The blood-brain barrier (BBB) protects the brain against unwanted substances, while, at the same time, limits the transport of many drugs into the brain. Aromatic refreshing traditional Chinese medicine (TCM) can induce resuscitation and modify the permeability of BBB, promoting other drugs entering into the brain with brain protection effect. This paper mainly reviews the research progress in regulation effects and mechanism of usual aromatic refreshing TCM, such as borneol, moschus, styrax, benzoinum and Tatarinow Sweetflag Rhizome, on BBB permeability. To broaden the application of these drugs in modern pharmaceutics in the future, the relatively research should emphasis on combining aromatic refreshing TCM with new formulations and technologies in pharmaceutics, providing novel promising strategies for brain diseases therapy.
Animals ; Blood-Brain Barrier ; drug effects ; metabolism ; Humans ; Medicine, Chinese Traditional ; methods ; Permeability ; drug effects

This article reviews the recent studies on H2O2 adaptation of Saccharomyces cerevisiae. When the cell exposed in the H2O2 sub-lethal doses, the plasma membrane permeability decreased, meanwhile the plasma membrane fluidity is minished. These changes resulted in a gradient across the plasma membrane, which conferring a higher resistance to oxidative stress. Recent work has also shown that the yeast cells adapted to H2O2 would lead to several changes in the expression of genes coding the key enzymes involved in the biosynthesis of lipid profile and in the organization of lipid microdomains of the plasma membrane, which finally decreased its' permeability and fluidity. The reorganization of the plasma membrane might be the major mechanism of the H2O2 adaptation. Once the yeast cells adapted to the external H2O2, changes in plasma occurred. The H2O2 dependent signaling pathways in the plasma membrane might be activated by high levels of H2O2. But the details of the signaling events should still be further studies.
Cell Membrane ; drug effects ; metabolism ; Cell Membrane Permeability ; drug effects ; Hydrogen Peroxide ; pharmacology ; Membrane Fluidity ; drug effects ; Saccharomyces cerevisiae ; cytology ; drug effects ; Signal Transduction ; drug effects

Ca2+ at 1.64 mmol/L markedly increased ethanol tolerance of a self-flocculating fusant of Schizosaccharomyces pombe and Saccharomyces cerevisiae. After 9 h of exposure to 20% (V/V) ethanol at 30 degrees C , no viability remained for the control whereas 50.0% remained for the cells both grown and incubated with ethanol in Ca2+ -added medium. Furthermore, when subjected to 15% (V/V) ethanol at 30 degrees C, the equilibrium nucleotide concentration and plasma membrane permeability coefficient (P' ) of the cells both grown and incubated with ethanol in Ca2+ -added medium accounted for only 50.0% and 29.3% those of the control respectively, indicating that adding Ca2+ can markedly reduce plasma membrane permeability of yeast cells under ethanol stress as compared with the control. Meanwhile, high viability levels acquired by the addition of Ca2+ exactly corresponded to the striking decreases in extracellular nucleotide concentration and P' achieved with identical approach. Therefore, the enhancing effect of Ca2+ on ethanol tolerance of this strain is closely related to its ability to decrease plasma membrane permeability of yeast cells subjected to ethanol stress.
Calcium ; pharmacology ; Cell Membrane ; drug effects ; metabolism ; Cell Membrane Permeability ; drug effects ; Ethanol ; pharmacology ; Saccharomyces cerevisiae ; drug effects ; growth & development ; metabolism ; Schizosaccharomyces ; drug effects ; growth & development ; metabolism ; Temperature

OBJECTIVETo study the effects of domoic acid (DA) on membrane function of primary cultured rat glial cell.

METHODSAfter the glial cells were treated with 6.4 x 10(-2), 6.4 x 10(-3) and 6.4 x 10(-4) micromol/L DA for 24 h, the activities of Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase, the membrane fluidity and the permeability were measured to reflect the membrane function.

RESULTSAfter treatment of DA for 24 h, the activities of Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase were inhibited significantly, the membrane fluidity decreased and the membrane permeability increased. The fluorescence polarization and microviscosity in the low, middle and high dosage treatment groups were 0.0626 +/- 0.0051, 0.0685 +/- 0.0097, 0.0648 +/- 0.0086 and 0.3154 +/- 0.0298, 0.3510 +/- 0.0571, 0.3286 +/- 0.0504 respectively, compared with the control group (0.0481 +/- 0.0069 and 0.2338 +/- 0.0372) (P < 0.01).

CONCLUSIONDA has obvious effects on membrane function of rat glial cells and may cause further injury on the cells.

Animals ; Cell Membrane ; drug effects ; Cell Membrane Permeability ; drug effects ; Cells, Cultured ; Kainic Acid ; analogs & derivatives ; pharmacology ; Membrane Fluidity ; drug effects ; Neuroglia ; drug effects ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the factors that affect mucosal absorption of gardenia extract.

