title: The effect of curcumin on the brain-gut axis in rat model of irritable bowel syndrome: involvement of 5-HT-dependent signaling.
abstract: Irritable bowel syndrome (IBS) is induced by dysfunction of central nervous and peripheral intestinal systems, which affects an estimated 10-15% population worldwide annually. Stress-related psychiatric disorders including depression and anxiety are often comorbid with gastrointestinal function disorder, such as IBS. However, the mechanism of IBS still remains unknown. Curcumin is a biologically active phytochemical presents in turmeric and has pharmacological actions that benefit patients with depression and anxiety. Our study found that IBS rats showed depression- and anxiety-like behaviors associated with decreased 5-HT (serotonin), BDNF (Brain-derived neurotrophic factor) and pCREB (phosphorylation of cAMP response element-binding protein) expression in the hippocampus after chronic acute combining stress (CAS). However, these decreased parameters were obviously increased in the colonic after CAS. Curcumin (40 mg/kg) reduced the immobility time of forced swimming and the number of buried marbles in behavioral tests of CAS rats. Curcumin also decreased the number of fecal output and abdominal withdrawal reflex (AWR) scores in response to graded distention. Moreover, curcumin increased serotonin, BDNF and pCREB levels in the hippocampus, but they were decreased in the colonic of CAS rats. 5-HT(1A) receptor antagonist NAN-190 reversed the effects of curcumin on behaviors and the changes of intestine, pCREB and BDNF expression, which are related to IBS. These results suggested that curcumin exerts the effects on IBS through regulating neurotransmitters, BDNF and CREB signaling both in the brain and peripheral intestinal system.
authors.affiliation: Department of Gastroenterology, Wenzhou No.3 Clinical Institute of Wenzhou Medical University, Wenzhou people's hospital, Wenzhou, Zhejiang Province, 325000, China.
authors.forename: Yingcong
authors.initials: Y
authors.lastname: Yu
authors.forename: Shujuan
authors.initials: S
authors.lastname: Wu
authors.forename: Jianxin
authors.initials: J
authors.lastname: Li
authors.forename: Renye
authors.initials: R
authors.lastname: Wang
authors.forename: Xupei
authors.initials: X
authors.lastname: Xie
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Yu
authors.forename: Jianchun
authors.initials: J
authors.lastname: Pan
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.forename: Liang
authors.initials: L
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D003106:Colon / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use*; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis; D003672:Defecation; D003975:Diazepam / Q000494:pharmacology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D017615:Enteric Nervous System / Q000503:physiopathology*; D005769:Gastrointestinal Motility / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology*; D007099:Imipramine / Q000494:pharmacology; D043183:Irritable Bowel Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D010766:Phosphorylation; D005082:Physical Exertion; D010879:Piperazines / Q000494:pharmacology; D011312:Pressure / Q000009:adverse effects; D011499:Protein Processing, Post-Translational; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000096:biosynthesis / Q000502:physiology*; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology; D015398:Signal Transduction; D013312:Stress, Physiological / Q000502:physiology; D013315:Stress, Psychological / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D010879:Piperazines; D058829:Serotonin 5-HT1 Receptor Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; D012701:Serotonin; D003474:Curcumin; D007099:Imipramine; D003975:Diazepam