Oridonin Alleviates Visceral Hyperalgesia in a Rat Model of Postinflammatory Irritable Bowel Syndrome: Role of Colonic Enterochromaffin Cell and Serotonin Availability.
The aim of this present study was to investigate the effect of oridonin on visceral hyperalgesia and colonic serotonin availability in a rat model of trinitrobenzenesulfonic acid-induced postinflammatory irritable bowel syndrome (PI-IBS). Rats were randomly divided into five groups: normal control, PI-IBS model, PI-IBS+low-dose oridonin (5 mg/kg), PI-IBS+median-dose oridonin (10 mg/kg), and PI-IBS+high-dose oridonin (20 mg/kg). Rats in control and model groups were orally administered with water by gavage, whereas rats in oridonin-treated groups were orally administered with different dosages of oridonin, and drugs were given for 14 consecutive days. Compared with the control group, the pain threshold pressure was significantly reduced in PI-IBS rats. The colonic enterochromaffin (EC) cell number, serotonin content, and the protein expression of tryptophan hydroxylase (TPH) were markedly increased and the protein expression of serotonin reuptake transporter was significantly decreased in PI-IBS rats. The spleen index in PI-IBS rats was decreased, and the levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-4, and IL-13 in the colon of PI-IBS rats were also markedly decreased. Oridonin treatment dose dependently increased pain threshold pressure, and markedly decreased colon EC cell numbers, TPH expression, and serotonin content in PI-IBS rats. Oridonin treatment also significantly increased the spleen index as well as the levels of TNF-α, IFN-γ, IL-4, and IL-13 in the colon of PI-IBS rats. Results of this study demonstrate that the analgesic effect of oridonin in PI-IBS rats is associated with reduced colonic EC cell hyperplasia and 5-HT availability, the regulatory effect of oridonin on colonic cytokine production may be correlated with its effect on colonic EC cell number.
1 College of Pharmacy, Gansu University of Traditional Chinese Medicine, Lanzhou , China .
Kai-Hong
KH
Zang
2 Department of Pharmacy, First Hospital of Lanzhou University , Lanzhou, China .|3 School of Pharmaceutical, Lanzhou University , Lanzhou, China .
Yun-Yun
YY
Shao
2 Department of Pharmacy, First Hospital of Lanzhou University , Lanzhou, China .|3 School of Pharmaceutical, Lanzhou University , Lanzhou, China .
Xiao
X
Zuo
2 Department of Pharmacy, First Hospital of Lanzhou University , Lanzhou, China .
Zhi
Z
Rao
2 Department of Pharmacy, First Hospital of Lanzhou University , Lanzhou, China .
Hong-Yan
HY
Qin
D000818:Animals; D003106:Colon / Q000166:cytology* / Q000378:metabolism; D004195:Disease Models, Animal; D045786:Diterpenes, Kaurane / Q000008:administration & dosage*; D004759:Enterochromaffin Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy* / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D043183:Irritable Bowel Syndrome / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D045786:Diterpenes, Kaurane; D014409:Tumor Necrosis Factor-alpha; C011959:oridonin; D015847:Interleukin-4; D012701:Serotonin; D007371:Interferon-gamma
colonic cytokine production; enterochromaffin cell; oridonin; postinflammatory irritable bowel syndrome; serotonin