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The effect of curcumin on the brain-gut axis in rat model of irritable bowel syndrome: involvement of 5-HT-dependent signaling.

Metabolic brain disease (2014-05-09)
Yingcong Yu, Shujuan Wu, Jianxin Li, Renye Wang, Xupei Xie, Xuefeng Yu, Jianchun Pan, Ying Xu, Liang Zheng
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Curcumin, from Curcuma longa (Turmeric), powder
Sigma-Aldrich
Hydrobromic acid, ACS reagent, 48%
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Curcumin, ≥94% (curcuminoid content), ≥80% (Curcumin)
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Hydrobromic acid, reagent grade, 48%
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Hydrogen bromide solution, 33 wt. % in acetic acid
Supelco
Curcumin, analytical standard
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Hydrobromic acid solution, 33 wt. % in acetic acid
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Adenosine 3′,5′-cyclic monophosphate, ≥98.5% (HPLC), powder
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Hydrobromic acid, 48 wt. % in H2O, ≥99.99%
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Imipramine hydrochloride, ≥99% (TLC)
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Serotonin creatinine sulfate monohydrate, powder
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Curcumin, matrix substance for MALDI-MS, ≥99.5% (HPLC)
USP
Curcumin, United States Pharmacopeia (USP) Reference Standard
Curcumin, primary reference standard
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Adenosine 3′,5′-cyclic monophosphate tris salt, ≥97% (HPLC), powder
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Imipramine hydrochloride, BioXtra, ≥99% (TLC)
USP
Imipramine hydrochloride, United States Pharmacopeia (USP) Reference Standard
Imipramine hydrochloride, European Pharmacopoeia (EP) Reference Standard
Imipramine for system suitability, European Pharmacopoeia (EP) Reference Standard
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Serotonin hydrogen maleate, powder