Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2018; 24(6): 693-705
Published online Feb 14, 2018. doi: 10.3748/wjg.v24.i6.693
Inhibitory effects of patchouli alcohol on stress-induced diarrhea-predominant irritable bowel syndrome
Tian-Ran Zhou, Jing-Jing Huang, Zi-Tong Huang, Hong-Ying Cao, Bo Tan
Tian-Ran Zhou, Jing-Jing Huang, Zi-Tong Huang, Bo Tan, The Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China
Hong-Ying Cao, School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China
Author contributions: Zhou TR participated in the design of the study, performed the experiments, statistical analysis and drafted the manuscript; Tan B and Cao HY participated in the design of the research and helped to draft the manuscript; Huang JJ and Huang ZT assisted in the performance and the recording of experiments. All the authors have read and approved the submission of manuscript.
Supported by the National Natural Science Foundation of China, No. 81573715; Natural Science Foundation of Guangdong Province, China, No. 2015A030313348; and Science and Technology Program of Guangzhou, China, No. 201510010257.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Guangzhou University of Chinese Medicine, Guangzhou, China.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of Guangzhou University of Chinese Medicine (IACUC protocol number: [2017038]).
Conflict-of-interest statement: The authors declare that there is no conflict of interest exists in this study.
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: Bo Tan, MD, PhD, Associate Professor, The Research Center for Integrative Medicine, School of Fundamental Medical Sciences, Guangzhou University of Chinese Medicine, 233 Waihuan Dong Rd, Guangzhou 510006, Guangdong Province, China. tannyhy@gzucm.edu.cn
Telephone: +86-20-39358806
Received: September 14, 2017
Peer-review started: September 14, 2017
First decision: October 24, 2017
Revised: November 6, 2017
Accepted: November 28, 2017
Article in press: November 28, 2017
Published online: February 14, 2018
Processing time: 144 Days and 23.7 Hours
ARTICLE HIGHLIGHTS
Research background

Irritable bowel syndrome (IBS) is a prevalent functional bowel disorder that inflicts a significant socioeconomic burden and decreases the patient quality of life. In China, the percentage of patients with diarrhea-predominant IBS (IBS-D) is 74.1%. Therefore, the neuropsychological factors have gained much attention in the clinical and basic studies on IBS-D. However, a standard treatment algorithm has not been established for this condition. Pogostemonis Herba is used in Asian countries to treat functional gastrointestinal disorders; patchouli alcohol is the major active ingredient of Pogostemonis Herba. Previous studies have indicated that patchouli alcohol (PA) may participate in the neurotransmission regulation of the smooth muscles in the digestive system. However, no research on the pharmacological effects of PA in the neurotransmission regulation has been published.

Research motivation

This study aimed to investigate the effects of PA on the isolated IBS-D rat colon and its related mechanisms. The findings in this work can help extend the pharmacological applications of PA.

Research objectives

The main objective of this study was to test our hypothesis that the mechanism of PA in treatment of IBS-D is related to the drug regulation of the neural pathways in the enteric nervous system via its influence on the neurotransmitter release with focus on PA research. Additional in vivo and in vitro investigations on the effect of PA and the identification of the potential pharmacological target protein in PA to treat IBS-D rat colon are needed.

Research methods

In this in vitro study, the effect of PA on colonic spontaneous motility was studied using the cumulative log concentration (3 × 10−7 mol/L to 1 × 10−4 mol/L). Responses to CCh (10−9 mol/L to 10−5 mol/L) and neurotransmitter antagonists, including L-NAME (10 μmol/L), MRS 2500 (1 μmol/L), agonist α,β-methyleneadenosine 5′-triphosphate trisodium salt (100 μmol/L), and single KCl doses (120 mmol/L), were obtained from the proximal and distal colon segments of rats. Effects of blockers against the antagonistic responses by pretreatment with PA of 100 μmol/L for 1 min were also assessed. enteric nervous system (40 V, 2 Hz to 30 Hz, 0.5 ms pulse duration, and 10 s) was performed to observe the nonadrenergic, noncholinergic neurotransmitter release in the IBS-D rat colon. Moreover, the ATP level of Kreb’s solution was also determined.

Research results

In this study, PA exerted a concentration-dependent inhibitory effect on the spontaneous contraction of the colonic longitudinal smooth muscle. Pretreatment of PA could inhibit the peak tension of high extracellular concentration of the KCl-induced contraction of the IBS-D rat colon. The cholinergic contractile response in the colonic smooth muscle of IBS-D rat, which was induced by CCh, was reduced by the pretreatment of PA. Lack of nitrergic neurotransmitter, which was released in the stress-induced IBS-D rat, showed contraction effects on the colonic smooth muscle. Pretreatment of PA resulted in the relaxant effects on the L-NAME-induced contraction. Thus, ATP may not be the main neurotransmitter involved in the inhibitory effects of PA in the colonic relaxation of the stress-induced IBS-D rats. Therefore, these results indicated that PA played a role in the neurotransmission in ENS of colon, which may help extend the pharmacological applications of PA.

Research conclusions

PA exerts inhibitory effects on the IBS-D rat colon, which supports our hypothesis. In addition, related responses possibly involve cholinergic, nitrergic, and K+ channel pathways. ATP may not be the dominant pathway for participation of PA in the colonic relaxation of the stress-induced IBS-D rats. PA is a potential new candidate to effectively treat IBS-D. The findings in this study may help extend the pharmacological applications of PA. PA may be responsible for the antidiarrheal effect of Pogostemonis Herba. Additional in vivo and in vitro investigations on the effect of PA are needed, and potential pharmacological target protein for PA in treatment of IBS-D rat colon needs to be studied.

Research perspectives

Our results strongly confirmed the inhibitory effects of PA on the spontaneous, CCh-induced, and EFS-induced colonic in vitro contractions. PA acts as a neurotransmitter agent in ENS, and is thus considered to be a new treatment option for IBS-D. However, more questions will be addressed in the future studies. For instance, the pathways dominating the IBS-D colon in response to PA treatment; and the structural and functional changes in the potential target proteins under the effect of PA. The relaxation effects of PA may be related to changes in one upstream switch. Our further studies will focus on the effect of PA on the potential target proteins in IBS-D rats both in vivo and in vitro. Patch-clamp methods will be used to measure the K+ current, and immunofluorescence will be used to investigate the expression and colocalization of the target proteins. Furthermore, Western blot and qPCR will be performed to evaluate the expression of the target proteins.