Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 7, 2019; 25(29): 3956-3971
Published online Aug 7, 2019. doi: 10.3748/wjg.v25.i29.3956
Berberine prevents stress-induced gut inflammation and visceral hypersensitivity and reduces intestinal motility in rats
Zhi-Chao Yu, Yong-Xin Cen, Ben-Hua Wu, Cheng Wei, Feng Xiong, De-Feng Li, Ting-Ting Liu, Ming-Han Luo, Li-Liangzi Guo, Ying-Xue Li, Li-Sheng Wang, Jian-Yao Wang, Jun Yao
Zhi-Chao Yu, Ben-Hua Wu, Cheng Wei, Feng Xiong, De-Feng Li, Ting-Ting Liu, Ming-Han Luo, Li-Liangzi Guo, Ying-Xue Li, Li-Sheng Wang, Jun Yao, Department of Gastroenterology, Jinan University of Second Clinical Medical Sciences, Shenzhen Municipal People’s Hospital, Shenzhen 518020, Guangdong Province, China
Yong-Xin Cen, Department of Gastroenterology, Foshan Gaoming Affiliated Hospital of Guangdong Medical University, Foshan 528500, Guangdong Province, China
Jian-Yao Wang, Department of General Surgery, Shenzhen Children’s Hospital, Shenzhen 518026, Guangdong Province, China
Author contributions: Yu ZC designed and wrote the manuscript; Cen YX and Wu BH reviewed the manuscript for its intellectual content and revised the entire work; Wei C, Xiong F, Li DF, Liu TT, Luo MH, Guo LL, and Li YX performed the histological assessments and evaluations; Wang LS, Wang JY, and Yao J reviewed the manuscript for its intellectual content; all authors have read and approved the final manuscript.
Supported by: the National Natural Science Foundation of China, No. 81800489; Shenzhen Health and Family Planning System Research Project, No. SZXJ2017030; and Technical Research and Development Project of Shenzhen, Nos. JCYJ20170307100538697 and JCYJ20170307100911479.
Institutional review board statement: This study was reviewed and approved by the Institutional Review Board of Shenzhen Municipal People’s Hospital.
Institutional animal care and use committee statement: This study was reviewed and approved by the Animal Ethical and Welfare Committee of Shenzhen University on January 12, 2016.
Conflict-of-interest statement: The authors of this manuscript have no conflicts of interest to disclose.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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/
Corresponding author: Jun Yao, MD, PhD, Doctor, Department of Gastroenterology, Jinan University of Second Clinical Medical Sciences, Shenzhen Municipal People’s Hospital, 1017 East Gate Road, Shenzhen 518020, Guangdong Province, China. yj_1108@126.com
Telephone: +86-755-25533497 Fax: +86-755-25533497
Received: February 27, 2019
Peer-review started: February 27, 2019
First decision: April 11, 2019
Revised: June 26, 2019
Accepted: July 5, 2019
Article in press: July 5, 2019
Published online: August 7, 2019
Abstract
BACKGROUND

Irritable bowel syndrome (IBS) is a common chronic non-organic disease of the digestive system. Berberine (BBR) has been used to treat patients with IBS, but the underlying therapeutic mechanism is little understood. We believe that BBR achieves its therapeutic effect on IBS by preventing stress intestinal inflammation and visceral hypersensitivity and reducing bowel motility.

AIM

To test the hypothesis that BBR achieves its therapeutic effect on IBS by preventing subclinical inflammation of the intestinal mucosa and reducing visceral hypersensitivity and intestinal motility.

METHODS

IBS was induced in rats via water avoidance stress (WAS). qRT-PCR and histological analyses were used to evaluate the levels of cytokines and mucosal inflammation, respectively. Modified ELISA and qRT-PCR were used to evaluate the nuclear factor kappa-B (NF-κB) signal transduction pathway. Colorectal distention test, gastrointestinal transit measurement, Western blot, and qRT-PCR were used to analyze visceral sensitivity, intestinal motility, the expression of C-kit (marker of Cajal mesenchymal cells), and the expression of brain derived neurotrophic factor (BDNF) and its receptor TrkB.

RESULTS

WAS led to mucosal inflammation, visceral hyperalgesia, and high intestinal motility. Oral administration of BBR inhibited the NF-κB signal transduction pathway, reduced the expression of pro-inflammatory cytokines [interleukin (IL)-1β, IL-6, interferon-γ, and tumor necrosis factor-α], promoted the expression of anti-inflammatory cytokines (IL-10 and transforming growth factor-β), and improved the terminal ileum tissue inflammation. BBR inhibited the expression of BDNF, TrkB, and C-kit in IBS rats, leading to the reduction of intestinal motility and visceral hypersensitivity. The therapeutic effect of BBR at a high dose (100 mg/kg) was superior to than that of the low-dose (25 mg/kg) group.

CONCLUSION

BBR reduces intestinal mucosal inflammation by inhibiting the intestinal NF-κB signal pathway in the IBS rats. BBR reduces the expression of BDNF, its receptor TrkB, and C-kit. BBR also reduces intestinal motility and visceral sensitivity to achieve its therapeutic effect on IBS.

Keywords: Irritable bowel syndrome, Visceral hypersensitivity, Berberine, Rifampicin, Nuclear factor kappa-B, Brain-derived neurotrophic factor, Cajal mesenchymal cells, C-kit

Core tip: Irritable bowel syndrome (IBS) is a common chronic non-organic disease of the digestive system and the pathophysiology of IBS is still not completely understood. Berberine has been used to treat patients with IBS, but little is known regarding to its therapeutic mechanism. This study aimed to determine the therapeutic effect of berberine on IBS and its underlying mechanisms. The results demonstrated that the therapeutic efficacy of berberine was dose-dependent and may be associated with the inhibition of the intestinal nuclear factor kappa-B signal pathway, the expression of brain derived neurotrophic factor and its receptor TrkB, and the expression of C-kit to reduce intestinal motility and visceral sensitivity.