title: Modulation of Chloride Channel Functions by the Plant Lignan Compounds Kobusin and Eudesmin.
abstract: Plant lignans are diphenolic compounds widely present in vegetables, fruits, and grains. These compounds have been demonstrated to have protective effect against cancer, hypertension and diabetes. In the present study, we showed that two lignan compounds, kobusin and eudesmin, isolated from Magnoliae Flos, could modulate intestinal chloride transport mediated by cystic fibrosis transmembrane conductance regulator (CFTR) and calcium-activated chloride channels (CaCCs). The compounds activated CFTR channel function in both FRT cells and in HT-29 cells. The modulating effects of kobusin and eudesmin on the activity of CaCCgie (CaCC expressed in gastrointestinal epithelial cells) were also investigated, and the result showed that both compounds could stimulate CaCCgie-mediated short-circuit currents and the stimulation was synergistic with ATP. In ex vivo studies, both compounds activated CFTR and CaCCgie chloride channel activities in mouse colonic epithelia. Remarkably, the compounds showed inhibitory effects toward ANO1/CaCC-mediated short-circuit currents in ANO1/CaCC-expressing FRT cells, with IC50 values of 100 μM for kobusin and 200 μM for eudesmin. In charcoal transit study, both compounds mildly reduced gastrointestinal motility in mice. Taken together, these results revealed a new kind of activity displayed by the lignan compounds, one that is concerned with the modulation of chloride channel function.
authors.affiliation: School of Life Sciences, Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University Dalian, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: School of Life Sciences, Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University Dalian, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
authors.affiliation: School of Life Sciences, Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University Dalian, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.affiliation: School of Life Sciences, Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University Dalian, China.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Cao
authors.affiliation: College of Basic Medical Sciences, Dalian Medical University Dalian, China.
authors.forename: Tonghui
authors.initials: T
authors.lastname: Ma
authors.affiliation: School of Life Sciences, Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University Dalian, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
keywords: ANO1/CaCC; CFTR; CaCCs; eudesmin; kobusin; short-circuit current