Abstract
The aim of this study was to investigate the precise clinical use of Sinitang decoction (SNT) in ulcerative colitis (UC). Network pharmacology-based analysis of the drug components–targets–diseases–pathways was used to predict the possible clinical applications of SNT. Next, 2,4,6-trinitrobenzenesulfonic acid (TNBS) was used to establish a rat model of UC, and the efficacy of SNT against UC was tested, followed by a proteomic analysis of the specific signatures regulated by SNT against UC. SNT was predicted to be effective in inflammatory bowel disease, UC, and several other diseases. In the rats with UC, SNT decreased the disease activity index and colon mucosal damage index compared to the untreated UC model rats. Additionally, SNT reversed the upregulated levels of serum tumor necrosis factor (TNF)-α, prostaglandin E2 (PGE2), interleukin (IL)-6, and nitric oxide (NO) in UC model rats. The proteomic analysis identified 78 proteins that were differentially regulated by SNT in the rats with UC, which were associated with the Gene Ontology terms sulfur compound binding, calcium ion binding, and Toll-like receptor (TLR)-4 binding. Among these differentially regulated proteins, C-reactive protein (CRP) and collagen alpha-1(XII) chain (COL12A1) were found to be signature proteins associated with the efficacy of SNT against UC. This study represents the first precise investigation of the efficacy and mechanisms of SNT against UC, and shows that SNT is a promising candidate for personalized management of UC.
Highlights
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon that involves abdominal pain, diarrhea, and hematochezia (Thorsteinsdottir et al, 2011; Eisenstein, 2018)
The TTD analysis indicated that Sinitang decoction (SNT) was involved in inflammation (18 targets), inflammatory diseases (10 targets), inflammatory bowel disease (6 targets), and UC (5 targets), but only UC was significantly relevant (Figure 1A, Table S1), while both the OMIM (Figure 1B) and DAVID (Figure 1C) analyses showed that SNT may affect colorectal and gastric cancer
The experimental results based on rats indicated that SNT can improve the symptoms of UC, exerting beneficial pharmacological effects against UC
Summary
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon that involves abdominal pain, diarrhea, and hematochezia (Thorsteinsdottir et al, 2011; Eisenstein, 2018). Several drugs, such as aminosalicylates, have been used to ease some of the symptoms of UC, but they have failed to make a remarkable breakthrough to improve the overall clinical picture, and advanced treatments remain urgently needed (Ungaro et al, 2016). SNT has been shown to improve the symptoms of various intestinal diseases, such as inflammatory bowel disease (Pei et al, 2015), diarrhea and irritable bowel syndrome (Chu, 2016; Xi and Wu, 2018), constipation (Zhu, 2016), intestinal mucosal injury (Kexuan et al, 2016), and postoperative intestinal adhesion (Hou, 2004). Some effort has been made to understand the mechanisms of SNT, there remains a need to precisely investigate its efficacy and mechanisms
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