Effect of TongXie-YaoFang on Cl(-) and HCO3 (-) Transport in Diarrhea-Predominant Irritable Bowel Syndrome Rats.

Xiaofang Lu,Zhenyu Wu,Jing Xie,Luqing Zhao,Cheng Yang,Shengsheng Zhang,Zhengfang Wang

doi:10.1155/2016/7954982

Abstract

TongXie-YaoFang (TXYF) can effectively alleviate the symptoms of diarrhea-predominant irritable bowel syndrome (D-IBS) patients. However, the curative mechanism has not been fully clarified. The study was designed to investigate the effect of TXYF on the colonic ion transport induced by serotonin (5-HT) in D-IBS rats. A method of multiple stress (neonatal maternal separation (NMS) combined with restraint stress (RS)) was used to induce the D-IBS model. The model rats were randomly divided into two groups: NMS + RS group and TXYF-formula group, and the normal control (no handling) rats were classified as NH group. In the NMS + RS group, the change of short-circuit current (ΔI sc) induced by 5-HT was lower than that in the NH and TXYF-formula groups. After removing of the extracellular Cl− or HCO3 − or basolateral Na+ or blocking the cystic fibrosis transmembrane conductance regulator (CFTR), Na+-K+-2Cl− cotransporter (NKCC), Na+-HCO3 − cotransporter, Cl−/HCO3 − exchanger, K+ channel, or Na+/K+-ATPase, respectively, there was no difference in 5-HT-induced ΔI sc among the three groups. These data suggest that TXYF can regulate 5-HT-induced Cl− and HCO3 − secretion, possibly mediated by the combined action of CFTR, NKCC, Na+-HCO3 − cotransporter, Cl−/HCO3 − exchanger, K+ channel, and Na+/K+-ATPase.

Highlights

Diarrhea-predominant irritable bowel syndrome (D-IBS) is a chronic functional gastrointestinal disease, which is characterized by abdominal pain/discomfort and diarrhea without the demonstrable pathological evidence according to Rome III criteria [1]
After addition of 5-HT (10 μmol L−1) in the basolateral side, ΔIsc in the Neonatal Maternal Separation (NMS) + Restraint Stress (RS) group was reduced more than that in the NH group; after treatment with TXYF, ΔIsc in the TXYF-formula group was significantly increased compared with the NMS + RS group (P < 0.01, Figure 1(d))
From K-HS, 5-HT-induced ΔIsc was lower in the NMS + RS group compared with the NH group (P < 0.01, Figure 2(b)) and TXYF-formula group (P < 0.05, Figure 2(b))

Summary

Introduction

Diarrhea-predominant irritable bowel syndrome (D-IBS) is a chronic functional gastrointestinal disease, which is characterized by abdominal pain/discomfort and diarrhea without the demonstrable pathological evidence according to Rome III criteria [1]. As a multifactorial disease, the pathogenesis of D-IBS is complex and has not been fully understood as yet. The therapeutic effect has not been satisfactory for patients, multiple medications have been developed as the optional therapies including loperamide, bile acid sequestrants, antispasmodics, tricyclic antidepressants, and rifaximin [4,5,6,7,8,9]. A series of randomized controlled trials have shown that Traditional Chinese Medicine (TCM) such as the representative formula TongXie-YaoFang (TXYF) can significantly alleviate the symptoms and improve the quality of life in D-IBS patients [10, 11]. The mechanism of the therapeutic effect has not been known, which limits the application of TXYF on a larger scale

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