Published online Aug 7, 2019. doi: 10.3748/wjg.v25.i29.3956
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
Irritable bowel syndrome (IBS) is a common chronic non-organic disease of the digestive system. Rifaximin has been used in clinical treatment of patients with IBS and has achieved good efficacy. However, rifaximin is expensive, and long-term oral administration may lead to cross-resistance to rifabutin and rifampicin. A large number of basic and clinical studies have also shown the efficacy of berberine in the treatment of IBS.
Many studies have demonstrated that the pathogenesis of IBS may be related to the disorder of brain-gut axis, visceral hypersensitivity, intestinal immune abnormality, intestinal motility change, increased intestinal mucosal permeability, and intestinal flora disorder. The treatment mechanism of berberine for IBS is still unclear. In this study, we tried to investigate the effect of berberine on intestinal inflammation, intestinal motility, and intestinal sensitivity in rats with IBS and explore the therapeutic mechanism of berberine for IBS.
The purpose of this study was to investigate the effect of berberine on the NF-κB signaling pathway in rats with IBS, which may improve intestinal inflammation in rats with IBS. And we studied the influence of berberine on the expression levels of brain-derived neurotrophic factor (BDNF) and C-kit in the intestinal tract of rats, which may affect the intestinal motility and visceral sensitivity of rats.
Water avoidance stress (WAS) was used to establish an IBS rat model, and the rats were divided into a control group, a WAS group, a rifaximin group, a 25 mg/kg BBR group, and a 100 mg/kg BBR group. We evaluated the histopathological changes of the terminal ileum in rats by hematoxylin and eosin (HE) staining. We measured the expression levels of NF-Κb (P65) DNA binding protein in the terminal ileum tissues of rats of each group by modified ELISA and Western blot. The mRNA expression levels of IL-1β, IL-6, IFN-γ, TNF-α, IL-10, and TGF-β were determined by qRT-PCR. ELISA was used to detect the inflammatory cytokines. Intestinal motility of rats in each group was detected by total gastrointestinal and small intestinal transit functions. The mRNA expression levels of BDNF and its receptor TrkB were detected by qRT-PCR. Western blot was used to detect the expression level of TrkB protein in the terminal ileum tissues in each group of rats. The mRNA expression levels of C-kit in ileum terminal tissues of rats in each group were detected by qRT-PCR. The expression level of C-kit protein in ileum terminal tissues of each group of rats was detected by Western blot.
We successfully applied the WAS model to induce visceral hypersensitivity in rats, changes in intestinal inflammation, and intestinal motility, which are consistent with the characteristics of IBS. Berberine can effectively improve the inflammation of in terminal tissues. Berberine can inhibit the activated NF-κB signal pathway in the intestinal tract of IBS rats, significantly reduce the expression of inflammatory IL-1β, IL-6, IFN-γ, and TNF-α in the terminal ileum tissues of IBS rats, and significantly increase the expression levels of anti-inflammatory cytokines IL-10 and TGF-β. Berberine can effectively regulate the intestinal motility of IBS rats and inhibit the expression of BDNF and its receptor TrkB as well as C-kit in ileum terminal tissues of IBS rats. The treatment effect of large dose (100 mg/kg) berberine on IBS rats was significantly better than that of small dose (25 mg/kg) berberine.
Berberine can inhibit the mucosal inflammation of the intestinal tract by inhibiting the intestinal NF-κB signal pathway in IBS rats. Berberine reduces the expression of BDNF and its receptor TrkB as well as C-kit to reduce intestinal motility and visceral sensitivity and produce a therapeutic effect on IBS. The therapeutic effect of 100 mg/kg berberine is superior to that of 25 mg/kg berberine.
This study confirms the exact therapeutic effect of berberine on IBS at the level of animal experiments, discusses the possible mechanism of its therapeutic effect, and provides a theoretical basis for the clinical application of berberine in the treatment of IBS. However, the optimal dosage of berberine in the clinical treatment of IBS still needs further pharmacological and toxicological studies