Journal
WORLD JOURNAL OF GASTROENTEROLOGY
Volume 21, Issue 16, Pages 4852-4863Publisher
BAISHIDENG PUBLISHING GROUP INC
DOI: 10.3748/wjg.v21.i16.4852
Keywords
Shugan decoction; Visceral hyperalgesia; Serotonin; Transient receptor potential; Protease-activated receptor; Serotonin transporter; Calcitonin-gene-related peptide; Tumor necrosis factor-alpha
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Funding
- Innovation Program of the Shanghai Municipal Education Commission [12YZ065]
- National Natural Science Foundation of China [81072786, 81473630, 81202665]
- Longhua Medical Project [D-09]
- High level Project of the University of Educational Commission of Shanghai, China [2008GSP19]
- Shanghai Leading Academic Discipline Project [J50305]
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AIM: To determine the molecular mechanisms of Shugan decoction (SGD) in the regulation of colonic motility and visceral hyperalgesia (VHL) in irritable bowel syndrome (IBS). METHODS: The chemical compounds contained in SGD were measured by high-performance liquid chromatography. A rat model of IBS was induced by chronic water avoidance stress (WAS). The number of fecal pellets was counted after WAS and the pain pressure threshold was measured by colorectal distension. Morphological changes in colonic mucosa were detected by hematoxylin-eosin staining. The contents of tumor necrosis factor (TNF)-alpha in colonic tissue and calcitonin-gene-related peptide (CGRP) in serum were measured by ELISA. The protein expression of serotonin [5-hydroxytryptamide (5-HT)], serotonin transporter (SERT), chromogranin A (CgA) and CGRP in colon tissue was measured by immunohistochemistry. RESULTS: SGD inhibited colonic motility dysfunction and VHL in rats with IBS. Blockers of transient receptor potential (TRP) vanilloid 1 (TRPV1) (Ruthenium Red) and TRP ankyrin-1 (TRPA1) (HC-030031) and activator of protease-activated receptor (PAR) 4 increased the pain pressure threshold, whereas activators of PAR2 and TRPV4 decreased the pain pressure threshold in rats with IBS. The effect of SGD on pain pressure threshold in these rats was abolished by activators of TRPV1 (capsaicin), TRPV4 (RN1747), TRPA1 (Polygodial) and PAR2 (AC55541). In addition, CGRP levels in serum and colonic tissue were both increased in these rats. TNF-alpha level in colonic tissue was also significantly upregulated. However, the levels of 5-HT, SERT and CgA in colonic tissue were decreased. All these pathological changes in rats with IBS were attenuated by SGD. CONCLUSION: SGD alleviated VHL and attenuated colon motility in IBS, partly by regulating TRPV1, TRPV4, TRPA1, PAR2, 5-HT, CgA and SERT, and reducing CGRP and TNF-alpha alpha level.
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