Alternative Title漢方生薬オウレンとその主要活性化合物の抗マラリア活性
Degree grantor/typeNagasaki University (長崎大学)
Note (General)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.
長崎大学学位論文 学位記番号:博(医歯薬)甲第1358号 学位授与年月日:令和3年9月17日
Author: Awet Alem Teklemichael, Shusaku Mizukami, Kazufumi Toume, Farhana Mosaddeque, Mohamed Gomaa Kamel, Osamu Kaneko, Katsuko Komatsu, Juntra Karbwang, Nguyen Tien Huy & Kenji Hirayama
Citation: Malaria Journal, 19, art. no. 204; 2020
identifier:Nagasaki University (長崎大学), 博士(医学) (2021-09-17)
http://hdl.handle.net/10069/00040841
DOIinfo:doi/10.1186/s12936-020-03273-x
Collection (particular)国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
Date Accepted (W3CDTF)2021-11-08T14:10:24+09:00
Data Provider (Database)国立国会図書館 : 国立国会図書館デジタルコレクション