METHODTake vitro frog skin as a model to study the vitro mucosal permeation. The impacts of the osmotic pressure and the pH value of permeation medium on the Papp of the Jasminoidin were studied, and the effect of frog skin on the stability of Jasminoidin was investigated also.

RESULTThe Papp of Jasminoidin were (0.53 +/- 0.01), (0.21 +/- 0.05), (0.44 +/- 0.12), (0.42 +/- 0.13), (0.26 +/- 0.03) cm x min(-1) by using the normal saline (pH 6.88), pure water, 1.8 % NaCl solution, normal saline (pH 4.05) and normal saline (pH 10.05) as permeation medium for each. The accumulated permeation rate was (55.69 +/- 9.81)% by 12 h, using normal saline as permeation medium respectively, and there was no obvious time lag. Jasminoidin began to degrade around 8 h by affectedof frog skin, the constant of degradation rate (K) was 1.999, and the t1/2 was 0.347 h.

CONCLUSIONThe mucosal permeability of gardenia extract by using the vitro model of frog skin is good, and consistent with zero level absorption process. The osmotic pressure and pH value significantly affected the permeation and the isotonic and partial neutral permeation medium are more conducive to the permeation and absorption of Jasminoidin. The degradation effect of frog skin to the Jasminoidin will not affect mucosal permeation research. In vitro model of frog skin is a suitable way to simulate mucosal permeation process of the gardenia extract.

Gardenia ; chemistry ; Hydrogen-Ion Concentration ; Mucous Membrane ; drug effects ; physiology ; Permeability ; drug effects ; Plant Extracts ; chemistry ; pharmacology ; Skin ; drug effects ; Skin Absorption ; drug effects ; physiology ; Solubility

OBJECTIVETo investigate the effect of c-Met inhibitor cabozantinib (XL-184) in inhibiting Listeria monocytogenes (LM) from invading Caco-2 cells to reduce the cell injury.

METHODSThe cell invasion capacity of LM was assayed in Caco-2 cells incubated with different doses of XL-184 for different durations. Caco-2 cells incubated with XL-184 were seeded on the upper room of the transwell chamber, and the cell monolayer was exposed to LM infection followed by addition of horseradish peroxidase (HRP). The trans-epithelial electric resistance (TEER), HRP concentration and LM colony-forming unit (CFU) were measured in the cell monolayer. Fluorescent staining was used to evaluate the cell viability, and LDH release from the cells was examined to assess the changes in cell membrane permeability.

RESULTSXL-184 significantly decreased LM invasion rate in Caco-2 cells in a dose- and time-dependent manner (P=0.000), and this effect was enhanced by co-incubation of the cells with ampicillin (P<0.05). In the cell membrane permeability assay in the monolayer cells, XL-184 markedly inhibited LM-induced reduction of TEER (P<0.05) and significantly suppressed LM-induced enhancement of cell membrane permeability shown by reduced HRP concentration and LM count in the lower chamber (P=0.000). The cells infected with LM showed significantly lowered cell viability, which was rescued by XL-184 (P<0.01); XL-184 also dose-dependently reduced LDH release from the cells (P<0.05).

CONCLUSIONSXL-184 can suppress LM invasion in Caco-2 cells to reduce the cell injury, suggesting its value as a promising candidate agent for prevention and treatment of LM infections.

Anilides ; pharmacology ; Caco-2 Cells ; Cell Membrane Permeability ; drug effects ; Cell Survival ; Humans ; Listeria monocytogenes ; drug effects ; Pyridines ; pharmacology

OBJECTIVETo prepare sparfloxcain lactate (SPLX) loaded liposomes and study its corneal penetration and bacterial inhibitory in vitro.

METHODSLiposomal SPLX (mass ratio of phospholipids/ cholesterol/drug at 18:6:1) was prepared by pH-gradients. The transcorneal penetration experiments of liposomal SPLX were performed in modified Franz's cells with the rabbit's corneal. The concentration of SPLX was determined by high-performance liquid chromatography. The penetration parameters were calculated. The in vitro antibacterial activities on S. aureus, P. aeruginusa, E. coli, and B. subtilis were determined by two fold dilutions.

RESULTSThe entrapment efficiency of SPLX in the liposomes by pH-gradients was (81.61 +/- 1.98)%, which was significantly higher than that by film dispersion method (11.48 +/- 0.86)% and reverse evaporating method (18.64 +/- 1.05)% (both P < 0.01). The permeability coefficient and corneal deposition quantity of SPLX liposomes were 1.65- and 4.98-folds higher as compared with those of free drug solutions. The minimal inhibitory concentrations (MICs) of liposomal SPLX against S. aureus, P. aeruginosa, E. coli, and B. subtilis were 1/4, 1/2, 1/1, 1/17 times lower than those of free drug, respectively, and the minimal bactericide concentrations (MBCs) were 1/4, 1/2, 1/1, 1/4 times lower than those. In addition, the time-kill values of liposomal SPLX were better than those of free.

CONCLUSIONThe pH gradient technique is suitable for preparing SPLX liposomes, which can improve the transcorneal penetration and antibacterial activity of SPLX in vitro.

