Schisandrin C improves leaky gut conditions in intestinal cell monolayer, organoid, and nematode models by increasing tight junction protein expression

封堵器 紧密连接 细胞生物学 肠道通透性 化学 肠上皮 生物 分子生物学 上皮 免疫学 遗传学
作者
Mi Ri Kim,Su-Yeon Cho,Hee Ju Lee,Joo Yeon Kim,Uyen Tran Tu Nguyen,Ngoc Minh Ha,Ki Young Choi,Kwang Hyun,Jeong‐Ho Kim,Won Kyu Kim,Kyungsu Kang
出处
期刊:Phytomedicine [Elsevier BV]
卷期号:103: 154209-154209 被引量:25
标识
DOI:10.1016/j.phymed.2022.154209
摘要

Leaky gut symptoms and inflammatory bowel disease (IBD) are associated with damaged intestinal mucosa, intestinal permeability dysfunction by epithelial cell cytoskeleton contraction, disrupted intercellular tight junction (TJ) protein expression, and abnormal immune responses and are intractable diseases.We evaluated the effects of schisandrin C, a dibenzocyclooctadiene lignan from Schisandra chinensis, on intestinal inflammation and permeability dysfunction in gut mimetic systems: cultured intestinal cells, intestinal organoids, and a Caenorhabditis elegans model.Schisandrin C was selected from 9 lignan compounds from S. chinensis based on its anti-inflammatory effects in HT-29 human intestinal cells. IL-1β and Pseudomonas aeruginosa supernatants were used to disrupt intestinal barrier formation in vitro and in C. elegans, respectively. The effects of schisandrin C on transepithelial electrical resistance (TEER) and intestinal permeability were evaluated in intestinal cell monolayers, and its effect on intestinal permeability dysfunction was tested in mouse intestinal organoids and C. elegans by measuring fluorescein isothiocyanate (FITC)-dextran efflux. The effect of schisandrin C on TJ protein expression was investigated by western blotting and fluorescence microscopy. The signaling pathway underlying these effects was also elucidated.Schisandrin C ameliorated intestinal permeability dysfunction in three IBD model systems and enhanced epithelial barrier formation via upregulation of ZO-1 and occludin in intestinal cell monolayers and intestinal organoids. In Caco-2 cells, schisandrin C restored IL-1β-mediated increases in MLCK and p-MLC expression, in turn blocking cytoskeletal contraction and subsequent intestinal permeabilization. Schisandrin C inhibited NF-ĸB and p38 MAPK signaling, which regulates MLCK expression and structural reorganization of the TJ complex in Caco-2 cells. Schisandrin C significantly improved abnormal FITC-dextran permeabilization in both intestinal organoids and C. elegans.Schisandrin C significantly improves abnormal intestinal permeability and regulates the expression of TJ proteins, long MLCK, p-MLC, and inflammation-related proteins, which are closely related to leaky gut symptoms and IBD development. Therefore, schisandrin C is a candidate to treat leaky gut symptoms and IBDs.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
刚刚
lzy发布了新的文献求助10
1秒前
2秒前
xc41992完成签到,获得积分10
2秒前
tian发布了新的文献求助10
2秒前
2秒前
3秒前
可爱小菜完成签到,获得积分10
4秒前
5秒前
hopen发布了新的文献求助10
5秒前
汉堡发布了新的文献求助10
6秒前
NN123完成签到,获得积分10
6秒前
7秒前
sunny完成签到 ,获得积分10
8秒前
nino应助万万想到了采纳,获得20
8秒前
yuchengZ发布了新的文献求助10
9秒前
evidence完成签到,获得积分10
9秒前
9秒前
练习者发布了新的文献求助10
9秒前
NN123发布了新的文献求助10
10秒前
10秒前
xu发布了新的文献求助10
10秒前
10秒前
11秒前
夜夜夜应助sophie采纳,获得10
11秒前
11秒前
冷静新烟发布了新的文献求助10
12秒前
科研通AI5应助yl采纳,获得10
12秒前
好好学习完成签到,获得积分10
13秒前
杨gj发布了新的文献求助10
13秒前
hopen完成签到,获得积分10
13秒前
阴阳饱饱发布了新的文献求助10
15秒前
15秒前
最佳完成签到 ,获得积分10
16秒前
16秒前
16秒前
cdercder应助白水采纳,获得10
17秒前
科研通AI2S应助杨gj采纳,获得10
17秒前
卷怕了发布了新的文献求助10
17秒前
高分求助中
【此为提示信息,请勿应助】请按要求发布求助,避免被关 20000
Encyclopedia of Geology (2nd Edition) 2000
CRC Handbook of Chemistry and Physics 104th edition 1000
Izeltabart tapatansine - AdisInsight 600
An International System for Human Cytogenomic Nomenclature (2024) 500
Introduction to Comparative Public Administration Administrative Systems and Reforms in Europe, Third Edition 3rd edition 500
Distinct Aggregation Behaviors and Rheological Responses of Two Terminally Functionalized Polyisoprenes with Different Quadruple Hydrogen Bonding Motifs 450
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 物理 生物化学 纳米技术 计算机科学 化学工程 内科学 复合材料 物理化学 电极 遗传学 量子力学 基因 冶金 催化作用
热门帖子
关注 科研通微信公众号,转发送积分 3765463
求助须知:如何正确求助?哪些是违规求助? 3309974
关于积分的说明 10152973
捐赠科研通 3025346
什么是DOI,文献DOI怎么找? 1660499
邀请新用户注册赠送积分活动 793353
科研通“疑难数据库(出版商)”最低求助积分说明 755565