Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 28, 2015; 21(16): 4852-4863
Published online Apr 28, 2015. doi: 10.3748/wjg.v21.i16.4852
Alterations in serotonin, transient receptor potential channels and protease-activated receptors in rats with irritable bowel syndrome attenuated by Shugan decoction
Hai-Lian Shi, Chu-Hsuan Liu, Li-Li Ding, Yu Zheng, Xiao-Yan Fei, Lu Lu, Xue-Ming Zhou, Jian-Ye Yuan, Jian-Qun Xie
Hai-Lian Shi, Chu-Hsuan Liu, Yu Zheng, Xiao-Yan Fei, Lu Lu, Jian-Ye Yuan, Jian-Qun Xie, Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
Hai-Lian Shi, Li-Li Ding, Institute of Chinese Materia Medica, Shanghai Key Laboratory of Complex Prescription, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Xue-Ming Zhou, Experimental Animal Center, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Author contributions: Shi HL and Liu CH carried out all the experiments, analyzed the data and wrote the paper, and contributed equally to this study; Ding LL performed the HPLC analysis; Yuan JY and Xie JQ designed the experiments, analyzed the data, revised the paper, and contributed equally to this study; Zheng Y, Fei XY, Lu L and Zhou XM performed parts of the experiments and provided valuable suggestions for this study; all authors have read and approved the final manuscript.
Supported by Innovation Program of the Shanghai Municipal Education Commission, No. 12YZ065; National Natural Science Foundation of China, No. 81072786, No. 81473630 and No. 81202665; Longhua Medical Project, No. D-09; High level Project of the University of Educational Commission of Shanghai, China, No. 2008GSP19; and Shanghai Leading Academic Discipline Project, No. J50305.
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:
Correspondence to: Jian-Ye Yuan, Associate Professor, Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 530 Lingling Road, Xuhui District, Shanghai 200032, China.
Telephone: +86-21-64385700 Fax: +86-21-64398310
Received: September 22, 2014
Peer-review started: September 24, 2014
First decision: October 29, 2014
Revised: December 7, 2014
Accepted: January 30, 2015
Article in press: January 30, 2015
Published online: April 28, 2015

AIM: To determine the molecular mechanisms of Shugan decoction (SGD) in the regulation of colonic motility and visceral hyperalgesia (VHL) in irritable bowel syndrome (IBS).

METHODS: The chemical compounds contained in SGD were measured by high-performance liquid chromatography. A rat model of IBS was induced by chronic water avoidance stress (WAS). The number of fecal pellets was counted after WAS and the pain pressure threshold was measured by colorectal distension. Morphological changes in colonic mucosa were detected by hematoxylin-eosin staining. The contents of tumor necrosis factor (TNF)-α in colonic tissue and calcitonin-gene-related peptide (CGRP) in serum were measured by ELISA. The protein expression of serotonin [5-hydroxytryptamide (5-HT)], serotonin transporter (SERT), chromogranin A (CgA) and CGRP in colon tissue was measured by immunohistochemistry.

RESULTS: SGD inhibited colonic motility dysfunction and VHL in rats with IBS. Blockers of transient receptor potential (TRP) vanilloid 1 (TRPV1) (Ruthenium Red) and TRP ankyrin-1 (TRPA1) (HC-030031) and activator of protease-activated receptor (PAR)4 increased the pain pressure threshold, whereas activators of PAR2 and TRPV4 decreased the pain pressure threshold in rats with IBS. The effect of SGD on pain pressure threshold in these rats was abolished by activators of TRPV1 (capsaicin), TRPV4 (RN1747), TRPA1 (Polygodial) and PAR2 (AC55541). In addition, CGRP levels in serum and colonic tissue were both increased in these rats. TNF-α level in colonic tissue was also significantly upregulated. However, the levels of 5-HT, SERT and CgA in colonic tissue were decreased. All these pathological changes in rats with IBS were attenuated by SGD.

CONCLUSION: SGD alleviated VHL and attenuated colon motility in IBS, partly by regulating TRPV1, TRPV4, TRPA1, PAR2, 5-HT, CgA and SERT, and reducing CGRP and TNF-α level.

Keywords: Shugan decoction, Visceral hyperalgesia, Serotonin, Transient receptor potential, Protease-activated receptor, Serotonin transporter, Calcitonin-gene-related peptide, Tumor necrosis factor-α

Core tip: The present study demonstrated that Shugan decoction alleviated visceral hyperalgesia and attenuated colon motility in a rat model of irritable bowel syndrome, partly by regulating the expression of transient receptor potential (TRP) vanilloid 1, TRP vanilloid 4, TRP ankyrin-1 and protease-activated receptor 2, serotonin, chromogranin A and serotonin transporter, and reducing the levels of calcitonin-gene-related peptide and tumor necrosis factor-α.