Published online Feb 14, 2018. doi: 10.3748/wjg.v24.i6.693
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
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.
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.
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.
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
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
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.
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.