Mume Fructus Restores Intestinal Mucosal Epithelial Barrier Through MEK/ERK Signaling Pathway in Mouse Model of Inflammatory Bowel Disease
10.13422/j.cnki.syfjx.20250540
- VernacularTitle:乌梅通过MEK/ERK信号通路修复炎症性肠病小鼠肠黏膜上皮屏障功能
- Author:
Huachen LIU
1
;
Chonghao ZHANG
1
;
Yalan LI
1
;
Jie LIU
1
;
Jialong SU
1
;
Na LI
1
;
Shaoshuai LIU
2
;
Qing WANG
1
;
Guiying PENG
1
Author Information
1. School of Life Sciences， Beijing University of Chinese Medicine， Beijing 100029， China
2. Beijing Jiangong Hospital， Beijing 100031， China
- Publication Type:Journal Article
- Keywords:
Mume Fructus;
inflammatory bowel disease;
mitogen-activated protein kinase kinase （MEK）;
extracellular signal-regulated kinase （ERK）;
tight junction proteins
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(20):76-85
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo clarify the repair effect of Mume Fructus on the intestinal mucosal epithelial barrier in the mouse model of inflammatory bowel disease （IBD） and explore the repair mechanism. MethodsThirty-six male C57BL/6 mice were randomly assigned into six groups： normal， model， low-， medium-， and high-dose （200， 400， and 800 mg·kg-1） Mume Fructus， and sulfasalazine （300 mg·kg-1）. Except the normal group， the rest groups had free access to 2% dextran sulfate sodium （DSS） solution for seven days to establish the IBD model， followed by a seven-day drug intervention. The body weight change and disease activity index （DAI） were recorded. After the last administration， spleen and colon tissue samples were collected to analyze the differences in colon length and spleen index. Hematoxylin-eosin staining was used to observe the morphology of the colon tissue. The level of diamine oxidase （DAO） in the serum was measured by the DAO assay kit. Immunohistochemistry was employed to determine the expression of tight junction proteins such as Claudin-1， Occludin， and zonula occludens-1 （ZO-1） in the colon tissue. Real-time PCR was performed to measure the mRNA levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in the colon tissue. Finally， Western blot was employed to determine the protein levels of mitogen-activated protein kinase kinase （MEK）， extracellular signal-regulated kinase （ERK）， phosphorylated （p）-MEK， and phosphorylated ERK in the colon tissue. ResultsCompared with the normal group， the model group exhibited decreases in body weight and colon length （P<0.01）， increases in DAI， spleen index， and serum DAO level （P<0.01）， damaged colonic epithelium and goblet cells， and obvious infiltration of inflammatory cells. In addition， the model group exhibited higher positive expression of Claudin-1， Occludin， and ZO-1 （P<0.01）， higher mRNA levels of TNF-α and IL-1β （P<0.01）， and higher protein levels of p-MEK and p-ERK （P<0.05， P<0.01） than the normal group. However， sulfasalazine and three doses of Mume Fructus markedly decreased the body weight and DAI （P<0.05）， recovered the colon length and spleen index， alleviated colon tissue damage， lowered the level of DAO in the serum （P<0.01）， and down-regulated the mRNA levels of TNF-α and IL-1β （P<0.01） and the protein levels of p-MEK and p-ERK （P<0.05）. Sulfasalazine and low- and medium-dose Mume Fructus increased the positive expression of Occludin， Claudin-1， and ZO-1 （P<0.05， P<0.01）. Furthermore， high-dose Mume Fructus elevated the protein expression of Occludin （P<0.05）. ConclusionMume Fructus can restore the expression of intestinal epithelial tight junction proteins by inhibiting the phosphorylation of proteins in the MEK/ERK signaling pathway and down-regulating the levels of TNF-α and IL-1β， thus repairing the intestinal mucosal barrier in the mouse model of IBD.
