Cellular Signaling Mechanisms Underlying Pharmacological Action of Bak Foong Pills on Gastrointestinal Secretion.

Abstract

Bak Foong Pills (BFP, also known as Bai Feng Wan)is an over-the-counter traditional Chinese medicine (China registration No. Z980035) that has long been used for treating gynecological disorders and improving of overall body functions, including gastrointestinal (GI) function [1]. However, the cellular signaling mechanism underlying BFP action, especially on the GI tract, has not been elucidated.Secretagogue-induced Cl Ϫ secretion by the GI tract is important because Cl Ϫ secretion provides an essential driving force for the lubrication of intestinal contents during regular bowl movements or the flushing of microbial organisms or artificial irritants in host defense responses [2,3]. Epithelial Cl Ϫ channels, especially the cAMP-activated Cl Ϫ channels, play an important role in regulating and maintaining the normal physiological functions of the GI tract. The abnormal regulation of Cl Ϫ channels, such as by cholera toxin, Abstract: Bak Foong Pills (BFP, also known as Bai Feng Wan) is an over-the-counter traditional Chinese medicine that has long been used for treating gynecological disorders and improving overall body functions, including gastrointestinal (GI) function. However, the cellular signaling mechanism underlying BFP action, especially on the GI tract, has not been elucidated. In the present study, the human colonic epithelia cell line T 84 was used as a model to investigate the effect of BFP ethanol extract on ion transport in conjunction with the short-circuit current (I SC ) technique. The results showed that the apical addition of BFP extract produced a concentration-dependent (10-1,000 g/ml, EC 50 ϭ120 g/ml) increase in I SC . The maximal response was observed at 500 g/ml with an increase in I SC of 24.4Ϯ2.3 A/cm 2 and apical conductance. The BFP-induced I SC was not observed when extracellular Cl Ϫ was replaced or when treated with Bumetanide (100 M), an inhibitor of the NaϪ cotransporter. The BFP-induced I SC was insensitive to the Na ϩ channel blocker, amiloride, but partially inhibited by the Cl Ϫ channel blocker, DIDS (100 M), and completely blocked by DPC (2 mM) or glibenclamide (1 mM) with a significant reduction in the apical conductance. The BFP-induced I SC could be mimicked by forskolin (10 M), but inhibited by a pretreatment of the cells with adenylate cyclase inhibitor, MDL-12330A (10 M). Pretreatment with EGTA (5 mM) and thapsigargin (10 M) decreased the BFP-induced I SC by 10%. These results demonstrated that BFP ethanol extract exerted a stimulatory effect on gastrointestinal Cl Ϫ secretion by predominantly activating adenylate cyclase and apical cAMP-dependent Cl Ϫ channels, with minor contributions from calcium-dependent Cl Ϫ channels. The effect of BFP may be explored to treat GI disorders such as constipation.

Effects of Bak Foong Pill on Blood Coagulation and Platelet Aggregation.

“…Clinical indications also suggest that BFP has beneficial effect on overall body functional systems including the cardiovascular, digestive system as well as the reproductive system. Our previous studies has demonstrated estrogenic effect of BFP and it beneficial effect on gastrointestinal secretion, 7,8) as well as preventing/delaying development of hypertension in spontaneous hypertension rats (Zhou et al unpublished data). In order to evaluate the effect of BFP on the cardiovascular system, we undertook the present study to investigate its effect on blood coagulation and the BFP-E-ext (76 g).…”

Effects of Bak Foong Pills and Menoease Pills on White Blood Cell Distribution in Old Age Female Rats

“…Rats aged 18 months have been demonstrated to be suitable model for postmenopausal-like and old age animals. 21,22) Animals were supplied by the Laboratory Animal Service Centre of the Chinese University of Hong Kong. Animals were maintained in an air-conditioned room with controlled temperature of 24Ϯ2°C and humidity of 55Ϯ15%, in a 12 h light/dark cycle.…”

“…BFP has long been used as a remedy to treat gynaecological disorders, such as dysmenorrhoea, irregular menstrual cycle and irregular bleeding. Clinical indications have suggested that BFP has beneficial effects on overall body function and our previous studies have demonstrated effects of BFP, most of which to various extents are estrogen-related, on improving blood circulation, 20) gastrointestinal secretion 21) and reduce the chance of cardiovascular hypertension. 22) Menoease Pills (MBFP), is a new commercially available BFP-derived formula, with major ingredients including:…”

Differential Cl-and HCO3-mediated anion secretion by different colonic cell types in response to tetromethylpyrazine

“…TMP has been proposed to act as an inhibitor of phosphodiesterase (PDE) and thereby it increases intracellular cAMP [15] . We have recently demonstrated a stimulatory effect of a TMP-containing herbal formula on the anion secretion in human colonic [17] and pancreatic duct cell lines [18] , indicating the involvement of cAMP and activation of CFTR. The present study aimed to compare the stimulatory effects of TMP on colonic anion secretion in different colonic cell types, T84 and Caco-2, as well as freshly isolated rat colonic mucosa, in an attempt to assess the different contribution of these two cell types to colonic anion secretion.…”