The Effect of Curcumin on the Brain-gut Axis in Rat Model of Irritable Bowel Syndrome: Involvement of 5-HT-dependent Signaling

Overview

Journal Metab Brain Dis

Publisher Springer

Specialties Endocrinology
Neurology

Date 2014 May 9

PMID 24807589

Citations 31

Authors

Yingcong Yu

Shujuan Wu

Jianxin Li

Renye Wang

Xupei Xie

Xuefeng Yu

Jianchun Pan

Ying Xu

Liang Zheng

Affiliations

Soon will be listed here.

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.

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References

Bian Z, Zhang M, Han Q, Xu H, Sung J . Analgesic effects of JCM-16021 on neonatal maternal separation-induced visceral pain in rats. World J Gastroenterol. 2010; 16(7):837-45. PMC: 2825330. DOI: 10.3748/wjg.v16.i7.837. View

Barone F, Deegan J, Price W, Fowler P, Fondacaro J, Ormsbee 3rd H . Cold-restraint stress increases rat fecal pellet output and colonic transit. Am J Physiol. 1990; 258(3 Pt 1):G329-37. DOI: 10.1152/ajpgi.1990.258.3.G329. View

Ness T, Gebhart G . Colorectal distension as a noxious visceral stimulus: physiologic and pharmacologic characterization of pseudaffective reflexes in the rat. Brain Res. 1988; 450(1-2):153-69. DOI: 10.1016/0006-8993(88)91555-7. View

Clouse R . Antidepressants for irritable bowel syndrome. Gut. 2003; 52(4):598-9. PMC: 1773590. DOI: 10.1136/gut.52.4.598. View

Bambico F, Nguyen N, Gobbi G . Decline in serotonergic firing activity and desensitization of 5-HT1A autoreceptors after chronic unpredictable stress. Eur Neuropsychopharmacol. 2009; 19(3):215-28. DOI: 10.1016/j.euroneuro.2008.11.005. View

Johansson M, Norrgard O, Forsgren S . Study of expression patterns and levels of neurotrophins and neurotrophin receptors in ulcerative colitis. Inflamm Bowel Dis. 2007; 13(4):398-409. DOI: 10.1002/ibd.20072. View

Friedrich M, Grady S, Wall G . Effects of antidepressants in patients with irritable bowel syndrome and comorbid depression. Clin Ther. 2010; 32(7):1221-33. DOI: 10.1016/j.clinthera.2010.07.002. View

Dunlop S, Coleman N, Blackshaw E, Perkins A, Singh G, Marsden C . Abnormalities of 5-hydroxytryptamine metabolism in irritable bowel syndrome. Clin Gastroenterol Hepatol. 2005; 3(4):349-57. DOI: 10.1016/s1542-3565(04)00726-8. View

Drossman D, Camilleri M, Mayer E, Whitehead W . AGA technical review on irritable bowel syndrome. Gastroenterology. 2002; 123(6):2108-31. DOI: 10.1053/gast.2002.37095. View

10.

Xu Y, Ku B, Yao H, Lin Y, Ma X, Zhang Y . The effects of curcumin on depressive-like behaviors in mice. Eur J Pharmacol. 2005; 518(1):40-6. DOI: 10.1016/j.ejphar.2005.06.002. View

11.

Siuciak J, Altar C, Wiegand S, Lindsay R . Antinociceptive effect of brain-derived neurotrophic factor and neurotrophin-3. Brain Res. 1994; 633(1-2):326-30. DOI: 10.1016/0006-8993(94)91556-3. View

12.

Talley N, Owen B, Boyce P, Paterson K . Psychological treatments for irritable bowel syndrome: a critique of controlled treatment trials. Am J Gastroenterol. 1996; 91(2):277-83. View

13.

Abdul-Baki H, El Hajj I, Elzahabi L, Azar C, Aoun E, Skoury A . A randomized controlled trial of imipramine in patients with irritable bowel syndrome. World J Gastroenterol. 2009; 15(29):3636-42. PMC: 2721237. DOI: 10.3748/wjg.15.3636. View

14.

Schneider T, Popik P . Attenuation of estrous cycle-dependent marble burying in female rats by acute treatment with progesterone and antidepressants. Psychoneuroendocrinology. 2007; 32(6):651-9. DOI: 10.1016/j.psyneuen.2007.04.003. View

15.

Njunge K, Handley S . Effects of 5-HT uptake inhibitors, agonists and antagonists on the burying of harmless objects by mice; a putative test for anxiolytic agents. Br J Pharmacol. 1991; 104(1):105-12. PMC: 1908295. DOI: 10.1111/j.1476-5381.1991.tb12392.x. View

16.

Xu Y, Ku B, Cui L, Li X, Barish P, Foster T . Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and brain-derived neurotrophic factor expression in chronically stressed rats. Brain Res. 2007; 1162:9-18. DOI: 10.1016/j.brainres.2007.05.071. View

17.

Xu Y, Ku B, Tie L, Yao H, Jiang W, Ma X . Curcumin reverses the effects of chronic stress on behavior, the HPA axis, BDNF expression and phosphorylation of CREB. Brain Res. 2006; 1122(1):56-64. DOI: 10.1016/j.brainres.2006.09.009. View

18.

Yeo A, Boyd P, Lumsden S, Saunders T, Handley A, Stubbins M . Association between a functional polymorphism in the serotonin transporter gene and diarrhoea predominant irritable bowel syndrome in women. Gut. 2004; 53(10):1452-8. PMC: 1774243. DOI: 10.1136/gut.2003.035451. View

19.

Yu Y, Zuo X, Zhao Q, Chen F, Yang J, Dong Y . Brain-derived neurotrophic factor contributes to abdominal pain in irritable bowel syndrome. Gut. 2011; 61(5):685-94. DOI: 10.1136/gutjnl-2011-300265. View

20.

Lydiard R . Irritable bowel syndrome, anxiety, and depression: what are the links?. J Clin Psychiatry. 2002; 62 Suppl 8:38-45; discussion 46-7. View