iridoids and muscone

Geniposide is widely used in the treatment of cerebral ischemic stroke and cerebrovascular diseases for its anti-thrombotic and anti-inflammatory effects. Recent studies demonstrated that geniposide could be absorbed promptly and thoroughly by intranasal administration in mice and basically transported into the brain. Here, we explored its transport mechanism and the effect of borneol and muscone on its transport by human nasal epithelial cell (HNEC) monolayer. The cytotoxicity of geniposide, borneol, muscone and their combinations on HNECs was evaluated by the MTT assay. Transcellular transport of geniposide and the influence of borneol and muscone were studied using the HNEC monolayer. Immunostaining and transepithelial electrical resistance were measured to assess the integrity of the monolayer. The membrane fluidity of HNEC was evaluated by fluorescence recovery after photobleaching. Geniposide showed relatively poor absorption in the HNEC monolayer and it was not a P-gp substrate. Geniposide transport in both directions significantly increased when co-administrated with increasing concentrations of borneol and muscone. The enhancing effect of borneol and muscone on geniposide transport across the HNEC may be attributed to the significant enhancement on cell membrane fluidity, disassembly effect on tight junction integrity and the process was reversible. These results indicated that intranasal administration has good potential to treat cerebrovascular diseases.

Topics: Actins; Biological Transport; Camphanes; Cell Membrane Permeability; Cell Survival; Cells, Cultured; Chromatography, High Pressure Liquid; Cycloparaffins; Epithelial Cells; Humans; Iridoids; Microscopy, Fluorescence; Nasal Mucosa

To study the effects of borneol and muscone on membrane fluidity, membrane potential, Na+, K(+)-ATPase activity and calcium ions of blood brain barrier (BBB) model cells (MDCK and MDCK-MDR1) for exploring the mechanism of aromatics.. MDCK and MDCK-MDR1 cells were incubated and the experiment was performed as following. Cells were incubated with aromatic herbs for 3 h. The membrane fluidity were detected by FRAP. The changes of membrane potentials and the concentration of calcium ions were detected by flow cytometer.. Borneol (55.6, 111.2 microg/mL) and muscone (8.34, 16.68 microg/mL) significantly enhanced the cell membrane fluidity. Borneol (27.8, 55.6, 111.2 microg/mL) and muscone (4.17, 8.34, 16.68 microg/mL) made the MDCK and MDCK-MDR1 membrane potentials less negative or depolarized. Borneol increased the concentration of intracellular free calcium in MDCK while decreased the concentration of intracellular free calcium in MDCK-MDR1 cells. Muscone increased the concentration of calcium in MDCK and MDCK-MDR1 cells. Na+, K(+)-ATPase activity was significantly increased in borneol and muscone group.. The regulating effect of membrane fluidity, membrane potential, Na+, K(+)-ATPase activity and calcium ions in MDCK and MDCK-MDR1 cells might be one of the mechanisms of borneol and muscone's BBB opening function.

Topics: Animals; Biological Transport; Blood-Brain Barrier; Calcium; Camphanes; Cell Membrane; Cell Membrane Permeability; Cycloparaffins; Dogs; Dose-Response Relationship, Drug; Drug Interactions; Iridoids; Madin Darby Canine Kidney Cells; Membrane Potentials; Models, Biological; Sodium-Potassium-Exchanging ATPase

The objective of this study was (1) to characterize geniposide transport through MDCK and MDCK-MDR1 cell lines to confirm its transport mechanism and (2) to evaluate the effect of borneol and muscone as enhancers of geniposide transport in the BBB models so as to explore the enhancement mechanism. Transport studies of geniposide were performed in both directions, from apical to basolateral and from basolateral to apical sides. Drug concentrations were analyzed by HPLC. Geniposide showed relatively poor absorption in MDCK and MDCK-MDR1 cells, apparent permeability coefficients ranging from 0.323×10(-6) to 0.422×10(-6) cm/s. The in vitro experiments showed that geniposide transport in both directions was not concentration dependent and saturable, indicating purely passive diffusion. The efflux ratio of geniposide was less than 2 in the two cell models, which suggested that geniposide was not P-gp substrates. Geniposide transport in both directions significantly increased when co-administrated with increasing concentrations of borneol and muscone. Actin staining results indicated that borneol and muscone increased geniposide transport in the BBB models may attribute to disassembly effect on tight junction integrity.

Topics: Animals; Biological Transport; Blood-Brain Barrier; Camphanes; Cell Survival; Cycloparaffins; Dogs; Drug Delivery Systems; Iridoids; Madin Darby Canine Kidney Cells; Models, Biological