Antidiarrheal efficacy and cellular mechanisms of a Thai herbal remedy.
Screening of herbal remedies for Cl(-) channel inhibition identified Krisanaklan, a herbal extract used in Thailand for treatment of diarrhea, as an effective antidiarrheal in mouse models of secretory diarrheas with inhibition activity against three Cl(-) channel targets. Krisanaklan fully inhibite...
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ftdoajarticles:oai:doaj.org/article:efedb2bcf7294a3b92c84603710e371e 2023-05-15T15:09:07+02:00 Antidiarrheal efficacy and cellular mechanisms of a Thai herbal remedy. Lukmanee Tradtrantip Eun-A Ko Alan S Verkman 2014-02-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0002674 https://doaj.org/article/efedb2bcf7294a3b92c84603710e371e EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3923670?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002674 https://doaj.org/article/efedb2bcf7294a3b92c84603710e371e PLoS Neglected Tropical Diseases, Vol 8, Iss 2, p e2674 (2014) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2014 ftdoajarticles https://doi.org/10.1371/journal.pntd.0002674 2022-12-30T21:58:07Z Screening of herbal remedies for Cl(-) channel inhibition identified Krisanaklan, a herbal extract used in Thailand for treatment of diarrhea, as an effective antidiarrheal in mouse models of secretory diarrheas with inhibition activity against three Cl(-) channel targets. Krisanaklan fully inhibited cholera toxin-induced intestinal fluid secretion in a closed-loop mouse model with ∼50% inhibition at a 1 ∶ 50 dilution of the extract. Orally administered Krisanaklan (5 µL/g) prevented rotavirus-induced diarrhea in neonatal mice. Short-circuit current measurements showed full inhibition of cAMP and Ca(2+) agonist-induced Cl(-) conductance in human colonic epithelial T84 cells, with ∼ 50% inhibition at a 1 ∶ 5,000 dilution of the extract. Krisanaklan also strongly inhibited intestinal smooth muscle contraction in an ex vivo preparation. Together with measurements using specific inhibitors, we conclude that the antidiarrheal actions of Krisanaklan include inhibition of luminal CFTR and Ca(2+)-activated Cl(-) channels in enterocytes. HPLC fractionation indicated that the three Cl(-) inhibition actions of Krisanaklan are produced by different components in the herbal extract. Testing of individual herbs comprising Krisanaklan indicated that agarwood and clove extracts as primarily responsible for Cl(-) channel inhibition. The low cost, broad antidiarrheal efficacy, and defined cellular mechanisms of Krisanaklan suggests its potential application for antisecretory therapy of cholera and other enterotoxin-mediated secretory diarrheas in developing countries. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 8 2 e2674 |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Lukmanee Tradtrantip Eun-A Ko Alan S Verkman Antidiarrheal efficacy and cellular mechanisms of a Thai herbal remedy. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Screening of herbal remedies for Cl(-) channel inhibition identified Krisanaklan, a herbal extract used in Thailand for treatment of diarrhea, as an effective antidiarrheal in mouse models of secretory diarrheas with inhibition activity against three Cl(-) channel targets. Krisanaklan fully inhibited cholera toxin-induced intestinal fluid secretion in a closed-loop mouse model with ∼50% inhibition at a 1 ∶ 50 dilution of the extract. Orally administered Krisanaklan (5 µL/g) prevented rotavirus-induced diarrhea in neonatal mice. Short-circuit current measurements showed full inhibition of cAMP and Ca(2+) agonist-induced Cl(-) conductance in human colonic epithelial T84 cells, with ∼ 50% inhibition at a 1 ∶ 5,000 dilution of the extract. Krisanaklan also strongly inhibited intestinal smooth muscle contraction in an ex vivo preparation. Together with measurements using specific inhibitors, we conclude that the antidiarrheal actions of Krisanaklan include inhibition of luminal CFTR and Ca(2+)-activated Cl(-) channels in enterocytes. HPLC fractionation indicated that the three Cl(-) inhibition actions of Krisanaklan are produced by different components in the herbal extract. Testing of individual herbs comprising Krisanaklan indicated that agarwood and clove extracts as primarily responsible for Cl(-) channel inhibition. The low cost, broad antidiarrheal efficacy, and defined cellular mechanisms of Krisanaklan suggests its potential application for antisecretory therapy of cholera and other enterotoxin-mediated secretory diarrheas in developing countries. |
format |
Article in Journal/Newspaper |
author |
Lukmanee Tradtrantip Eun-A Ko Alan S Verkman |
author_facet |
Lukmanee Tradtrantip Eun-A Ko Alan S Verkman |
author_sort |
Lukmanee Tradtrantip |
title |
Antidiarrheal efficacy and cellular mechanisms of a Thai herbal remedy. |
title_short |
Antidiarrheal efficacy and cellular mechanisms of a Thai herbal remedy. |
title_full |
Antidiarrheal efficacy and cellular mechanisms of a Thai herbal remedy. |
title_fullStr |
Antidiarrheal efficacy and cellular mechanisms of a Thai herbal remedy. |
title_full_unstemmed |
Antidiarrheal efficacy and cellular mechanisms of a Thai herbal remedy. |
title_sort |
antidiarrheal efficacy and cellular mechanisms of a thai herbal remedy. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2014 |
url |
https://doi.org/10.1371/journal.pntd.0002674 https://doaj.org/article/efedb2bcf7294a3b92c84603710e371e |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 8, Iss 2, p e2674 (2014) |
op_relation |
http://europepmc.org/articles/PMC3923670?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002674 https://doaj.org/article/efedb2bcf7294a3b92c84603710e371e |
op_doi |
https://doi.org/10.1371/journal.pntd.0002674 |
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PLoS Neglected Tropical Diseases |
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8 |
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2 |
container_start_page |
e2674 |
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