Anti-malarial activity of traditional Kampo medicine Coptis rhizome extract and its major active compounds

• Material Type: 博士論文
• Title: Anti-malarial activity of traditional Kampo medicine Coptis rhizome extract and its major active compounds
• Author/Editor: Teklemichael, Awet Alem
• Author Heading: Teklemichael, Awet Alem
• Publication, Distribution, etc.: BioMed Central Ltd
• Publication Date: 2020-06-08
• Publication Date (W3CDTF): 2020-06-08
• 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
• Periodical title: Malaria Journal
• No. or year of volume/issue: 19
• Volume: 19
• Pages: art. no. 204-
• ISSN (Periodical Title): ISSN : 1475-2875
• Degree grantor/type: Nagasaki University (長崎大学)
• Date Granted: 2021-09-17
• Dissertation Number: 甲医歯薬第1358号
• Degree Type: 博士(医学)
• Text Language Code: eng
• Subject Heading: Herbal medicine; Kampo; Antimalarial
• Target Audience: 一般
• 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)
• Source: fulltext; https://nagasaki-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=26752&item_no=1&attribute_id=70&file_no=1
• Access Restrictions: インターネット公開
• Rights (production): © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat iveco mmons .org/licen ses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/publi cdoma in/ zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
• Related Material: http://hdl.handle.net/10069/00040841
• Related Material (DOI): 10.1186/s12936-020-03273-x
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 長崎大学 : 長崎大学学術研究成果リポジトリ