Hexane extract of Poncirus trifoliata (L.) Raf. stimulates the motility of rat distal colon

Aim of the study: Poncirus trifoliata (L.) Raf (Rutaceae, PT) has been commonly used for treating gastrointestinal (GI) disorders in Korean traditional medicine, but its pharmacological roles in the regulation of colonic motility have not been clarified. This study investigated the regulatory effects of PT on the colonic motility. Materials and methods: Immature fruits of PT were sequentially partitioned with MeOH, n-hexane, CHCl3, EtOAc, n-BuOH and H2O, and the effects of PT extracts on the contractility of colonic strips and colonic luminal transit in rats were measured in vitro and in vivo, respectively. Results: Among six different extracts, only hexane extract of PT (PTHE) dose-dependently increased the low frequency contraction of longitudinal muscle in distal colonic strips, and the ED50 value was revealed to be 0.71 mu g/ml. The contractile patterns induced by PTHE were remarkably different from those caused by acetylcholine (ACh) and serotonin (5-HT). The stimulatory effects of PTHE on the whole distal colonic strips were more prominent than on the mucosa/submucosa-denuded segments. The M-2 receptor-preferring, methoctramine (0.5 mu M), and M-3 receptor-preferring antagonist, 4-DAMP (0.5 mu M) significantly blocked the PTHE (1 mu g/ml)-induced contraction of distal colon longitudinal muscles, whereas the 5-HT receptor antagonists (1.0 mu M, alone or in combination) selective for 5-HT3 (ondansetron), 5-HT4 (GR113808) and 5-HT1.2.5-7 (methysergide) receptors did not change the PTHE (1 mu g/ml)-induced contractility of distal colon longitudinal muscles. SNAP (0.1 mM), a NO donor, enhanced the stimulatory effects of PTHE on the longitudinal muscle of distal colon, but L-NAME(0.1 mM), a NO synthesis inhibitor, had no effects. PTHE (10-100 mg/kg) caused a dose-dependent increase of colonic luminal transit. Conclusions: Collectively, these findings suggest that PTHE specifically acts on the longitudinal muscle of distal colon in rats, and these stimulatory effects are likely mediated, at least, by activation of acetylcholinergic M-2 and M-3 receptors. (C) 2009 Elsevier Ireland Ltd. All rights reserved.