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

Abstract

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.

• Authors: Dazheng Wu, Xinhong Wang, Jiyan Zhou, Jianye Yuan, Bo Cui, Rui An, Zhibi Hu
• Journal: Journal of ethnopharmacology (J Ethnopharmacol) Vol. 130 Issue 2 Pg. 347-53 (Jul 20 2010) ISSN: 1872-7573 [Electronic] Ireland
• PMID: 20488235 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Chlorides
• Cholinergic Antagonists
• Cyclooxygenase Inhibitors
• Drugs, Chinese Herbal
• Laxatives
• Potassium Channel Blockers
• Sodium Potassium Chloride Symporter Inhibitors
• Cystic Fibrosis Transmembrane Conductance Regulator
• Loperamide
• Cyclic AMP
• Prostaglandin-Endoperoxide Synthases

Topics

• Animals
• Chlorides (metabolism)
• Cholinergic Antagonists (pharmacology)
• Colon (drug effects, metabolism)
• Constipation (chemically induced, drug therapy, physiopathology)
• Cyclic AMP (metabolism)
• Cyclooxygenase Inhibitors (pharmacology)
• Cystic Fibrosis Transmembrane Conductance Regulator (antagonists & inhibitors, metabolism)
• Defecation (drug effects)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drugs, Chinese Herbal (pharmacology)
• Intestinal Mucosa (drug effects, metabolism)
• Intestinal Secretions (metabolism)
• Laxatives (pharmacology)
• Loperamide
• Male
• Medicine, Chinese Traditional
• Membrane Potentials
• Osmosis
• Potassium Channel Blockers (pharmacology)
• Prostaglandin-Endoperoxide Synthases (metabolism)
• Rats
• Rats, Wistar
• Sodium Potassium Chloride Symporter Inhibitors (pharmacology)