Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 14, 2015; 21(10): 2912-2917
Published online Mar 14, 2015. doi: 10.3748/wjg.v21.i10.2912
Inhibitory effect of TongXie-YaoFang formula on colonic contraction in rats
Cheng Yang, Sheng-Sheng Zhang, Xiao-Ling Li, Zheng-Fang Wang, Lu-Qing Zhao
Cheng Yang, Sheng-Sheng Zhang, Zheng-Fang Wang, Lu-Qing Zhao, Digestive Disease Diagnosis and Treatment Center, Beijing Chinese Medicine Hospital, Capital Medical University, Beijing 100010, China
Xiao-Ling Li, Basic Medicine College, Beijing University of Chinese Medicine, Beijing 100010, China
Author contributions: Yang C contributed to the study design and data interpretation, and wrote the manuscript; Zhang SS contributed to the study design; Li XL performed the majority of experiments and data analysis; Wang ZF and Zhao LQ contributed to the majority of quality control for the herbs of the formula.
Supported by National Nature Science Foundation of China, No. 81473644; the Clinical Medicine Development Project of Beijing Municipal Administration of Hospitals, No. ZY201411; the Project of Health Technical Personnel of the Beijing Health System, No. 2011-2-13.
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: Sheng-Sheng Zhang, PhD, Professor, Digestive Disease Diagnosis and Treatment Center, Beijing Chinese Medicine Hospital, Capital Medical University, 23 Meishuguanhou Street, Dongcheng District, Beijing 100010, China. zhss2000@163.com
Telephone: +86-10-52176634 Fax: +86-10-52176634
Received: July 31, 2014
Peer-review started: August 2, 2014
First decision: August 27, 2014
Revised: September 20, 2014
Accepted: November 30, 2014
Article in press: December 1, 2014
Published online: March 14, 2015
Abstract

AIM: To investigate the pharmacological effect of TongXie-YaoFang (TXYF) formula and its underlying mechanisms.

METHODS: A neonatal maternal separation plus restraint stress (NMS + RS) model of diarrhea-predominant irritable bowel syndrome was developed by subjecting male Sprague-Dawley rats to daily maternal separation from postnatal days 2 to 21 plus restraint stress from days 50 to 59. Rats were randomly divided into two groups (NMS + RS and TXYF formula), and rats with no handling or separation were used as normal controls. Starting from postnatal day 60, rats were administered TXYF formula (9.84 g/100 g body weight) orally twice daily for 14 consecutive days, while the normal and NMS + RS groups were given distilled water. The distinctions of movement index (MI, area under the curve of contraction intensity/min, mg/min) and contraction frequency (CF, number of contractions/min, times/min) of isolated colonic longitudinal smooth muscle strips (CLSMs) in the three groups before and after treatment were observed with a Power Lab system. Different inhibitors were applied, and then 10-4 mol/L acetylcholine chloride (Ach) was added to CLSMs to induce muscle contraction.

RESULTS: Before treatment, the MI of CLSMs in the NMS + RS and TXYF formula groups was similar and both higher than that in the normal group (545.49 ± 73.66 mg/min vs 245.76 ± 34.44 mg/min and 551.09 ± 54.29 mg/min vs 245.76 ± 34.44 mg/min, P < 0.01, respectively). After treatment, the MI in the TXYF formula group was lower than that in the NMS + RS group (261.39 ± 38.59 mg/min vs 533.9 ± 61.63 mg/min, P < 0.01). In the same way, the CF of CLSMs in the NMS + RS and TXYF formula groups was similar and both higher than that in the normal group (3.42 ± 0.25 times/min and 3.31 ± 0.21 vs 1.1 ± 0.17 times/min, P < 0.01) before treatment. After treatment, the CF in the TXYF formula group was lower than that in the NMS + RS group (1.42 ± 0.87 times/min vs 3.11 ± 0.82 times/min, P < 0.01) and similar to that in the normal group (1.42 ± 0.87 times/min vs 1.09 ± 0.13 times/min). When 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride and 4-aminopyridine were added to the bath and equilibrated for 30 min, respectively, and 10-4 mol/L Ach was added to CLSMs to induce muscle contraction, MI of the CLSMs in the TXYF formula group was lower than that in the normal group (666 ± 36.32 mg/min vs 747.77 ± 49.47 mg/min, and 686.53 ± 39.17 mg/min vs 750.45 ± 29.39 mg/min; P < 0.01, respectively). The MI of CLSMs in the TXYF formula group was lower than that in the normal group after treatment with nifedipine (689.48 ± 30.84 mg/min vs 741.65 ± 32.41 mg/min; P < 0.05).

CONCLUSION: TXYF formula inhibits colon contraction in rats. This may be related to activation of specific potassium channels and inhibition of extracellular calcium internal flow.

Keywords: Irritable bowel syndrome, Neonatal maternal separation, Herbal medicine, Colonic longitudinal smooth muscle, Potassium channel

Core tip: Diarrhea-predominant irritable bowel syndrome (D-IBS) is a chronic gastrointestinal disease that seriously affects quality of life. Colon dysmotility is recognized as one of the pathophysiological factors. TongXie-YaoFang formula can effectively relieve diarrhea and lower visceral hypersensitivity in D-IBS rats, mainly via inhibiting the amplitude and frequency of colonic longitudinal smooth muscle contraction. Its action of mechanism may be related to the activation of specific potassium channels, inhibition of extracellular calcium internal flow, and reduction of intracellular free Ca2+ concentration.