Animals ; Anti-Bacterial Agents ; chemistry ; pharmacology ; Bacteria ; drug effects ; Cornea ; chemistry ; drug effects ; Female ; Liposomes ; chemistry ; pharmacology ; Male ; Permeability ; Rabbits

OBJECTIVETo investigate a possibility to improve the security of pulse-activating injection by comparing the difference of pseudoanaphylactoid reactions (PR) induced by pulse-activating injection before and after improving technology.

METHODThe analysis of vascular permeability of the mice's ears: ICR mouse were divided into different test groups, and intravenously injected with solutions of different concentration of pulse-activating injection before and after improving technology, positive control Compound 48/80 and 5% glucose injection. All test substances were mixed with 0. 4% Evans blue. The reaction and vascular permeability of the ears were observed and measured 30 min after injection. The vascular permeability of the rat's skin: the rats were intravenous injected with 0. 6% Evans blue normal saline solution first, 10 minutes later, the same test substances were intradermal injected into the back of rats, there are 16 injected spots in the back of rat. The rats were sacrificed and the diameter of locus ceruleus and the content of Evans blue leaked out were measured 20 min after injection.

RESULTPulse-activating injection before improving technology with dose of 16.7 mL x kg(-1) ( in 1.67 times the clinical dose ) caused obvious vascular hyperpermeability in ICR mice. In the group of pulse-activating injection before improving technology with dose of 10 mL x kg(-1) (in clinic equivalent dose), no obvious vascular hyperpermeability in the ears were observed. The degrees of vascular hyperpermeability in the group of pulse-activating injection after improving technology with dose of 16.7 mL x kg(-1) were more lessen than the same dose of injection before improving technology. Pulse-activating injection before improving technology caused obvious exudation, oedema locus ceruleus in the injection site of rat's back, and it showed a certain dose-effect relation. Pulse-activating injection after improving technology caused locus ceruleus in the injection site too, but the diameters of the locus ceruleus were shorter than the diameters in the group of pulse-activating injection before improving technology, and the contents of leaked out Evans blue were fewer. All of these showed that PR of skin induced by pulse-activating injection after improving technology is alleviated.

CONCLUSIONPulse-activating injection before improving technology cause obvious vascular hyperpermeability, but the same dose of pulse-activating injection after improving technology can't cause obvious vascular hyperpermeability. The result indicated that the pulse-activating injection before improving technology can cause PR, improving technology can lessen the degree of PR induced by the injection.

Anaphylaxis ; chemically induced ; Animals ; Capillary Permeability ; drug effects ; Injections, Intravenous ; methods ; Male ; Mice ; Mice, Inbred ICR ; Rats ; Skin ; drug effects

OBJECTIVETo study the percutaneous permeability of patches Shangshi Zhitong on different kinds of bases with the permeation percentage of brucine, strychnine and atropine.

METHODUsing modified Franz difusion to investigate the penetration quantity of brucine, strychnine and atropine. The contents of brucine, strychnine and atropine were determined by HPLC.

RESULTThe average accumulative permeation percentage of brucine, strychnine and atropine on new base were 53.25%, 74.52% were 34.32%, respectively, and on old base are 54.90%, 50.24%, 46. 54%, respectively.

CONCLUSIONThe new base benefits the lipophilic drugs and releases more stably.

Animals ; Drugs, Chinese Herbal ; analysis ; pharmacokinetics ; Male ; Permeability ; Rats ; Rats, Sprague-Dawley ; Skin ; drug effects ; metabolism

OBJECTIVETo investigate the effect of thymic stromal lymphopoietin (TSLP) on the permeablily of monolayer bronchial epithelial cells in vitro.

METHODSCultured human bronchial epithelial cell line 16HBE was exposed to 0.1 or 1 ng/ml TSLP for 0, 0.5, 6, 12, or 24 h, and the epithelial monolayer permeability was assessed by measuring transepithelial electrical resistance (TER), permeability to FITC-labeled dextran (FITC-DX) and expression of E-cadherin.

RESULTSCompared with the control cells group, 16HBE cell monolayer showed significantly increased TER (P<0.001) and decreased FITC-DX fluorescence in the lower chamber (P<0.05) following exposure to 0.1 and 1 ng/ml TSLP, but these changes were not dose-dependent. Exposure to 0.1 ng/ml TSLP resulted in significantly increased expression of E-cadherin. The 16HBE monolayer exposed to 0.1 ng/ml TSLP for 24 h showed the most obvious increase of TER and E-cadherin expression (P<0.05); FITC-DX fluorescence level was markedly decreased after TSLP exposure for 12 h and 24 h (P<0.05), and the effect was more obvious in 12 h group.

CONCLUSIONTSLP can protect the barrier function of normal bronchial epithelial cells in vitro.

Bronchi ; cytology ; Cadherins ; metabolism ; Cell Line ; Cytokines ; pharmacology ; Epithelial Cells ; drug effects ; Humans ; Permeability