Berberine Improves Intestinal Motility and Visceral Pain in the Mouse Models Mimicking Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D) Symptoms in an Opioid-Receptor Dependent Manner

PLoS One. 2015 Dec 23;10(12):e0145556. doi: 10.1371/journal.pone.0145556. eCollection 2015.

Abstract

Background and aims: Berberine and its derivatives display potent analgesic, anti-inflammatory and anticancer activity. Here we aimed at characterizing the mechanism of action of berberine in the gastrointestinal (GI) tract and cortical neurons using animal models and in vitro tests.

Methods: The effect of berberine was characterized in murine models mimicking diarrhea-predominant irritable bowel syndrome (IBS-D) symptoms. Then the opioid antagonists were used to identify the receptors involved. Furthermore, the effect of berberineon opioid receptors expression was established in the mouse intestine and rat fetal cortical neurons.

Results: In mouse models, berberine prolonged GI transit and time to diarrhea in a dose-dependent manner, and significantly reduced visceral pain. In physiological conditions the effects of berberine were mediated by mu- (MOR) and delta- (DOR) opioid receptors; hypermotility, excessive secretion and nociception were reversed by berberine through MOR and DOR-dependent action. We also found that berberine increased the expression of MOR and DOR in the mouse bowel and rat fetal cortical neurons.

Conclusion: Berberine significantly improved IBS-D symptoms in animal models, possibly through mu- and delta- opioid receptors. Berberine may become a new drug candidate for the successful treatment of IBS-D in clinical conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Berberine / pharmacology*
  • Diarrhea / complications
  • Diarrhea / drug therapy*
  • Disease Models, Animal*
  • Female
  • Gastrointestinal Motility / drug effects*
  • Irritable Bowel Syndrome / complications
  • Irritable Bowel Syndrome / drug therapy*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Receptors, Opioid / genetics
  • Receptors, Opioid / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Visceral Pain / drug therapy*
  • Visceral Pain / etiology

Substances

  • RNA, Messenger
  • Receptors, Opioid
  • Berberine

Grants and funding

This work was supported by grants awarded to Dr. Chunqiu Chen and Dr. Yongyu Li from the National Science Foundation of China (No. 81170345 and No. 31571181), and by bilateral cooperation project between China and Poland from the Ministry of Science and technology (Chunqiu Chen and Jakub Fichna No.36-25, 2015).