Traditional Chinese formula, lubricating gut pill, improves loperamide-induced rat constipation involved in enhance of Cl- secretion across distal colonic epithelium

Aim of the study: Lubricating gut pill (LGP), a traditional Chinese formula, was widely used for the treatment of chronic constipation, especially in the elderly, in China. However, it is unclear whether LGP-induced laxative and/or lubricating effect is involved in water and electrolytes transport in distal colonic epithelium. Materials and methods: The present study was designed to evaluate the effect of LGP on Cl- secretion across rat distal colonic epithelium mounted in Ussing chambers, and on a rat constipation model induced by loperamide, respectively. Results: Application of LGP in the apical side elicited a sustained increase in short circuit current (I-SC) response in a concentration-dependent manner. Evidence that LGP-stimulated I-SC was due to Cl- secretion is based on inhibition of current by (a) a Na+-K+-2Cl(-) cotransporter inhibitor bumetanide, (b) removal of Cl- ions in bath solution, and (c) the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel blocker DPC, suggesting that a apical cAMP-dependent Cl- channel was activated. LGP-stimulated I-SC was also strongly inhibited by pretreatment with clotrimazole, indicating that the basolateral K+ channel was also involved in maintaining this cAMP-dependent Cl- secretion. Pretreatment of tissues with indomethacin, but not atropine, tetrodotoxin or hexamethonium, inhibited LGP-induced response. In a rat constipation model, oral administration with LGP was significantly restored number of fecal pellets, water content and mucus secretion compared with loperamide-treated group alone. Conclusions: LGP enhances Cl- secretion that is mostly mediated through the release of cyclooxygenase metabolites, by which provided an osmotic force for the subsequent laxative action observed in the rat constipation model. (C) 2010 Elsevier Ireland Ltd. All rights reserved.