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Inchinkoto, the Traditional Japanese Kampo Medicine, Enhances Intestinal Epithelial Barrier Function In Vitro
Inchinkoto (ICKT), a traditional herbal medicine that is often used as a hepatoprotective drug in Japan, has pharmacological properties that include antioxidant, anti-inflammatory, and choleretic actions. Genipin is a metabolite of geniposide and the most abundant ingredient of ICKT; furthermore, it...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536930/ https://www.ncbi.nlm.nih.gov/pubmed/36212959 http://dx.doi.org/10.1155/2022/4139812 |
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author | Nakao, Ayaka Hu, Ailing Yamaguchi, Takuji Tabuchi, Masahiro Ikarashi, Yasushi Kobayashi, Hiroyuki |
author_facet | Nakao, Ayaka Hu, Ailing Yamaguchi, Takuji Tabuchi, Masahiro Ikarashi, Yasushi Kobayashi, Hiroyuki |
author_sort | Nakao, Ayaka |
collection | PubMed |
description | Inchinkoto (ICKT), a traditional herbal medicine that is often used as a hepatoprotective drug in Japan, has pharmacological properties that include antioxidant, anti-inflammatory, and choleretic actions. Genipin is a metabolite of geniposide and the most abundant ingredient of ICKT; furthermore, it is considered to be the active substance responsible for its pharmacological properties in the liver. Drugs with such pharmacological characteristics are expected to prevent intestinal barrier dysfunction, which causes inflammatory bowel diseases (IBDs). However, no studies have investigated the effects of ICKT on the intestinal epithelial barrier. Therefore, we investigated the activity of ICKT in intestinal tight junctions by using cultured Caco-2 cell monolayers. The action of the compound on tight junctions was examined by measuring transepithelial electrical resistance (TEER) and sodium fluorescein (Na-F) permeability in the presence or absence of lipopolysaccharide (LPS). Moreover, the expression of the tight junction protein claudin-1 was assessed by using immunofluorescent staining. ICKT and genipin increased TEER and decreased Na-F permeability, which was suggestive of enhanced intestinal epithelial barrier function. Moreover, they prevented the LPS-induced destruction of the barrier, i.e., a decrease in TEER and an increase in Na-F permeability. Immunofluorescence staining revealed a high claudin-1 expression level on the cell surface, whereas exposure to LPS downregulated claudin-1. In turn, ICKT and genipin prevented the LPS-mediated reduction of claudin-1. These results suggest that ICKT enhances intestinal epithelial barrier function by upregulating claudin-1. Furthermore, genipin contributed to these effects. ICKT may be a promising medicine for the prevention and treatment of diseases associated with intestinal barrier disruption, such as IBD, obesity, and metabolic disorders. |
format | Online Article Text |
id | pubmed-9536930 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-95369302022-10-07 Inchinkoto, the Traditional Japanese Kampo Medicine, Enhances Intestinal Epithelial Barrier Function In Vitro Nakao, Ayaka Hu, Ailing Yamaguchi, Takuji Tabuchi, Masahiro Ikarashi, Yasushi Kobayashi, Hiroyuki Evid Based Complement Alternat Med Research Article Inchinkoto (ICKT), a traditional herbal medicine that is often used as a hepatoprotective drug in Japan, has pharmacological properties that include antioxidant, anti-inflammatory, and choleretic actions. Genipin is a metabolite of geniposide and the most abundant ingredient of ICKT; furthermore, it is considered to be the active substance responsible for its pharmacological properties in the liver. Drugs with such pharmacological characteristics are expected to prevent intestinal barrier dysfunction, which causes inflammatory bowel diseases (IBDs). However, no studies have investigated the effects of ICKT on the intestinal epithelial barrier. Therefore, we investigated the activity of ICKT in intestinal tight junctions by using cultured Caco-2 cell monolayers. The action of the compound on tight junctions was examined by measuring transepithelial electrical resistance (TEER) and sodium fluorescein (Na-F) permeability in the presence or absence of lipopolysaccharide (LPS). Moreover, the expression of the tight junction protein claudin-1 was assessed by using immunofluorescent staining. ICKT and genipin increased TEER and decreased Na-F permeability, which was suggestive of enhanced intestinal epithelial barrier function. Moreover, they prevented the LPS-induced destruction of the barrier, i.e., a decrease in TEER and an increase in Na-F permeability. Immunofluorescence staining revealed a high claudin-1 expression level on the cell surface, whereas exposure to LPS downregulated claudin-1. In turn, ICKT and genipin prevented the LPS-mediated reduction of claudin-1. These results suggest that ICKT enhances intestinal epithelial barrier function by upregulating claudin-1. Furthermore, genipin contributed to these effects. ICKT may be a promising medicine for the prevention and treatment of diseases associated with intestinal barrier disruption, such as IBD, obesity, and metabolic disorders. Hindawi 2022-09-29 /pmc/articles/PMC9536930/ /pubmed/36212959 http://dx.doi.org/10.1155/2022/4139812 Text en Copyright © 2022 Ayaka Nakao et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Nakao, Ayaka Hu, Ailing Yamaguchi, Takuji Tabuchi, Masahiro Ikarashi, Yasushi Kobayashi, Hiroyuki Inchinkoto, the Traditional Japanese Kampo Medicine, Enhances Intestinal Epithelial Barrier Function In Vitro |
title | Inchinkoto, the Traditional Japanese Kampo Medicine, Enhances Intestinal Epithelial Barrier Function In Vitro |
title_full | Inchinkoto, the Traditional Japanese Kampo Medicine, Enhances Intestinal Epithelial Barrier Function In Vitro |
title_fullStr | Inchinkoto, the Traditional Japanese Kampo Medicine, Enhances Intestinal Epithelial Barrier Function In Vitro |
title_full_unstemmed | Inchinkoto, the Traditional Japanese Kampo Medicine, Enhances Intestinal Epithelial Barrier Function In Vitro |
title_short | Inchinkoto, the Traditional Japanese Kampo Medicine, Enhances Intestinal Epithelial Barrier Function In Vitro |
title_sort | inchinkoto, the traditional japanese kampo medicine, enhances intestinal epithelial barrier function in vitro |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536930/ https://www.ncbi.nlm.nih.gov/pubmed/36212959 http://dx.doi.org/10.1155/2022/4139812 |
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