结肠炎
免疫印迹
SOCS3
封堵器
炎症
药理学
车站3
医学
粘合连接
免疫学
紧密连接
生物
信号转导
细胞
生物化学
钙粘蛋白
基因
作者
Zhe Cheng,Yi Zhou,Xinyu Xiong,Lingli Li,Zekai Chen,Fan Wu,Ruolan Dong,Qiong Liu,Zhao Yan,Shujun Jiang,Qin Yu,Guang Chen
出处
期刊:Phytomedicine
[Elsevier]
日期:2024-04-01
卷期号:126: 155283-155283
被引量:1
标识
DOI:10.1016/j.phymed.2023.155283
摘要
Portulacae Herba and Granati Pericarpium pair (PGP) is a traditional Chinese herbal medicine treatment for colitis, clinically demonstrating a relatively favorable effect on relieving diarrhea and abnormal stools. However, the underlying mechanisms remain uncertain. The present study intends to evaluate the efficacy of PGP in treating colitis in mice and investigate its underlying mechanism. The protective effect of PGP against colitis was determined by monitoring body weight, colon length, colon weight, and survival rate in mice. Colonic inflammation was assessed by serum cytokine levels, colonic H&E staining, and local neutrophil infiltration. The reversal of intestinal epithelial barrier damage by PGP was subsequently analyzed with Western blot and histological staining. Furthermore, RNA-seq analysis and molecular docking was performed to identify potential pathways recruited by PGP. Following the hints of the transcriptomic results, the role of PGP through the IL-6/STAT3/SOCS3 pathway in DSS-induced colitis mice was verified by Western blot. DSS-induced colitis in mice was significantly curbed by PGP treatment. PGP treatment significantly mitigated DSS-induced colitis in mice, as evidenced by improvements in body weight, DAI severity, survival rate, and inflammatory cytokines levels in serum and colon. Moreover, PGP treatment up-regulated the level of Slc26a3, thereby increasing the expressions of the tight junction/adherens junction proteins ZO-1, occludin and E-cadherin in the colon. RNA-seq analysis revealed that PGP inhibits the IL-6/STAT3/SOCS3 pathway at the transcriptional level. Molecular docking indicated that the major components of PGP could bind tightly to the proteins of IL-6 and SOCS3. Meanwhile, the result of Western blot revealed that the IL-6/STAT3/SOCS3 pathway was inhibited at the protein level after PGP administration. PGP could alleviate colonic inflammation and reverse damage to the intestinal epithelial barrier in DSS-induced colitis mice. The underlying mechanism involves the inhibition of the IL-6/STAT3/SOCS3 pathway.
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