scholarly journals Shaoyao-Gancao Decoction Relieves Visceral Hyperalgesia in TNBS-Induced Postinflammatory Irritable Bowel Syndrome via Inactivating Transient Receptor Potential Vanilloid Type 1 and Reducing Serotonin Synthesis

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Yun-Yun Shao ◽  
Yi-Ting Guo ◽  
Jian-ping Gao ◽  
Jun-Jin Liu ◽  
Zhuang-Peng Chang ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Cell Count ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Low Grade ◽  
Visceral Hyperalgesia ◽  
Transient Receptor ◽  
Irritable Bowel ◽  
In Cells

Postinflammatory irritable bowel syndrome (PI-IBS) is a common functional gastrointestinal disorder, which is characterized by abdominal pain, low-grade inflammation, and visceral hypersensitivity. Shaoyao-Gancao decoction (SGD) has been used to improve the clinical symptoms of abdominal spasmodic pain accompanying acute gastroenteritis, but the underlying therapeutic mechanism has not been fully elucidated. In the present study, a rat model of PI-IBS was established via rectal administration of TNBS. Rats were scored daily for 28 days using disease activity index (DAI). Abdominal withdrawal reflex (AWR) was used to measure the pain threshold. After SGD (6.25, 12.5, and 25 g/kg/d) treatment for 14 days, rat colonic tissue was collected for histopathological grading, enterochromaffin (EC) cell count, and 5-HT content measurement. RT-qPCR and western blot analyses were employed to detect the gene and protein level of tryptophan hydroxylase (TPH), serotonin reuptake transporter (SERT), and transient receptor potential vanilloid 1 (TRPV1). To further validate the effect of SGD on TRPV1, another experiment was performed in cells. The results revealed that visceral hyperalgesia, reflected by increased DAI, AWR, pathological injury score, 5-HT content, and EC cell count in PI-IBS rats, was significantly ameliorated by SGD. In cells, SGD markedly inhibited the expression and function of TRPV1. Moreover, the expression levels of TPH were also repressed by SGD. The findings of the present study indicated that the therapeutic effect of SGD on visceral hyperalgesia may be closely associated with the regulatory role of TRPV1 and 5-HT signaling pathways.

scholarly journals Essential Role of Mast Cells in the Visceral Hyperalgesia Induced byT. spiralisInfection and Stress in Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Chang-Qing Yang ◽  
Yan-Yu Wei ◽  
Chan-Juan Zhong ◽  
Li-Ping Duan
Keyword(s):  
Mast Cells ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Pcr Analysis ◽  
Signal Pathways ◽  
Transient Receptor Potential Vanilloid ◽  
Visceral Hyperalgesia ◽  
Cold Restraint Stress ◽  
Transient Receptor ◽  
Extracellular Regulated Kinase

Mast cells (MCs) deficient rats (Ws/Ws) were used to investigate the roles of MCs in visceral hyperalgesia. Ws/Ws and wild control (+/+) rats were exposed toT. spiralisor submitted to acute cold restraint stress (ACRS). Levels of proteinase-activated receptor 2 (PAR2) and nerve growth factor (NGF) were determined by immunoblots and RT-PCR analysis, and the putative signal pathways including phosphorylated extracellular-regulated kinase (pERK1/2) and transient receptor potential vanilloid receptor 1 (TRPV1) were further identified. Visceral hyperalgesia triggered by ACRS was observed only in+/+rats. The increased expression of PAR2 and NGF was observed only in+/+rats induced byT. spiralisand ACRS. The activation of pERK1/2 induced by ACRS occurred only in+/+rats. However, a significant increase of TRPV1 induced byT. spiralisand ACRS was observed only in+/+rats. The activation of PAR2 and NGF via both TRPV1 and pERK1/2 signal pathway is dependent on MCs in ACRS-induced visceral hyperalgesia rats.

scholarly journals TRPV1 Antagonists as Novel Anti-Diabetic Agents: Regulation of Oral Glucose Tolerance and Insulin Secretion Through Reduction of Low-Grade Inflammation?

2019 ◽  
Vol 7 (8) ◽  
pp. 82 ◽  
Author(s):  
Dorte X. Gram ◽  
Josefine Fribo ◽  
Istvan Nagy ◽  
Carsten Gotfredsen ◽  
Ana Charrua ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Oral Glucose ◽  
Transient Receptor Potential Vanilloid ◽  
Low Grade ◽  
Oral Glucose Tolerance ◽  
Transient Receptor ◽  
Low Grade Inflammation

With a global prevalence among adults over 18 years of age approaching 9%, Type 2 diabetes mellitus (T2DM) has reached pandemic proportions and represents a major unmet medical need. To date, no disease modifying treatment is available for T2DM patients. Accumulating evidence suggest that the sensory nervous system is involved in the progression of T2DM by maintaining low-grade inflammation via the vanilloid (capsaicin) receptor, Transient Receptor Potential Vanilloid-1 (TRPV1). In this study, we tested the hypothesis that TRPV1 is directly involved in glucose homeostasis in rodents. TRPV1 receptor knockout mice (Trpv1−/−) and their wild-type littermates were kept on high-fat diet for 15 weeks. Moreover, Zucker obese rats were given the small molecule TRPV1 antagonist, N-(4-Tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl)tetrahydropyrazine-1(2H)-carbox-amide (BCTC), per os twice-a-day or vehicle for eight days. Oral glucose tolerance and glucose-stimulated insulin secretion was improved by both genetic inactivation (Trpv1−/− mice) and pharmacological blockade (BCTC) of TRPV1. In the obese rat, the improved glucose tolerance was accompanied by a reduction in inflammatory markers in the mesenteric fat, suggesting that blockade of low-grade inflammation contributes to the positive effect of TRPV1 antagonism on glucose metabolism. We propose that TRPV1 could be a promising therapeutic target in T2DM by improving glucose intolerance and correcting dysfunctional insulin secretion.

Sign in / Sign up

Export Citation Format

Share Document