title: 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.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Chunqiu
authors.initials: C
authors.lastname: Chen
authors.affiliation: Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Lu
authors.affiliation: Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Qiuhui
authors.initials: Q
authors.lastname: Pan
authors.affiliation: Department of Biochemistry, Medical University of Lodz, Lodz, Poland.
authors.forename: Jakub
authors.initials: J
authors.lastname: Fichna
authors.affiliation: Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Kesheng
authors.initials: K
authors.lastname: Wang
authors.affiliation: Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Pathophysiology, Institute of Digestive Disease, Tongji University School of Medicine, Shanghai, China.
authors.forename: Yongyu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Institute of Digestive Disease, Tongji University School of Medicine, Shanghai, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Li
authors.affiliation: Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Aihong
authors.initials: A
authors.lastname: Song
authors.affiliation: Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Zhongchen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Zhenshun
authors.initials: Z
authors.lastname: Song
authors.affiliation: Charité University Medicine, Department of General-, Visceral- and Vascular Surgery, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Kreis
mesh_terms: D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D003967:Diarrhea / Q000150:complications / Q000188:drug therapy*; D004195:Disease Models, Animal; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D043183:Irritable Bowel Syndrome / Q000150:complications / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D011957:Receptors, Opioid / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059265:Visceral Pain / Q000188:drug therapy* / Q000209:etiology
chemical_list: D012333:RNA, Messenger; D011957:Receptors, Opioid; D001599:Berberine