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.
Highlights
Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders. e incidence of IBS has reached to 10–30% in the world; the incidence is still increasing year by year [1, 2]
Reduced Abdominal withdrawal reflex (AWR) pain threshold was observed in diarrhea predominant IBS (D-IBS) rats when compared with the control group, while this decreased AWR scale could be rescued by the utilization of QingHuaZhiXie prescription, and the effect was statistically significant (P < 0.05)
The therapeutic effect of QingHuaZhiXie prescription on D-IBS was positively correlated with its dosage during treatment, and the highest AWR threshold of rats was observed in the high dosage group when compared with that of low and medium dosage (P < 0.05) (Figure 1(a))
Summary
Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders. e incidence of IBS has reached to 10–30% in the world; the incidence is still increasing year by year [1, 2]. Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders. Numerous factors have been shown to be associate with D-IBS, such as brain-gut axis dysfunction, intestinal flora disorder, intestinal bacterial infection, gastrointestinal motility disorder, visceral hypersensitivity, and so on. The pathogenesis of D-IBS is complex, and its pathophysiological mechanism is still unclear [5, 6]. The importance of the immune inflammatory model in the D-IBS pathogenesis was focused. In response to D-IBS, the TLR4/MyD88/NF-κB pathway, composing of TLR4, myeloid differentiation factor 88 (MyD88), and nuclear factor-κB (NF-κB), can transmit inflammatory signals to inflammatory cytokines such as IFN-c and TNFα, causing imbalanced expression of inflammatory cytokines, leading to inflammatory response, and affecting gastrointestinal motility, secretion, and sensitivity [5, 7,8,9]
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