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.

The Role of Visceral Hypersensitivity in Irritable Bowel Syndrome: Pharmacological Targets and Novel Treatments

“…The 5-HT1A receptor is suggested to be involved in the curcumin mechanism of action for the management of VH in rats with IBS. 125 Another in vivo study showed a remarkable decrease by curcumin in visceromotor response to colorectal distension in rats. 126 Ex vivo assessments on TNBS-treated jejunum confirmed the peripheral effect of curcumin on mesenteric afferent nerves.…”

Curcumin in antidepressant treatments: An overview of potential mechanisms, pre‐clinical/clinical trials and ongoing challenges

“…70 Recently, a study has found that curcumin could increase the expression levels of BDNF, 5-HT as well as pCREB in the hippocampus of irritable bowel syndrome (IBS) rats with anxiety and depression behaviours. 75 Another study suggested that curcumin could enhance post-synaptic electrical reactivity in neural circuits by upregulating the BDNF level and downregulating the inflammatory factors in the brain, resulting in the efficient antidepressant outcomes. 76…”

Effects of curcumin consumption on human chronic diseases: A narrative review of the most recent clinical data

“…Additionally, concerning curcumin's antiarthritic effect, it has been suggested that curcumin can modulate signaling pathways in the gut, inducing somatostatin secretion from endocrine cells in small intestine (Y. Yang, Wu, et al, ). Moreover, it has been proposed that curcumin may exert an effect on the gut–brain axis, regulating neurotransmitters that signal in the gut and the brain in a rat irritable bowel syndrome model (Yu, Wu, et al, ). Thus, curcumin, despite its low bioavailability, has targets in the gut, which affect the rest of the body.…”