The Inhibition Effect Of Ethanol Extract From Polygonum Bistorta L. On Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel

Chinese herbal Polygonum bistorta is the dry rhizome from Polygonum bistorta L..Polygonum bistorta has the efficacy of heat-clearing and detoxifying, detumescence andhemostasis so widely used in clinical diseases such as snake bite, carbuncle swollen andscrofula. Recent researches found Polygonum bistorta has variety of favorable biologicalactivites such as antisepsis and anti-inflammation, analgesia, central inhibition, antioxidation,antidiarrhea, antitumor, etc. In the antidiarrheal research Polygonum bistorta has goodefficacy for the treatments of infantile diarrhea, damp-heat dysentery, as antidiarrheal herbscould prevent diarrhea and effectively improve the growth performance of piglets. However,there are few pharmacology studies on it and the active ingredients responsible for theirtherapeutic effectiveness remain unkown.Cystic fibrosis transmembrane conductance regulator (CFTR) belongs to the adeninenucleotide-binding cassette (ABC) transporter family, and is the only anion channel of ABCsuperfamily. CFTR is extensively expressed on the luminal surface of serous epithelial cells,which regulates the chloride ion transport across epithelial cells. It has been confirmed thatCFTR palys a vital role in the absorption and secretion of electrolytes and fluid in submucosalglands. In secretory diarrheas such as cholera this balance is perturbed such that fluidsecretion predominates. CFTR chloride channel dysfunction may inhibite choleratoxin-induced intestinal fluid secretion, some CF patients can survive during cholera epidemic.The CFTR inhibitors indentified are important not only in CFTR channel gating mechanismstudies, physiological and pathological function investigations, but also important inpathological mechanism investigations and therapy of some CFTR-related diseases includingsecretory diarrhea.Our study used an established cell-based fluorescence quenching assay to identify theinhibition activity of Polygonum bistorta in CFTR chloride channel from500herbal plantsand isolated the active ingredients via bioactivity-directed and column chromatography.Cell-based fluorescent assay found that Polygonum bistorta dose-dependently blockedCFTR-mediated iodide influx, and the effect was rapid and irreversible. Short-circuit currentexperiment in rat colonic mucosa and intestinal closed-loop model in mice further confirmedthat Polygonum bistorta can inhibit CFTR-mediated ion transport and liquid secretion. Ourstudy found that ethanol extract of Polygonum bistorta has the activity of inhibiting CFTR chloride channel for the first time, and it might be a potential therapeutic for the treatment ofsecretory diarrhea.