Abstract
Objective Tong Xie Yao Fang (TXYF) is a classic and effective prescription in traditional Chinese medicine which is used to treat ulcerative colitis (UC). Our study investigated the effect of TXYF on Hippo pathway activation in UC-induced intestinal mucosa injury and explored the possible mechanism. Method After ulcerative colitis was successfully induced by trinitrobenzene sulfonic acid (TNBS), 48 Sprague Dawley (SD) rats were randomly divided into a control group, model group, TXYF group, and sulfasalazine group and treated with the corresponding drugs for 28 days. The parameters including body weight, colon length, spleen index, and disease activity index (DAI) and histopathological characteristics were assessed. The myeloperoxidase (MPO) activity and IL-6 level in the colon mucosa were determined with the corresponding commercial kits. The expressions of the Hippo pathway components YAP1, TAZ, P-YAP, and LATS1 were detected in the colon mucosa of each group on different stages by quantitative real-time PCR (qRT-PCR) and western blotting. Immunohistochemical staining was used to evaluate the growth and apoptosis of the colon epithelium. Result TXYF significantly improved the weight loss, colonic shortening, DAI, spleen enlargement, and histopathological score of the rats with TNBS-induced UC. TXYF also reduced the MPO activity and expression of IL-6 in the colon mucosa. Furthermore, treatment with TXYF significantly increased YAP1 expression in the early stage (3–7 days) and significantly decreased YAP1 expression in the late stage (14–28 days). In the early stage, TXYF inhibited Hippo pathway activity, which promoted proliferation and regeneration of the intestinal mucosa. In the late stage, the Hippo pathway was activated, thereby inhibiting apoptosis and promoting intestinal mucosal differentiation. Conclusion TXYF alleviated the inflammatory response and promoted mucosal healing in rats with UC, which was probably achieved through the Hippo pathway. These results indicated that TXYF was a potential therapy for treating UC.
Highlights
ulcerative colitis (UC) is a chronic inflammatory bowel disease whose aetiology and pathogenesis are unclear. e disease usually affects the mucosa and submucosa of the colon and/or rectum
A rat model of trinitrobenzene sulfonic acid (TNBS)-induced UC was used to evaluate the treatment of Tong Xie Yao Fang (TXYF). e body weight of each experimental rat was approximately the same
After 22 days, the weight gain of the rats treated with TXYF was significantly higher than that of the rats treated with sulfasalazine (Figure 1(a))
Summary
UC is a chronic inflammatory bowel disease whose aetiology and pathogenesis are unclear. e disease usually affects the mucosa and submucosa of the colon and/or rectum. UC is a chronic inflammatory bowel disease whose aetiology and pathogenesis are unclear. E disease usually affects the mucosa and submucosa of the colon and/or rectum. E predominant symptoms and characteristics of this disease include frequent abdominal pain, bloody diarrhoea, constipation, and fatigue, and these symptoms seriously affect the normal work and lives of patients. Colorectal cancer is related to long-term chronic intestinal inflammation [3,4,5]. There is no specific clinical treatment for UC because its mechanism of pathogenesis is unknown. Conventional medications that contain amino salicylic acid, immunosuppressive agents, and biological agents can alleviate UC, the long-term use of these agents often leads to side effects such as upper gastrointestinal bleeding, vomiting, nausea, headaches, and rashes. Some patients are nonresponsive to such drugs [6]. erefore, scientists have started to identify alternative and complementary medicines, especially natural medicines with fewer side effects [7, 8]
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