, Coptis rhizome showed the highest anti-malarial activity (IC50 1.9 μg/mL of 3D7 and 4.85 μg/mL of Dd2) with a high selectivity index (SI) > 263 (3D7) and > 103 (Dd2). Three major chlorinated compounds (coptisine, berberine, and palmatine) related to Coptis rhizome also showed anti-malarial activities with IC50 1.1, 2.6, and 6.0 μM (against 3D7) and 3.1, 6.3, and 11.8 μM (against Dd2), respectively. Among them, coptisine chloride exhibited the highest anti-malarial activity (IC50 1.1 μM against 3D7 and 3.1 μM against Dd2) with SI of 37.8 and 13.2, respectively. Finally, the herbal extract of Coptis rhizome and its major active compound coptisine chloride exhibited significant anti-malarial activity in mice infected with Plasmodium yoelii 17X strain with respect to its activity on parasite suppression consistently from day 3 to day 7 post-challenge. The effect ranged from 50.38 to 72.13% (P < 0.05) for Coptis rhizome and from 81 to 89% (P < 0.01) for coptisine chloride. Conclusion: Coptis rhizome and its major active compound coptisine chloride showed promising anti-malarial activity against chloroquine-sensitive (3D7) and -resistant (Dd2) strains in vitro as well as in vivo mouse malaria model. Thus, Kampo herbal medicine is a potential natural resource for novel anti-malarial agents.
KW - Antimalarial
KW - Herbal medicine
KW - Kampo
UR - http://www.scopus.com/inward/record.url?scp=85086298883&partnerID=8YFLogxK
U2 - 10.1186/s12936-020-03273-x
DO - 10.1186/s12936-020-03273-x
M3 - 学術論文
C2 - 32513250
AN - SCOPUS:85086298883
SN - 1475-2875
VL - 19
JO - Malaria Journal
JF - Malaria Journal
IS - 1
M1 - 204
ER -