Bak Foong Pill has been used traditionally for treating gynecological disorders for several centuries but also with a newly modified formula for treating postmenopausal symptoms. Cumulating evidence indicates that Bak Foong Pill acts on multi-systems and affects various organ functions. The present review discusses the effects of Bak Foong Pill and its active components on overall body function, with particular focus on the gastrointestinal epithelial ion transport and the related underlying mechanisms.
Animals ; Drugs, Chinese Herbal ; pharmacology ; Epithelial Cells ; metabolism ; Gastrointestinal Tract ; cytology ; Humans ; Ion Transport ; drug effects

AIMTo investigate the mechanisms of anti-cancer effect of resveratrol (Res), and the effects of Res in cell apoptosis. The role of Res playing in mitochondrial permeability transition pore (PTP) induction was studied.

METHODSMitochondria was prepared from the liver of Wistar rats. The effects of Res on oxygen consumption of isolated mitochondria from rat liver was measured with Clark-type electrode and resulted in respiration control rate (RCR). Mitochondrial swelling affected by Res was assessed spectrophotometrically, through the changes in absorbance at 540 nm. The PTP opening was learned from the results. Membrane potential of mitochondia was measured through fluorescence spectrophotometry.

RESULTSRes was shown to inhibit the respiration and decrease the RCR of mitochondria. Res can promote the PTP opening mediated by Ca2+. Res was shown to promote the increase of mitochondial membrane potential mediated by Ca2+ and loss of mitochondial membrane potential.

CONCLUSIONRes was shown to inhibit mitochondial respiration and induce PTP opening of mitochondria. These may be one of the pathways that Res showed anti-cancer action and induce cells apoptosis.

Animals ; Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Calcium ; metabolism ; Female ; Ion Channels ; drug effects ; metabolism ; Membrane Potentials ; drug effects ; Mitochondria, Liver ; drug effects ; physiology ; Mitochondrial Membrane Transport Proteins ; Mitochondrial Swelling ; drug effects ; Rats ; Rats, Wistar ; Stilbenes ; pharmacology

OBJECTIVETo explore the transmembrane transport and metabolism of diammonium glycyrrhizinate in intestines of rats.

METHODAn Ussing Chamber model were used to investigate the transmembrane transport of diammonium glycyrrhizinate (GZ), the concentrations of diammonium glycyrrhizinate and its two metabolites were determined by HPLC.

RESULTThe permeability coefficients of GZ in difference intestinal mucous membranes were ranged from 0.3 x 10(-6) cm x s(-1) to 1.1 x 10(-6) cm x s(-1). The metabolism of GZ in enterocytes during its transport process was negligible. The concentration of diammonium glycyrrhizinate and pH had limit effects on the transport amount and the permeability coefficients of GZ.

CONCLUSIONGZ is a low permeability drug, but it can be absorbed at all segments of the small intestine in rats. Ileum is the major absorption region of GZ.

Animals ; Biological Transport ; Cell Membrane Permeability ; Glycyrrhizic Acid ; metabolism ; pharmacokinetics ; Hydrogen-Ion Concentration ; Intestine, Small ; chemistry ; drug effects ; metabolism ; Male ; Models, Biological ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the effect of extremely low frequency magnetic fields on intracellular calcium concentration ([Ca(2+)]i).

METHODSFura-2 loaded HepG2 cells were exposed to 1.55 mT (average value), 16 Hz pulsed magnetic fields for 60 min and to 300 mT, 2 Hz rotating magnetic fields for 5 min, and then [Ca(2+)]i was measured by fluorescence spectrophotometer. [Ca(2+)]i of HepG2 cells was also measured when they were exposed to 0.9 mT [root mean square (rms)], 16 Hz sinusoidal magnetic fields in real time.

