Cargando…

Carnosol Maintains Intestinal Barrier Function and Mucosal Immune Homeostasis in DSS-Induced Colitis

Ulcerative colitis (UC) is a chronic inflammatory disease, characterized by recurrent flares of mucosal inflammation, which is limited in the colon and rectum. Compromised epithelial barrier functions have been indicated in the initiation of UC. Carnosol (CA), a natural active ortho-diphenol diterpe...

Descripción completa

Detalles Bibliográficos
Autores principales: Xu, Xiang, Zhang, Gao, Peng, Kun, Gao, Yanping, Wang, Jinxia, Gao, Caiping, He, Chong, Lu, Fang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9172907/
https://www.ncbi.nlm.nih.gov/pubmed/35685885
http://dx.doi.org/10.3389/fnut.2022.894307
_version_ 1784721930997202944
author Xu, Xiang
Zhang, Gao
Peng, Kun
Gao, Yanping
Wang, Jinxia
Gao, Caiping
He, Chong
Lu, Fang
author_facet Xu, Xiang
Zhang, Gao
Peng, Kun
Gao, Yanping
Wang, Jinxia
Gao, Caiping
He, Chong
Lu, Fang
author_sort Xu, Xiang
collection PubMed
description Ulcerative colitis (UC) is a chronic inflammatory disease, characterized by recurrent flares of mucosal inflammation, which is limited in the colon and rectum. Compromised epithelial barrier functions have been indicated in the initiation of UC. Carnosol (CA), a natural active ortho-diphenol diterpene compound, is one of the active ingredients in plants such as rosemary and sage. The anti-inflammatory and anti-oxidative effects of CA have been reported in several animal models, but its effect on mucosal inflammation remains elusive. We established a mouse experimental colitis model characterized by epithelial barrier destruction using dextran sulfate sodium (DSS). CA was intraperitoneally administrated. Flow cytometry was performed to determine phenotypes of intraepithelial lymphocytes and lamina propria cells. qRT-PCR was used for gene expression. ER stress in the colon was determined by immunofluorescence staining and qRT-PCR. Thapsigargin was used to induce ER stress in HCT-116 cells in vitro. We found CA significantly alleviated DSS-induced colitis in mice marked by relieved clinical symptoms and colonic pathological damage. Inflammatory cell infiltration and cytokine expression in the colon were suppressed by CA during colitis. Furthermore, CA restored epithelial barrier functions and intestinal intraepithelial lymphocyte (IEL) homeostasis in mice with DSS insults. Mechanistically, we induced endoplasmic reticulum (ER) stress in HCT-116 cells (an intestinal epithelial cell line) with thapsigargin, and CA reversed this effect. In addition, we collected inflamed mucosal biopsies from 23 patients with UC, and cultured overnight with or without CA, showing CA significantly reduced expression of ER stress signaling molecule and pro-inflammatory agents. Our data demonstrate that CA acts as an effective drug for experimental colitis and maintains proper epithelial barrier functions via suppressing epithelial ER stress, providing new evidence that CA might be a promising therapeutic candidate for UC.
format Online
Article
Text
id pubmed-9172907
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-91729072022-06-08 Carnosol Maintains Intestinal Barrier Function and Mucosal Immune Homeostasis in DSS-Induced Colitis Xu, Xiang Zhang, Gao Peng, Kun Gao, Yanping Wang, Jinxia Gao, Caiping He, Chong Lu, Fang Front Nutr Nutrition Ulcerative colitis (UC) is a chronic inflammatory disease, characterized by recurrent flares of mucosal inflammation, which is limited in the colon and rectum. Compromised epithelial barrier functions have been indicated in the initiation of UC. Carnosol (CA), a natural active ortho-diphenol diterpene compound, is one of the active ingredients in plants such as rosemary and sage. The