Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 21, 2015; 21(31): 9358-9366
Published online Aug 21, 2015. doi: 10.3748/wjg.v21.i31.9358
Mechanism of aqueous fructus aurantii immaturus extracts in neuroplexus of cathartic colons
Shi-Yi Wang, Yan-Ping Liu, Yi-Hong Fan, Lu Zhang, Li-Jun Cai, Bin Lv
Shi-Yi Wang, Yan-Ping Liu, Yi-Hong Fan, Lu Zhang, Li-Jun Cai, Bin Lv, Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
Author contributions: Wang SY and Liu YP performed the experiments, analyzed the data, and wrote the paper; Fan YH and Zhang L designed the research, revised the paper, and contributed equally to this study; Cai LJ and Lv B performed parts of the experiments and provided valuable suggestions for this study; all authors have read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 81473506; Natural Science Foundation of Zhejiang Province, No. LY13H030011; State Administration of Traditional Chinese Medicine of Zhejiang Province, No. 2013ZB050.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Zhejiang Chinese Medical University.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of Zhejiang Chinese Medical University.
Conflict-of-interest statement: All the authors declare that they have no conflicts of interest.
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: Yi-Hong Fan, PhD, Associate Professor, Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, No. 54, Youdian Road, Hangzhou 310006, Zhejiang Province, China. yhfansjr@163.com
Telephone: +86-571-87608001 Fax: +86-571-87608001
Received: March 9, 2015
Peer-review started: March 10, 2015
First decision: April 23, 2015
Revised: May 21, 2015
Accepted: June 26, 2015
Article in press: June 26, 2015
Published online: August 21, 2015
Abstract

AIM: To examine the effect of aqueous fructus aurantii immaturus (FAI) extracts on the intestinal plexus of cathartic colons.

METHODS: Cathartic colons were induced in rats with dahuang, a laxative used in traditional Chinese medicine. Once the model was established (after approximately 12 wk), rats were administered mosapride (1.54 mg/kg) or various doses of aqueous FAI extracts (1-4 g/kg) for 14 d. Transit function was assessed using an ink propulsion test. Rats were then sacrificed, and the ultramicrostructure of colonic tissue was examined using transmission electron microscopy. The expression of the 5-hydroxytryptamine receptor 4 (5-HTR4) and neurofilament-H was assessed in colon tissues using real-time PCR, Western blot, and immunohistochemistry.

RESULTS: Mosapride and high dose (4 g/kg) of aqueous FAI extracts significantly improved the bowel movement in cathartic colons compared to untreated model colons as measured by the intestinal transit rate (70.06 ± 7.25 and 72.02 ± 8.74, respectively, vs 64.12 ± 5.19; P < 0.05 for both). Compared to controls, the ultramicrostructure of cathartic colons showed signs of neural degeneration. Treatment with mosapride and aqueous FAI extracts resulted in recovery of ultrastructural pathology. Treatment with mosapride alone upregulated the gene and protein expression of 5-HTR4 compared to untreated controls (P < 0.05 for both). Treatment with aqueous FAI extracts (≥ 2 g/kg) increased 5-HTR4 mRNA levels (P < 0.05), but no change in protein level was observed by Western blot or immunohistochemistry. The mRNA and protein levels of neurofilament-H were significantly increased with mosapride and ≥ 2 g/kg aqueous FAI extracts compared to controls (P < 0.05 for all).

CONCLUSION: Aqueous FAI extracts and mosapride strengthen bowel movement in cathartic colons via increasing the expression of 5-HTR4 and neurofilament-H.

Keywords: Fructus aurantii immaturus, Aqueous extracts, Cathartic colon, 5-HTR4, Neurofilament, Myenteric plexus

Core tip: Bowel movements in cathartic colon can be strengthened with mosapride. However, recent studies show that aqueous fructus aurantii immaturus (FAI) extracts, a traditional Chinese medicine, can also strengthen bowel movement, and are widely used to treat gastrointestinal symptoms. The aim of this study was to identify the mechanism by which aqueous FAI extracts exert these effects. In a rat model of cathartic colons, treatment with mosapride and aqueous FAI extracts improved the intestinal transit rate, and increased the expression of 5-hydroxytryptamine receptor 4 and neurofilament-H.