RESULTSThe R values (F(340) nm/F(380) nm) of the control and the exposed group were 2.4519 +/- 0.2378 and 2.5266 +/- 0.2915 respectively after HepG2 cells were exposed to 1.55 mT, 16 Hz magnetic fields, 1.365 0 +/- 0.0626 and 1.3602 +/- 0.0771 respectively to 300 mT, 2 Hz rotating magnetic fields. The ratios of the trendline slope [r((501 - 1,000)) / r((0 - 500))] from the data of R values were 1.1213 +/- 0.4559 and 1.0727 +/- 0.1971 respectively (P > 0.05), and the ratios of the intercept [b((501 - 1,000)) / b((0 - 500))] from the trendline were 0.9912 +/- 0.0098 and 0.9979 +/- 0.0060 (P > 0.05) when HepG2 cells were exposed to the 0.9 mT, 16 Hz sinusoidal magnetic fields.

CONCLUSIONThe effect of extremely low frequency magnetic fields on [Ca(2+)]i of HepG2 cells under the experimental condition has not been found.

Calcium ; metabolism ; Cell Line, Tumor ; drug effects ; metabolism ; radiation effects ; Chelating Agents ; pharmacology ; Egtazic Acid ; pharmacology ; Electromagnetic Fields ; Humans ; Ion Transport ; drug effects ; radiation effects ; Octoxynol ; pharmacology ; Spectrometry, Fluorescence ; Time Factors

OBJECTIVETo investigate the absorption and transport mechanism of magnolol in Caco-2 cell model.

METHODSA human intestinal epithelial cell model Caco-2 cell in vitro cultured was applied to study the absorption and transport of magnolol, the effects of time, donor concentration, P-gp inhibitor verapamil, pH and temperature on the absorption and transport of magnolol were investigated. The determination of magnolol was performed by high performance liquid chromatography, then the values of apparent permeability coefficient (P app ) and P ratio Basolateral-to-Apical (BL-to-AP)/Apical-to-Basolateral (AP-to-BL) were calculated.

RESULTSIn Caco-2 cell model, comparing the amounts of transport of AP-to-BL and BL-to-AP, the latter was larger. At the same donor concentration, either the amounts of transport of AP-to-BL or BL-to-AP increased with increase in donor concentration and incubation time. Verapamil could significantly improve the amounts of transport of AP-to-BL. The transport of AP-to-BL and BL-to-AP depended on temperature, and there was no significant effect of pH on the transport of AP-to-BL.

CONCLUSIONMagnolol could be transported through the intestinal mucosa via a passive diffusion mechanism primarily, coexisting with a carrier-mediated transport, at the same time, the efflux mechanism could be involved.

Biological Transport ; drug effects ; Biphenyl Compounds ; metabolism ; Caco-2 Cells ; Chromatography, High Pressure Liquid ; Humans ; Hydrogen-Ion Concentration ; drug effects ; Intestinal Absorption ; drug effects ; Lignans ; metabolism ; Models, Biological ; Temperature ; Time Factors ; Verapamil ; pharmacology

OBJECTIVETo investigate the mechanism of Shugan Jianpi Recipe (SJR) on the ion transportation of diarrhea predominant irritable bowel syndrome (IBS-D) colon mucosa induced by 5-HT.

METHODSTotally 36 male SD rats were randomly divided into three groups, i. e., the normal group, the model group, and the SJR group, 12 in each group. IBS-D Rat model was induced by intracolonic instillation of acetic acid and restraint stress. After successful modeling, normal saline was given to rats in the normal group and the model group, while SJR was given to those in the SJR group by gastrogavage for 14 days. The short circuit current (lsc) technology was used to measure 5-HT induced lsc changes of the colon mucosa under the actions of drugs and specific blocking agents.

RESULTSThere was no difference in basal current (BC), the potential difference (PD), and transmembrane resistance (TR) of the distal colon among the 3 groups (all P > 0.05). The 5-HT induced short circuit current change (delta lsc) was lower in the model group than in the normal group (P < 0.05), and it was higher in the SJR group than in the model group (P < 0.05). When 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid (DIDS, 500 micromol/L), an Ca(+)-dependent Cl- channel blocker, was added from the epiphragm of the colonic mucosa, the 5-HT induced delta lsc was lower in the model group than in the normal group (P < 0.05), and it was higher in the SJR group than in the model group (P < 0.05). When Na+ was substituted in the epiphragm solution (Na+ free) or amiloride (100 micromol/L) was added from the epiphragm of the colonic mucosa, an epithelial Na+ channel blocker, the 5-HT induced delta lsc was lower in the model group than in the normal group (P < 0.05), and it was higher in the SJR group than in the model group (P < 0.05).

