Anti-Trypanosoma cruzi activity of Coptis rhizome extract and its constituents.

Chagas disease Coptis rhizome extract Coptisine chloride Isoquinoline alkaloid Trypanosoma cruzi

Journal

Tropical medicine and health
ISSN: 1348-8945
Titre abrégé: Trop Med Health
Pays: Japan
ID NLM: 101215093

Informations de publication

Date de publication:
01 Mar 2023
Historique:
received: 30 12 2022
accepted: 09 02 2023
entrez: 1 3 2023
pubmed: 2 3 2023
medline: 2 3 2023
Statut: epublish

Résumé

Current therapeutic agents, including nifurtimox and benznidazole, are not sufficiently effective in the chronic phase of Trypanosoma cruzi infection and are accompanied by various side effects. In this study, 120 kinds of extracts from medicinal herbs used for Kampo formulations and 94 kinds of compounds isolated from medicinal herbs for Kampo formulations were screened for anti-T. cruzi activity in vitro and in vivo. As an experimental method, a recombinant protozoan cloned strain expressing luciferase, namely Luc2-Tulahuen, was used in the experiments. The in vitro anti-T. cruzi activity on epimastigote, trypomastigote, and amastigote forms was assessed by measuring luminescence intensity after treatment with the Kampo extracts or compounds. In addition, the cytotoxicity of compounds was tested using mouse and human feeder cell lines. The in vivo anti-T. cruzi activity was measured by a murine acute infection model using intraperitoneal injection of trypomastigotes followed by live bioluminescence imaging. As a result, three protoberberine-type alkaloids, namely coptisine chloride, dehydrocorydaline nitrate, and palmatine chloride, showed strong anti-T. cruzi activities with low cytotoxicity. The IC For these reasons, coptisine chloride is a hit compound that can be a potential candidate for anti-Chagas disease drugs. In addition, it was expected that there would be room for further improvement by modifying the side chains of the basic skeleton.

Sections du résumé

BACKGROUND BACKGROUND
Current therapeutic agents, including nifurtimox and benznidazole, are not sufficiently effective in the chronic phase of Trypanosoma cruzi infection and are accompanied by various side effects. In this study, 120 kinds of extracts from medicinal herbs used for Kampo formulations and 94 kinds of compounds isolated from medicinal herbs for Kampo formulations were screened for anti-T. cruzi activity in vitro and in vivo.
METHODS METHODS
As an experimental method, a recombinant protozoan cloned strain expressing luciferase, namely Luc2-Tulahuen, was used in the experiments. The in vitro anti-T. cruzi activity on epimastigote, trypomastigote, and amastigote forms was assessed by measuring luminescence intensity after treatment with the Kampo extracts or compounds. In addition, the cytotoxicity of compounds was tested using mouse and human feeder cell lines. The in vivo anti-T. cruzi activity was measured by a murine acute infection model using intraperitoneal injection of trypomastigotes followed by live bioluminescence imaging.
RESULTS RESULTS
As a result, three protoberberine-type alkaloids, namely coptisine chloride, dehydrocorydaline nitrate, and palmatine chloride, showed strong anti-T. cruzi activities with low cytotoxicity. The IC
CONCLUSIONS CONCLUSIONS
For these reasons, coptisine chloride is a hit compound that can be a potential candidate for anti-Chagas disease drugs. In addition, it was expected that there would be room for further improvement by modifying the side chains of the basic skeleton.

Identifiants

DOI: 10.1186/s41182-023-00502-2 PMID: 36859380 PMC: PMC9976467
pubmed: 36859380
doi: 10.1186/s41182-023-00502-2
pii: 10.1186/s41182-023-00502-2
pmc: PMC9976467
doi:

Types de publication

Journal Article

Langues

eng

Pagination

12

Subventions

Organisme : Nagasaki University
ID : 29-Ippan-17
Organisme : Nagasaki University
ID : 2018-Ippan-21
Organisme : Institute of Agriculture and Natural Resources
ID : Ippan Kenkyu I

Informations de copyright

© 2023. The Author(s).

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Auteurs

Yuki Tayama (Y)

Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.

Shusaku Mizukami (S)

Department of Immune Regulation, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan.
School of Tropical Medicines and Global Health, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
The Joint Usage/Research Center On Tropical Disease, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, 852-8523, Japan.
ORCID: 0000-0002-7722-4884

Kazufumi Toume (K)

Section of Pharmacognosy, Institute of Natural Medicine, University of Toyama, Toyama, Japan.
ORCID: 0000-0002-3315-145X

Katsuko Komatsu (K)

Section of Pharmacognosy, Institute of Natural Medicine, University of Toyama, Toyama, Japan.
ORCID: 0000-0002-0833-7199

Tetsuo Yanagi (T)

NEKKEN Bio-Resource Center (NBRC), Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan.
The Joint Usage/Research Center On Tropical Disease, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, 852-8523, Japan.

Takeshi Nara (T)

Faculty of Pharmacy, Iryo Sosei University, Iwaki, Fukushima, Japan.

Paul Tieu (P)

Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.
Online Research Club, Nagasaki, Japan.
ORCID: 0000-0003-4907-664X

Nguyen Tien Huy (NT)

Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
School of Tropical Medicines and Global Health, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
Online Research Club, Nagasaki, Japan.
ORCID: 0000-0002-9543-9440

Shinjiro Hamano (S)

Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
Department of Parasitology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan.
The Joint Usage/Research Center On Tropical Disease, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, 852-8523, Japan.
ORCID: 0000-0003-3881-8337

Kenji Hirayama (K)

Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan. hiraken@nagasaki-u.ac.jp.
Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan. hiraken@nagasaki-u.ac.jp.
School of Tropical Medicines and Global Health, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan. hiraken@nagasaki-u.ac.jp.
The Joint Usage/Research Center On Tropical Disease, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, 852-8523, Japan. hiraken@nagasaki-u.ac.jp.
ORCID: 0000-0001-9467-1777

Classifications MeSH