PMID- 31413530 OWN - NLM STAT- MEDLINE DCOM- 20200214 LR - 20200225 IS - 2219-2840 (Electronic) IS - 1007-9327 (Print) IS - 1007-9327 (Linking) VI - 25 IP - 29 DP - 2019 Aug 7 TI - Berberine prevents stress-induced gut inflammation and visceral hypersensitivity and reduces intestinal motility in rats. PG - 3956-3971 LID - 10.3748/wjg.v25.i29.3956 [doi] AB - 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-kappaB) 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-kappaB signal transduction pathway, reduced the expression of pro-inflammatory cytokines [interleukin (IL)-1beta, IL-6, interferon-gamma, and tumor necrosis factor-alpha], promoted the expression of anti-inflammatory cytokines (IL-10 and transforming growth factor-beta), 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-kappaB 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. FAU - Yu, Zhi-Chao AU - Yu ZC AD - Department of Gastroenterology, Jinan University of Second Clinical Medical Sciences, Shenzhen Municipal People's Hospital, Shenzhen 518020, Guangdong Province, China. FAU - Cen, Yong-Xin AU - Cen YX AD - Department of Gastroenterology, Foshan Gaoming Affiliated Hospital of Guangdong Medical University, Foshan 528500, Guangdong Province, China. FAU - Wu, Ben-Hua AU - Wu BH AD - Department of Gastroenterology, Jinan University of Second Clinical Medical Sciences, Shenzhen Municipal People's Hospital, Shenzhen 518020, Guangdong Province, China. FAU - Wei, Cheng AU - Wei C AD - Department of Gastroenterology, Jinan University of Second Clinical Medical Sciences, Shenzhen Municipal People's Hospital, Shenzhen 518020, Guangdong Province, China. FAU - Xiong, Feng AU - Xiong F AD - Department of Gastroenterology, Jinan University of Second Clinical Medical Sciences, Shenzhen Municipal People's Hospital, Shenzhen 518020, Guangdong Province, China. FAU - Li, De-Feng AU - Li DF AD - Department of Gastroenterology, Jinan University of Second Clinical Medical Sciences, Shenzhen Municipal People's Hospital, Shenzhen 518020, Guangdong Province, China. FAU - Liu, Ting-Ting AU - Liu TT AD - Department of Gastroenterology, Jinan University of Second Clinical Medical Sciences, Shenzhen Municipal People's Hospital, Shenzhen 518020, Guangdong Province, China. FAU - Luo, Ming-Han AU - Luo MH AD - Department of Gastroenterology, Jinan University of Second Clinical Medical Sciences, Shenzhen Municipal People's Hospital, Shenzhen 518020, Guangdong Province, China. FAU - Guo, Li-Liangzi AU - Guo LL AD - Department of Gastroenterology, Jinan University of Second Clinical Medical Sciences, Shenzhen Municipal People's Hospital, Shenzhen 518020, Guangdong Province, China. FAU - Li, Ying-Xue AU - Li YX AD - Department of Gastroenterology, Jinan University of Second Clinical Medical Sciences, Shenzhen Municipal People's Hospital, Shenzhen 518020, Guangdong Province, China. FAU - Wang, Li-Sheng AU - Wang LS AD - Department of Gastroenterology, Jinan University of Second Clinical Medical Sciences, Shenzhen Municipal People's Hospital, Shenzhen 518020, Guangdong Province, China. FAU - Wang, Jian-Yao AU - Wang JY AD - Department of General Surgery, Shenzhen Children's Hospital, Shenzhen 518026, Guangdong Province, China. FAU - Yao, Jun AU - Yao J AD - Department of Gastroenterology, Jinan University of Second Clinical Medical Sciences, Shenzhen Municipal People's Hospital, Shenzhen 518020, Guangdong Province, China. yj_1108@126.com. LA - eng PT - Journal Article PL - United States TA - World J Gastroenterol JT - World journal of gastroenterology JID - 100883448 RN - 0 (Cytokines) RN - 0I8Y3P32UF (Berberine) SB - IM MH - Animals MH - Berberine/*pharmacology/therapeutic use MH - Cytokines/immunology/metabolism MH - Disease Models, Animal MH - Enteric Nervous System/*drug effects/physiopathology MH - Gastrointestinal Motility/drug effects/immunology MH - Humans MH - Hyperalgesia/*drug therapy/physiopathology/psychology MH - Intestinal Mucosa/drug effects/immunology/innervation MH - Irritable Bowel Syndrome/*drug therapy/immunology/psychology MH - Male MH - Rats MH - Stress, Psychological/*complications/psychology MH - Treatment Outcome PMC - PMC6689801 OTO - NOTNLM OT - Berberine OT - Brain-derived neurotrophic factor OT - C-kit OT - Cajal mesenchymal cells OT - Irritable bowel syndrome OT - Nuclear factor kappa-B OT - Rifampicin OT - Visceral hypersensitivity COIS- Conflict-of-interest statement: The authors of this manuscript have no conflicts of interest to disclose. EDAT- 2019/08/16 06:00 MHDA- 2020/02/15 06:00 PMCR- 2019/08/07 CRDT- 2019/08/16 06:00 PHST- 2019/02/27 00:00 [received] PHST- 2019/06/26 00:00 [revised] PHST- 2019/07/05 00:00 [accepted] PHST- 2019/08/16 06:00 [entrez] PHST- 2019/08/16 06:00 [pubmed] PHST- 2020/02/15 06:00 [medline] PHST- 2019/08/07 00:00 [pmc-release] AID - 10.3748/wjg.v25.i29.3956 [doi] PST - ppublish SO - World J Gastroenterol. 2019 Aug 7;25(29):3956-3971. doi: 10.3748/wjg.v25.i29.3956.