CONCLUSIONSSJR could affect the transmembrane electrolyte transportation of IBS-D rat induced by 5-HT through regulating the secretion of Cl- and HCO3-. The effects might be achieved by the coordination of apical Cl- channel CFTR, basolateral Na(+)-K+ ATPase, sodium-potassium-chloride cotransporter, sodium-bicarbonate cotransporter, Cl-/HCO3- exchanger, as well as K+ channel.

Animals ; Colon ; drug effects ; metabolism ; Diarrhea ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Intestinal Mucosa ; drug effects ; metabolism ; Ion Transport ; drug effects ; Irritable Bowel Syndrome ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley

Hyperoxic ventilation induces detrimental effects on the respiratory system, and ambient oxygen may be harmful unless compensated by physiological anti-oxidants, such as vitamin C. Here we investigate the changes in electrolyte transport of airway epithelium in mice exposed to normobaric hyperoxia and in gulonolacton oxidase knock-out (gulo[-/-]) mice without vitamin C (Vit-C) supplementation. Short-circuit current (Isc) of tracheal epithelium was measured using Ussing chamber technique. After confirming amiloride-sensitive Na+ absorption (DeltaIsc,amil), cAMP-dependent Cl- secretion (DeltaIsc,forsk) was induced by forskolin. To evaluate Ca2+-dependent Cl- secretion, ATP was applied to the luminal side (DeltaIsc,ATP). In mice exposed to 98% PO2 for 36 hr, DeltaIsc,forsk decreased, DeltaIsc,amil and DeltaIsc,ATP was not affected. In gulo(-/-) mice, both DeltaIsc,forsk and DeltaIsc,ATP decreased from three weeks after Vit-C deprivation, while both were unchanged with Vit-C supplementation. At the fourth week, tissue resistance and all electrolyte transport activities were decreased. An immunofluorescence study showed that the expression of cystic fibrosis conductance regulator (CFTR) was decreased in gulo(-/-) mice, whereas the expression of KCNQ1 K+ channel was preserved. Taken together, the CFTR-mediated Cl- secretion of airway epithelium is susceptible to oxidative stress, which suggests that supplementation of the antioxidant might be beneficial for the maintenance of airway surface liquid.
Animals ; Ascorbic Acid Deficiency/*metabolism ; Biological Transport/drug effects ; Chlorides/*metabolism ; Cystic Fibrosis Transmembrane Conductance Regulator/antagonists & inhibitors/drug ; Forskolin/pharmacology ; Hyperbaric Oxygenation ; Hyperoxia/*physiopathology ; Ion Transport/drug effects ; Mice ; Mice, Inbred C57BL ; Mice, Inbred ICR ; Mice, Knockout/metabolism ; Mice, Transgenic ; Microscopy, Fluorescence ; Oxidative Stress ; Oxygen/adverse effects/pharmacology ; Potassium Channels/metabolism ; Respiratory Mucosa/drug effects/*metabolism/secretion ; Sodium ; Sugar Acids/metabolism

