Analgesic effect of Coptis chinensis rhizomes (Coptidis Rhizoma) extract on rat model of irritable bowel syndrome

Brian Berman,Harry H.S Fong,Yungwui Tjong,Joseph J.Y Sung,Chuntao Che,Siupo Ip,Lixing Lao

doi:10.1016/j.jep.2011.04.007

Abstract

Coptis chinensis rhizomes (Coptidis Rhizoma, CR), also known as "Huang Lian", is a common component of traditional Chinese herbal formulae used for the relief of abdominal pain and diarrhea. Yet, the action mechanism of CR extract in the treatment of irritable bowel syndrome is unknown. Thus, the aim of our present study is to investigate the effect of CR extract on neonatal maternal separation (NMS)-induced visceral hyperalgesia in rats and its underlying action mechanisms. Male Sprague-Dawley rats were subjected to 3-h daily maternal separation from postnatal day 2 to day 21 to form the NMS group. The control group consists of unseparated normal (N) rats. From day 60, rats were administrated CR (0.3, 0.8 and 1.3 g/kg) or vehicle (Veh; 0.5% carboxymethylcellulose solution) orally for 7 days for the test and control groups, respectively. Electromyogram (EMG) signals in response to colonic distension were measured with the NMS rats showing lower pain threshold and increased EMG activity than those of the unseparated (N) rats. CR dose-dependently increased pain threshold response and attenuated EMG activity in the NMS rats. An enzymatic immunoassay study showed that CR treatment significantly reduced the serotonin (5HT) concentration from the distal colon of NMS rats compared to the Veh (control) group. Real-time quantitative PCR and Western-blotting studies showed that CR treatment substantially reduced NMS induced cholecystokinin (CCK) expression compared with the Veh group. These results suggest that CR extract robustly reduces visceral pain that may be mediated via the mechanism of decreasing 5HT release and CCK expression in the distal colon of rats.

Highlights

Irritable bowel syndrome (IBS) is a prevalent chronic functional gastrointestinal disorder affecting approximately 10%-15% of the world’s population (Clarke et al, 2009; Cremonini and Talley, 2005)
These results suggest that Coptidis Rhizoma (CR) extract robustly reduces visceral pain that may be mediated via the mechanism of decreasing 5HT release and CCK expression in the distal colon of rats
Ca. 95% of 5HT are found in the GI tract, 90% of which is secreted from enterchromaffin (EC) cells and the remaining 10% are found in the serotonergic neurons of the myenteric plexus (Bertrand and Bertrand, 2010; Sikander et al, 2009)

Summary

Introduction

Irritable bowel syndrome (IBS) is a prevalent chronic functional gastrointestinal disorder affecting approximately 10%-15% of the world’s population (Clarke et al, 2009; Cremonini and Talley, 2005). According to The Rome Committee for the classification of functional gastrointestinal disorders, IBS is characterized by recurrent abdominal pain or discomfort, change in the frequency of stool form, bloating, abnormal bowel habits (diarrhea, constipation or a combination of both) and related symptoms (Crowell et al, 2005; Sohrabi et al, 2010; Spiegel et al, 2010). These symptoms are thought to be associated with a disturbance of the brain-gut axis which contributes to visceral hypersentivity and dysmotility (Akbar et al, 2009; Manabe et al, 2009). The 5HT signaling pathway is implicated in the development of IBS

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