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. 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.
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.
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.
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.
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.
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.