A Network Pharmacological Approach to Explore the Mechanisms of TongXieYaoFang in Inflammatory Bowel Disease

Abstract Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the intestine, demonstrating an increasing incidence every year. TongXieYaoFang (TXYF) has been used widely in China as a complementary therapy to relieve the symptoms of IBD for hundreds of years. In the present research, a network pharmacology-based approach was used to systematically explore the intrinsic mechanisms of TXYF in IBD at the molecular level. Network pharmacology-based methods, which mainly included database mining, screening of bioactive compounds, target prediction, collection of IBD-related targets, gene enrichment analysis, network construction, and molecular docking, were employed in the present study. Network analysis revealed a total of 108 potential targets derived from 22 component compounds of TXYF, among which 34 targets were common with the IBD-related targets. In the protein-protein interaction (PPI) network, 10 key targets were identified. The gene enrichment analysis suggested that anti-inflammatory processes, such as NF-kappa B signaling pathway and Toll-like receptor signaling pathway, could be the core processes involved in the action of TXYF in IBD. Molecular docking results revealed that three compounds present in TXYF exhibited strong binding affinity for PTGS2. The present study provides novel insights into the molecular mechanisms and network approaches of TXYF action in IBD from a systemic perspective. The potential targets and pathways identified in the present study would assist in further research on the clinical application of TXYF in IBD therapy.

Regulation of Colonic Mucosal MicroRNA Expression via Multiple Targets in Visceral Hypersensitivity Rats by Tongxieyaofang

PURPOSE: This study aimed to screen for differentially expressed microRNAs (miRNAs) in the colons of rats with visceral hypersensitivity to build the expression profiles of miRNAs therein and to determine the mechanism of Tongxieyaofang use in the treatment of irritable bowel syndrome (IBS). MATERIALS AND METHODS: Forty Sprague-Dawley rats were divided randomly into four groups: control group, model control group (induced by rectum stimulus and evaluated by abdominal withdraw reaction), treatment control group (normal saline), and Tongxieyaofang group (treated with Tongxieyaofang). We screened for differential expression of colonic mucosal miRNAs using liquid chip technology and verified the expression thereof using reverse transcription-PCR. RESULTS: The visceral hypersensitivity rat model was successfully established. We found the expression of let-7f, let-7i, miR-130b, miR-29a, miR-132, miR-21, and miR-375 to be up-regulated (p < 0.05), while the expression of miR-24, miR-31a, miR-192, miR-221, and miR-223 was down-regulated (p < 0.05) in the visceral hypersensitivity rats. After treatment with Tongxieyaofang, the expression of let-7f, let-7i, miR-130b, miR-29a, miR-132, miR-21, and miR-375 was reduced (p < 0.05), whereas the expression of miR-24, miR-31a, miR-192, miR-221, miR-223 was increased, compared to the treatment control group (p < 0.05). CONCLUSION: MiRNAs play a pivotal role in visceral hypersensitivity and might be targets in the treatment of IBS by Tongxieyaofang.

Treatment of Irritable Bowel Syndrome with Modified TongXieYaoFang: A 83 Cases Study / 国际中医中药杂志

Objective To study the effects of treating irritable bowel syndrome (IBS) with modified TongXieYaoFang. Methods 83 IBS patients were randomly recruited into a treatment group (45 patients) and a control group (38 patients). In the control group, Trimebutine, 200mg, and Bifid triple viable capsule, 420mg, 3 times/day was given orally to the patients, while on the basis of that, the treatment group was administrated with modified TongXieYaoFang in addition. Both groups were treated for one course of 4 weeks. Results The total effective rate of the treatment group and the control group was 93.3% and 71.1% respectively, showing significant difference between the two groups (X2=7.2938, P<0.01 ). Conclusion TongXieYaoFang combined with western medicine is effective in treating IBS.

Mechanism of Tongxieyaofang on irritable bowel syndrome / 中草药

Objective To study the effect and the mechanism of Tongxieyaofang (TXYF) on rat model of irritable bowel syndrome (IBS). Methods Model rats of IBS which were prepared by chronic stimulation in colon were randomly divided into groups: the normal control group (Group A), the model control group (Group B), the positive control group (Group C), the low dosage of TXYF group (Group D), the high dosage of TXYF group (Group E). Different treatments were given to every groups by ig administration for one month. The capability limens of the sacculus that caused abdomen-uplifting and back-arching and the times of contract of abdomen muscle in rats under different dilatations were observed. The levels of 5-hydroxytryptamine (5-HT), substance P (SP), and calcitonin gene related peptide (CGRP) were evaluated. Results Compared with the Group B, the TXYF could effectively improve the index of the behavior and electrophysiology, it also could lower the levels of 5-HT and SP, and increase the levels of CGRP of rat model of IBS with certain dose-effect relationship. Conclusion TXYF could lower the levels of 5-HT in serum and SP in plasma, and increase CGRP level of model rats of IBS, especially in high dosage. The mechanism of TXYF may be increasing the pain threshold of bowel, eliminating hypersusceptibility of bowel, and decreasing excitability of nerve cells by decreasing the 5-HT and SP levels in IBS rats.