The present study investigated the cellular mechanism underlying the effect of ligustrazine on the ion transport in rat distal colon using the short-circuit current (I(SC)) technique. In freshly isolated colonic strips, basolateral addition of ligustrazine stimulated a rise in I(SC), which was resistant to basolateral application of neuronal sodium channel blocker tetrodotoxin (TTX), but inhibited by 55.2% by basolateral pretreatment with prostaglandin inhibitor indomethacin. The ligustrazine-induced I(SC) increase was inhibited by apical application of Cl(-) channel blockers diphenylamine-2,2'-dicarboxylic acid (DPC) and glibenclamide. Basolaterally administered bumetanide, an inhibitor of Na(+)-K(+)-2 Cl(-) cotransporter, inhibited ligustrazine-evoked current increases by 85.2% and basolateral exposure to Ba(2+), a non-specific potassium channels blocker, and blocked the current by more than 90%, indicating that basolateral Na(+)-K(+)-2 Cl(-) cotransporter and K(+) channels played an important role in the effect of ligustrazine. The results suggested that ligustrazine could stimulate rat distal colon (-) secretion that is mediated by basolateral Na(+)-K(+)-2 Cl(-) cotransporter and K(+) channel.
Animals ; Animals, Newborn ; Calcium Channel Blockers ; pharmacology ; Colon ; metabolism ; physiology ; Epithelial Cells ; metabolism ; Evoked Potentials ; drug effects ; In Vitro Techniques ; Intestinal Mucosa ; cytology ; metabolism ; Ion Transport ; drug effects ; Male ; Potassium Channels ; metabolism ; Pyrazines ; pharmacology ; Rats ; Rats, Sprague-Dawley

Drug resistant bacteria is an increasingly urgent challenge to public health. Bacteria adaptation and extensive abuse of antibiotics contribute to this dilemma. Active efflux of antibiotics is employed by the bacteria to survive the antibiotic pressure. Efflux pump is one of the hot spots of current drug related studies and ideal targets for the improvement of treatment. The efflux pumps and related mechanisms of action, regulation of expression and methodologies were summarized. Comparative genomics analyses were employed to elucidate the underlying mechanisms of action and evolution of efflux pump as exemplified by the Mycobacterium in our lab, which is a crucial re-emerging threat to global public health. The pathway and state-of-art drug development of efflux pump related drugs are included too.
ATP-Binding Cassette Transporters ; antagonists & inhibitors ; drug effects ; physiology ; Anti-Bacterial Agents ; metabolism ; pharmacology ; Bacteria ; metabolism ; Drug Resistance, Multiple, Bacterial ; drug effects ; genetics ; Ion Pumps ; antagonists & inhibitors ; drug effects ; physiology ; Membrane Transport Proteins ; drug effects ; physiology ; Multidrug Resistance-Associated Proteins ; drug effects ; physiology ; Mycobacterium ; metabolism

Swelling-activated chloride currents (ICl.swell) are thought to play a role in several physiologic and pathophysiologic processes and thus represent a target for therapeutic approaches. However, the mechanism of ICl.swell regulation remains unclear. In this study, we used the whole-cell patch-clamp technique to examine the role of protein kinase C (PKC) in the regulation of ICl.swell in human atrial myocytes. Atrial myocytes were isolated from the right atrial appendages of patients undergoing coronary artery bypass and enzymatically dissociated. ICl.swell was evoked in hypotonic solution and recorded using the whole-cell patch-clamp technique. The PKC agonist phorbol dibutyrate (PDBu) enhanced ICl.swell in a concentration-dependent manner, which was reversed in isotonic solution and by a chloride current inhibitor, 9-anthracenecarboxylicacid. Furthermore, the PKC inhibitor bis-indolylmaleimide attenuated the effect and 4α-PDBu, an inactive PDBu analog, had no effect on ICl.swell. These results, obtained using the whole-cell patch-clamp technique, demonstrate the ability of PKC to activate ICl,swell in human atrial myocytes. This observation was consistent with a previous study using a single-channel patch-clamp technique, but differed from some findings in other species.
Anthracenes ; pharmacology ; Chloride Channels ; metabolism ; Chlorides ; agonists ; antagonists & inhibitors ; metabolism ; Culture Media ; metabolism ; pharmacology ; Dose-Response Relationship, Drug ; Evoked Potentials ; drug effects ; physiology ; Heart Atria ; cytology ; drug effects ; metabolism ; Humans ; Hypotonic Solutions ; metabolism ; pharmacology ; Indoles ; pharmacology ; Ion Transport ; drug effects ; Maleimides ; pharmacology ; Myocytes, Cardiac ; cytology ; drug effects ; metabolism ; Patch-Clamp Techniques ; Phorbol 12,13-Dibutyrate ; pharmacology ; Primary Cell Culture ; Protein Kinase C ; metabolism