Resveratrol Improves Brain-Gut Axis by Regulation of 5-HT-Dependent Signaling in the Rat Model of Irritable Bowel Syndrome

Abstract

Irritable bowel syndrome (IBS) is at high risk of co-morbid depression and anxiety, which reduces patients’ quality of life and increases the burden of health care costs. However, the pathophysiological mechanisms responsible for IBS still remain unknown. This study investigated the effects of resveratrol on stress-related depression, anxiety, intestinal and visceral dysfunction in rat model of IBS. Rats received chronic acute combining stress (CACS) for 22 days exhibited depression/anxiety-like behavior, visceral hypersensitivity and altered intestinal motility, as measured by the forced swimming, marble bury, abdominal withdrawal reflex (AWR) and intestinal tract motility (ITM) tests. These abnormalities were accompanied by reduced 5-hydroxytryptamine (5-HT) level in the hippocampus and increased 5-HT expression in the gut (ileum and colon) after CACS. Chronic treatment of IBS rats with resveratrol dose-dependently normalized CACS-induced both central nervous and peripheral dysfunction, which were consistent with its differentially regulating 5-HT contents in the brain and intestine. Pretreatment with the 5-HT1A receptor antagonist NAN-190 hydrobromide (NAN-190) prevented such effects. While sub-threshold of 5-HT1A receptor agonist 8-OH-DPAT potentiated the effects of low dose of resveratrol (10 mg/kg) on CACS-related behavioral abnormalities. Furthermore, resveratrol markedly increased PKA, p-cAMP-response element binding protein (p-CREB) and brain derived neurotrophic factor (BDNF) expression in the hippocampus of IBS rats, while decreased PKA, pCREB and BDNF levels were found in the ileum and colon. These effects were prevented by NAN-190, which were consistent with the behavioral changes. The present results suggested that resveratrol improved anti-IBS-like effects on depression, anxiety, visceral hypersensitivity and intestinal motility abnormality through regulating 5-HT1A-dependent PKA-CREB-BDNF signaling in the brain-gut axis.

Transcutaneous Electrical Acupuncture Stimulation (TEAS) for gastrointestinal dysfunction in adults undergoing abdominal surgery: study protocol for a prospective randomized controlled trial

“…Clinical studies have confirmed that the contents of 5-HT in the intestinal mucosa of patients with GI dysfunction are significantly increased. Other studies have found that EA can regulate the secretion of SP, SP receptor and VIP in the IBS model colon [26] . CRF can induce repeated defecation in rats.…”

TEAS treatment improves gastrointestinal function after abdominal surgery: study protocol for a prospective randomized controlled trial

“…Clinical studies have confirmed that the contents of 5-HT in the intestinal mucosa of patients with GI dysfunction are significantly increased. Other studies have found that electroacupuncture can regulate the secretion of SP, SP receptor and VIP in the IBS model colon [33] . CRF can induce repeated defecation in rats.…”

Chang-Kang-Fang Ameliorates Experimental Diarrhea Predominant Irritable Bowel Syndrome by Regulating Gut Microbiota and Gut -Brain Axis

“…Recent studies suggested that structural and functional disruptions in BGA cause changes in perceptual and re exive responses of the nervous system and may lead to IBS-D. 5-HT is widely present in the central nervous and gastrointestinal systems in which it plays an important role in the GBA [9]. On one hand, alterations in gut motility are linked to 5-HT dysmetabolism, in which the contents of 5-HT are higher in IBS-D. And the role of 5-HT has already been exploited as a therapeutic target with the use of 5-HT 3 , a subtype of 5-HT, receptor agonists [10].…”