Basic Study
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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
Abstract
AIM

To elucidate the mechanism of patchouli alcohol (PA) in treatment of rat models of diarrhea-predominant irritable bowel syndrome (IBS-D).

METHODS

We studied the effects of PA on colonic spontaneous motility using its cumulative log concentration (3 × 10−7 mol/L to 1 × 10−4 mol/L). We then determined the responses of the proximal and distal colon segments of rats to the following stimuli: (1) carbachol (1 × 10−9 mol/L to 1 × 10−5 mol/L); (2) neurotransmitter antagonists including Nω-nitro-L-arginine methyl ester hydrochloride (10 μmol/L) and (1R*, 2S*)-4-[2-Iodo-6-(methylamino)-9H-purin-9-yl]-2-(phosphonooxy)bicyclo[3.1.0]hexane-1-methanol dihydrogen phosphate ester tetraammonium salt (1 μmol/L); (3) agonist α,β-methyleneadenosine 5′-triphosphate trisodium salt (100 μmol/L); and (4) single KCl doses (120 mmol/L). The effects of blockers against antagonist responses were also assessed by pretreatment with PA (100 μmol/L) for 1 min. Electrical-field stimulation (40 V, 2-30 Hz, 0.5 ms pulse duration, and 10 s) was performed to observe nonadrenergic, noncholinergic neurotransmitter release in IBS-D rat colon. The ATP level of Kreb’s solution was also determined.

RESULTS

PA exerted a concentration-dependent inhibitory effect on the spontaneous contraction of the colonic longitudinal smooth muscle, and the half maximal effective concentration (EC50) was 41.9 μmol/L. In comparison with the KCl-treated IBS-D group, the contractile response (mg contractions) in the PA + KCl-treated IBS-D group (11.87 ± 3.34) was significantly decreased in the peak tension (P < 0.01). Compared with CCh-treated IBS-D rat colon, the cholinergic contractile response of IBS-D rat colonic smooth muscle (EC50 = 0.94 μmol/L) was significantly decreased by PA (EC50 = 37.43 μmol/L) (P < 0.05). Lack of nitrergic neurotransmitter release in stress-induced IBS-D rats showed contraction effects on colonic smooth muscle. Pretreatment with PA resulted in inhibitory effect on L-NAME-induced (10 μmol/L) contraction (P < 0.05). ATP might not be the main neurotransmitter involved in inhibitory effects of PA in the colonic relaxation of stress-induced IBS-D rats.

CONCLUSION

PA application may serve as a new therapeutic approach for IBS-D.

Keywords: Patchouli alcohol; Colonic longitudinal smooth muscles; Diarrhea-predominant irritable bowel syndrome; Enteric nervous system; Cholinergic nerves; Non-adrenergic non-cholinergic; Potassium channel

Core tip: We reported the results from an isolated colonic smooth muscle experiment in a chronic wrap-restraint stress-induced rat model of diarrhea-predominant irritable bowel syndrome (IBS-D). The model enabled us to study the possible mechanisms underlying IBS-D and the inhibitory effects of patchouli alcohol (PA) on an isolated IBS-D rat colon. This study demonstrated for the first time that the PA was involved in cholinergic and nonadrenergic, noncholinergic neurotransmitter regulation in the enteric nervous system (ENS) in vitro. PA acts as a neurotransmitter agent in ENS. The results suggest that PA is a new treatment option for IBS-D.