Signaling mechanism underlying the stimulatory effects of bak foong pills and its active components on gastrointestinal epithelia.

摘要

The study systematically examined the effects, as well as the underlying signaling mechanisms, of a traditional Chinese medicine, Bak Foong Pills ( BFP), its modified formula, Menoease Pills ( MP) and its active compound, tetramethylpyrazine (TMP, also named Ligustrazine), on the GI tract anion secretion. The work was conducted using freshly isolated native colonic mucosa, and different colonic epithelial and pancreatic duct epithelial cell lines in conjunction with electrophysiological techniques, intracellular Ca2+ and cAMP measurement, as well as semi-quantitative RT-PCR analysis. In vivo study on animal pancreatic secretion was also conducted. The major findings of the study include: (1) BFP, MP and TMP exert a stimulatory effect on colonic and pancreatic anion secretion including both Cl- and HCO3-; (2) differential Cl- and HCO3- secretion could be stimulated by different dosages of TMP, which is mediated by different colonic epithelial cell types; (3) the stimulatory effect is predominantly mediated by cAMP and Ca2+ signaling pathways; (4) apical cAMP-dependent Cl- channel, CFTR, and basolateral Ca2+-activated K+ channels were the major transporting mechanisms involved; and (5) the epithelial barrier function could be improved after long term treatment with MP and TMP. The results of the study not only demonstrate for the first time the pharmacological action of BFP and its active compound on the GI epithelial anion secretion and barrier function but also contribute to the basic and new knowledge of GI tract physiology, particularly, different roles of different types of colonic cells in mediating different anion secretion, and the particular types of apical and basolateral ion channels involved. The work has also contributed to a better understanding of the action of traditional Chinese medicine on epithelial ion transport, with reference to gastrointestinal secretion.; With a long history of clinical use but few reported scientific studies, the working of most traditional Chinese medicine, including BFP, has remained largely a mystery. It is hoped that the scientific work and language presented here may enable a new understanding of traditional Chinese medicine and serve as a "bridge" between traditional Chinese medicine and Western medicine.