Berberine prevents stress-induced gut inflammation and visceral hypersensitivity and reduces intestinal motility in rats

World J Gastroenterol. 2019 Aug 7;25(29):3956-3971. doi: 10.3748/wjg.v25.i29.3956.


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

MeSH terms

  • Animals
  • Berberine / pharmacology*
  • Berberine / therapeutic use
  • Cytokines / immunology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Enteric Nervous System / drug effects*
  • Enteric Nervous System / physiopathology
  • Gastrointestinal Motility / drug effects
  • Gastrointestinal Motility / immunology
  • Humans
  • Hyperalgesia / drug therapy*
  • Hyperalgesia / physiopathology
  • Hyperalgesia / psychology
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / innervation
  • Irritable Bowel Syndrome / drug therapy*
  • Irritable Bowel Syndrome / immunology
  • Irritable Bowel Syndrome / psychology
  • Male
  • Rats
  • Stress, Psychological / complications*
  • Stress, Psychological / psychology
  • Treatment Outcome


  • Cytokines
  • Berberine