anti-inflammatory and anti-oxidative effects of CA have been reported in several animal models, but its effect on mucosal inflammation remains elusive. We established a mouse experimental colitis model characterized by epithelial barrier destruction using dextran sulfate sodium (DSS). CA was intraperitoneally administrated. Flow cytometry was performed to determine phenotypes of intraepithelial lymphocytes and lamina propria cells. qRT-PCR was used for gene expression. ER stress in the colon was determined by immunofluorescence staining and qRT-PCR. Thapsigargin was used to induce ER stress in HCT-116 cells in vitro. We found CA significantly alleviated DSS-induced colitis in mice marked by relieved clinical symptoms and colonic pathological damage. Inflammatory cell infiltration and cytokine expression in the colon were suppressed by CA during colitis. Furthermore, CA restored epithelial barrier functions and intestinal intraepithelial lymphocyte (IEL) homeostasis in mice with DSS insults. Mechanistically, we induced endoplasmic reticulum (ER) stress in HCT-116 cells (an intestinal epithelial cell line) with thapsigargin, and CA reversed this effect. In addition, we collected inflamed mucosal biopsies from 23 patients with UC, and cultured overnight with or without CA, showing CA significantly reduced expression of ER stress signaling molecule and pro-inflammatory agents. Our data demonstrate that CA acts as an effective drug for experimental colitis and maintains proper epithelial barrier functions via suppressing epithelial ER stress, providing new evidence that CA might be a promising therapeutic candidate for UC. Frontiers Media S.A. 2022-05-24 /pmc/articles/PMC9172907/ /pubmed/35685885 http://dx.doi.org/10.3389/fnut.2022.894307 Text en Copyright © 2022 Xu, Zhang, Peng, Gao, Wang, Gao, He and Lu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Nutrition
Xu, Xiang
Zhang, Gao
Peng, Kun
Gao, Yanping
Wang, Jinxia
Gao, Caiping
He, Chong
Lu, Fang
Carnosol Maintains Intestinal Barrier Function and Mucosal Immune Homeostasis in DSS-Induced Colitis
title Carnosol Maintains Intestinal Barrier Function and Mucosal Immune Homeostasis in DSS-Induced Colitis
title_full Carnosol Maintains Intestinal Barrier Function and Mucosal Immune Homeostasis in DSS-Induced Colitis
title_fullStr Carnosol Maintains Intestinal Barrier Function and Mucosal Immune Homeostasis in DSS-Induced Colitis
title_full_unstemmed Carnosol Maintains Intestinal Barrier Function and Mucosal Immune Homeostasis in DSS-Induced Colitis
title_short Carnosol Maintains Intestinal Barrier Function and Mucosal Immune Homeostasis in DSS-Induced Colitis
title_sort carnosol maintains intestinal barrier function and mucosal immune homeostasis in dss-induced colitis
topic Nutrition
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9172907/
https://www.ncbi.nlm.nih.gov/pubmed/35685885
http://dx.doi.org/10.3389/fnut.2022.894307
work_keys_str_mv AT xuxiang carnosolmaintainsintestinalbarrierfunctionandmucosalimmunehomeostasisindssinducedcolitis
AT zhanggao carnosolmaintainsintestinalbarrierfunctionandmucosalimmunehomeostasisindssinducedcolitis
AT pengkun carnosolmaintainsintestinalbarrierfunctionandmucosalimmunehomeostasisindssinducedcolitis
AT gaoyanping carnosolmaintainsintestinalbarrierfunctionandmucosalimmunehomeostasisindssinducedcolitis
AT wangjinxia carnosolmaintainsintestinalbarrierfunctionandmucosalimmunehomeostasisindssinducedcolitis
AT gaocaiping carnosolmaintainsintestinalbarrierfunctionandmucosalimmunehomeostasisindssinducedcolitis
AT hechong carnosolmaintainsintestinalbarrierfunctionandmucosalimmunehomeostasisindssinducedcolitis
AT lufang carnosolmaintainsintestinalbarrierfunctionandmucosalimmunehomeostasisindssinducedcolitis