Mechanism of QingHuaZhiXie Prescription Regulating TLR4-IECs Pathway in the Intervention of Diarrhea Predominant Irritable Bowel Syndrome

Abstract

To investigate the effect and mechanism of QingHuaZhiXie prescription on diarrhea predominant irritable bowel syndrome (D-IBS), animal models of rats were used in this study. 48 rats were randomly divided into 6 groups, containing one control group, one animal model group (D-IBS group), and four drug intervention groups (low, medium, and high dosage of QingHuaZhiXie prescription and trimebutine maleate intervention group). Abdominal withdrawal reflex (AWR) and Bristol stool form scale were recorded; the expression levels of inflammatory factors (TNF-α and IFN-γ), pathway proteins TLR4, MyD88, NF-κB, and key proteins of tight junction between intestinal epithelial cells (IECs) were detected; the microstructure of intestinal mucosal was observed by hematoxylin and eosin (H&E) staining; MPO activity was detected with immunohistochemical analysis to reflect the inflammation of tissues. Results show that QingHuaZhiXie prescription reduced diarrhea index and intestinal hypersensitivity and intestinal tissue integrity after intervention. MPO activity in QingHuaZhiXie prescription-treated rats was significantly lower relative to their model group. The expression levels of inflammatory factors and TLR4/MyD88/NF-κB pathway proteins were repressed, and the protein levels of occludin and claudin-1 increased. Meanwhile, this study also found that the remission effect of QingHuaZhiXie prescription on D-IBS increased with its dosage increase. Hence, as a therapeutic prescription for D-IBS, QingHuaZhiXie prescription could relieve D-IBS symptoms through balancing the inflammatory factors expression by inhibiting the TLR4/MyD88/NF-κB pathway and maintaining the function and structure of IECs by improving the protein levels of JAM, occludin, claudin-1, and ZO-1.

Global Research Trends in Irritable Bowel Syndrome: A Bibliometric and Visualized Study

“…The TLR4-MyD88-transforming growth factor β-activated kinase1-NF-kB pathway is induced by wogonin to suppress inflammatory response and the down-regulation of CLDN-1 and ZO-1 in Caco-2 cells ( 102 ). IBS-D rats treated with QingHuaZhiXie prescription, a Chinese herbal compound prescription, showed that occludin, CLDN-1 and ZO-1 expression were restored in colon tissue by inhibiting the TLR4/MyD88/NF-κB pathway, which is accompanied by the improved symptoms of diarrhea and intestinal hypersensitivity ( 103 ).…”

Epithelial Barrier Dysfunction in Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D) via Downregulation of Claudin-1

“…The identification of individual cytokines responsible for barrier dysfunction in IBS-D will enable new therapeutic options. In this way, Huang and co-workers were able to identify a herbal mixture called "QingHuaZhiXie", which suppressed inflammatory factors and TLR4/MyD88/NF-κB pathway proteins, ultimately leading to increased protein levels of occludin and claudin-1 [33].…”