Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 28, 2016; 22(48): 10584-10591
Published online Dec 28, 2016. doi: 10.3748/wjg.v22.i48.10584
Regulating effect of TongXie-YaoFang on colonic epithelial secretion via Cl- and HCO3- channel
Cheng Yang, Ying Xiong, Sheng-Sheng Zhang, Fang-Mei An, Jing Sun, Qing-Lin Zhang, Qiang Zhan
Cheng Yang, Fang-Mei An, Jing Sun, Qing-Lin Zhang, Qiang Zhan, Department of Gastroenterology, Wuxi People’s Hospital, Nanjing Medical University, Wuxi 214023, Jiangsu Province, China
Ying Xiong, Community Health Service Center of Jinkui Street, Wuxi 214023, Jiangsu Province, China
Sheng-Sheng Zhang, Digestive Disease Diagnosis and Treatment Center, Beijing Chinese Medicine Hospital, Capital Medical University, Beijing 100010, China
Author contributions: Yang C made contributions to the study design, data interpretation, and wrote the manuscript; Zhang SS made contributions to the study design; Xiong Y, An FM, Sun J and Zhan Q performed the majority of experiments and data analysis; Zhang QL conducted the majority of quality control for the herbs of the formula.
Supported by Medical and public health technology research and development projects of WuXi science and technology development fund, No. CSE31N1501.
Institutional review board statement: All experiments were reviewed and approved by the Ethical Committee and Institutional Animal Care and Use Committee of Dongzhimen Hospital, No. SYXK(Beijing)2009.0028, and the methods were performed in strict accordance with the Animal Management Rules of the Chinese Ministry of Health.
Institutional animal care and use committee statement: All animal care and experimental procedures were conducted according to the institutional ethical guidelines and conformed to the requirements of the Institutional Animal Care and Use Committee of Beijing University of Chinese Medicine and the Animal Ethics Committee of Dongzhimen Hospital, No. SYXK(Beijing)2009.0028.
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Zhan Qiang, PhD, Associate Professor, Department of Gastroenterology, Wuxi People’s Hospital, Nanjing Medical University, 299 Qing-Yang Road, Nan-Chang District, Wuxi 214023, Jiangsu Province, China. zhanq33@163.com
Telephone: +86-510-85351120 Fax: +86-510-85351120
Received: August 23, 2016
Peer-review started: August 24, 2016
First decision: September 28, 2016
Revised: October 10, 2016
Accepted: November 15, 2016
Article in press: November 16, 2016
Published online: December 28, 2016
Abstract
AIM

To investigate the pharmacological effect of TongXie-YaoFang (TXYF) formula, a Chinese herbal formula, on Diarrhea-predominant irritable bowel syndrome (D-IBS) rats.

METHODS

In a neonatal maternal separation plus restraint stress (NMS + RS) model of D-IBS, male Sprague Dawley rats were randomly divided into two groups (NMS + RS group and TXYF-formula group) with no handlings were used as controls (NH group). Starting from postnatal day 60, rats in TXYF-formula group were administered TXYF-formula (4.92 g/100 g bodyweight) orally twice a day for 14 consecutive days while NH group and NMS + RS group were given distilled water. Using short-circuit current technology, we observed 5-HT-induced changes of current across ion channels, such as cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel, epithelial Na+ channel (ENaC), Ca2+-dependent Cl- channel (CACC), Na+-K+-2Cl- co-transporter (NKCC), and Na+-HCO3- co-transporter (NBC), in the colonic epithelium of three groups after exposure to drugs and specific blockers with a Power Lab System (AD Instruments International).

RESULTS

Under basal conditions, the changes of short-circuit current (∆Isc, µA/cm2) induced by 5-HT were similar in NH group and TXYF-formula group, and both higher than NMS + RS group (70.86 µA/cm2 ± 12.32 µA/cm2, 67.67 µA/cm2 ± 11.68 µA/cm2 vs 38.8 µA/cm2 ± 7.25 µA/cm2, P < 0.01, respectively). When CACC was blocked by 4,4′-diisothiocyanato-stilbene-2,2′-disulfonic acid, 5-HT-induced ∆Isc was smaller in NMS + RS group than in NH group and TXYF-formula group, respectively (48.41 µA/cm2 ± 13.15 µA/cm2 vs 74.62 µA/cm2 ± 10.73 µA/cm2, 69.22 µA/cm2 ± 11.7 µA/cm2, P < 0.05, respectively). The similar result could be obtained when ENaC was blocked by Amiloride (44.69 µA/cm2 ± 12.58 µA/cm2 vs 62.05 µA/cm2 ± 11.26 µA/cm2, 62.11 µA/cm2 ± 12.01 µA/cm2, P < 0.05, respectively). However, when CFTR Cl- channel was blocked by 1,1-dimethyl piperidinium chloride (DPC), 5-HT-induced ∆Isc did not significantly differ in three groups (42.28 µA/cm2 ± 10.61 µA/cm2 vs 51.48 µA/cm2 ± 6.56 µA/cm2 vs 47.75 µA/cm2 ± 7.99 µA/cm2, P > 0.05, respectively). The similar results could also be obtained in three groups when NBC and NKCC were respectively blocked by their blockers.

CONCLUSION

TXYF-formula can regulate the Cl- and HCO3- secretion of colonic mucosa via CFTR Cl- channel, Cl-/HCO3- exchanger, NBC and NKCC co-transporters.

Keywords: Ion channel, Diarrhea-predominant irritable bowel syndrome, Colonic mucosa, Short-circuit current, TongXie-YaoFang formula

Core tip: Diarrhea-predominant irritable bowel syndrome (D-IBS) is a chronic functional gastrointestinal disease. Abnormal ion secretion of colonic mucosal epithelial cells is recognized as one of the pathophysiological factors. In this paper, through the observation of TongXie-YaoFang (TXYF) formula, a Chinese herbal formula, to D-IBS rats obtained by neonatal maternal separation plus restraint stress. The mucosal stripping under a microscope was used for tissue preparation. Short-circuit current technology was used for testing 5-HT-induced changes in the current across ion channels of colonic epithelium. The results indicated that TXYF-formula could regulate the secretion of Cl- and HCO3- in colonic mucosa via cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel, Cl-/HCO3- exchanger, Na+-HCO3- co-transporter and Na+-K+-2Cl- co-transporter co-transporters.