OBJECTIVETo observe the effect of natural borneol on the permeability of blood tumor barrier (BTB) model and the expression and activation of mitogen-activated protein kinase (MAPKs) signal transduction pathway related protein kinase in vitro.

METHODSC6 rat glioma cells and human umbilical vein endothelial cells (HUVECs) were co-cultured to establish BTB model. Then 4 groups were set up, the blank control group, low, middle, and high dose borneol groups (25, 50, 100 µg/mL), 3 samples collected at 7 time points (0, 10, 30, 60, 120, 180, 240 min, respectively). Blank culture medium was exchanged in the blank control group while medication. Different doses of natural borneol were administered to the 3 borneol groups. Cells were collected at different time points. BTB permeability was determined using horseradish peroxidase (HRP). Expression levels of extracellular signal regulated protein kinase (ERK), phosphorylation extracellular signal regulated protein kinase (P-ERK), P38MAPK, phosphor-P38MAPK, c-Jun N-terminal kinase (JNK), and phosphorylation c-Jun N-terminal kinase (P-JNK) were detected using Western blot.

RESULTSCompared with the same group at min 0, the permeation rate obviously increased (P < 0.01) in the 3 borneol groups at the rest time points. P-ERK expression was elevated first, reached the peak at 30 min, and gradually recovered to the initial level (P > 0.05). Compared with the blank control group, HRP permeation rate increased from 10 min to 240 min (P < 0.01), and expression of P-ERK protein increased at 30 min and 60 min (P < 0.05) in the low dose borneol group; expression of P-JNK protein decreased in the 3 borneol groups at 180 min and 240 min (P < 0.05). Compared with the low dose borneol group, expression of P-ERK protein increased from 10 min to 180 min (P < 0.05), HRP permeation rate increased from 30 min to 180 min (P < 0.05), expression of P-JNK protein decreased at 180 and 240 min (P < 0.05) in the middle dose borneol group. Compared with the middle dose borneol group, HRP permeation rate increased from 10 min to 180 min (P < 0.05), expression of P-ERK protein increased from 10 min to 180 min (P < 0.05), expression of P-JNK protein increased at 180 min and decreased at 240 min (both P < 0.05) in the high dose borneol group.

CONCLUSIONNatural borneol arrived at the effect of regulating reversible BTB patency possibly through activating phosphorylation of ERK in MAPKs signal transduction pathway, and further reversibly down-regulating expression of associated proteins.

Animals ; Bornanes ; pharmacology ; Cell Line, Tumor ; drug effects ; Coculture Techniques ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Glioma ; pathology ; Human Umbilical Vein Endothelial Cells ; Humans ; JNK Mitogen-Activated Protein Kinases ; metabolism ; Neoplasms ; pathology ; Permeability ; Phosphorylation ; Rats ; Signal Transduction ; drug effects ; p38 Mitogen-Activated Protein Kinases ; metabolism

Borneol is a traditional Chinese medicine. In the past few years, many studies showed that borneol can improve the bioavailability of other drugs, promoting drugs to cross the blood-brain barrier, so the potential drug interactions between borneol and other medicines have attracted great attention, but the influence of borneol to CYP450 and its isoforms are rarely reported. In this research, male Wistar rats were orally administered by borneol for 7 days, then the mRNA and protein expression and the activities of CYP2D were detected, we also compared the pharmacokinetic parameters of CYP2D's specific substrate between control group and borneol group. The results show that borneol (33, 100 and 300 mg x kg(-1) x d(-1)) have no significant effect on CYP2D, while the activites of CYP2D increased 1.71, 1.97 and 2.89 times comparing to the control group. At the same time, borneol (300 mg x kg(-1) x d(-1)) caused the C(max) decreased 10.6% (P > 0.05), AUC(0-∞) decreased 27.5% (P < 0.01), CL/F increased 41.1% (P < 0.01), V(z)/F increased 23.1% (P > 0.05) of dextromethorphan. Our data provided that borneol speed up dextromethorphan's elimination in vivo. Since the activity of CYP2D can be induced by borneol, the metabolic interactions might happen when borneol and the substrate drug CYP2D are used together.
Animals ; Aryl Hydrocarbon Hydroxylases ; metabolism ; Blood-Brain Barrier ; Bornanes ; pharmacology ; Cytochrome P-450 Enzyme Inducers ; pharmacology ; Dextromethorphan ; Drug Interactions ; Liver ; drug effects ; enzymology ; Male ; Medicine, Chinese Traditional ; RNA, Messenger ; Rats ; Rats, Wistar

The borneol was included with β-CD and prepared Fufang Danshen intestinal adhesion pellets. GC method for determination of borneol in Fufang Danshen intestinal adhesion pellets was established to study its in vitro dissolution and make a comparison with the Fufang Danshen tablet, in this way, the rationality of dosage form was evaluated. The first method of dissolution determination was used for determining the in vitro dissolution of borneol in Fufang Danshen intestinal adhesion pellets in artificial intestinal juice, and Fufang Danshen tablet in artificial gastric juice and intestinal juice, respectively. Result shows: the concentration of borneol in Fufang Danshen intestinal adhesion pellets and Fufang Danshen tablet was 0.79% and 0.80%, respectively. Its in vitro dissolution was nearly 70% within 12 h in Fufang Danshen intestinal adhesion pellets, and in Fufang Danshen tablet, the dissolution was about 60% within 20 min and more than 90% within 40 min, and in artificial gastric juice, was less than 20% within 40 min but more than 80% till 150 min. Research suggests that in comparison with Fufang Danshen tablet, in vitro dissolution of borneol in the Fufang Danshen intestinal adhesion pellets showed an obvious sustained release behavior. The borneol in Fufang Danshen intestinal adhesion pellets was included with β-CD and prepared enteric preparations. To some extent, the stimulation on stomach and intestinal mucosa can be reduced and safety can be improved.
Bornanes ; adverse effects ; chemistry ; pharmacology ; Chemistry, Pharmaceutical ; methods ; Dosage Forms ; Drugs, Chinese Herbal ; adverse effects ; chemistry ; pharmacology ; Humans ; Intestinal Mucosa ; drug effects ; metabolism ; Models, Biological ; Solubility

Borneol is a major component of many medicinal plant essential oils, as well as a popular traditional Chinese medicine. This essay collects the results of the latest domestic and foreign studies, and summarizes and analyzes its activity and reaction mechanism on analgesia, putridity elimination and flesh regeneration, and repair of damaged cells. Moreover, it proposes problems concerning borneol during medical studies, providing support for the in-depth study and exploration of efficacies of precious traditional Chinese medicines as well as the effective utilization and development of innovative medicines.
Animals ; Bornanes ; adverse effects ; metabolism ; pharmacokinetics ; pharmacology ; Humans ; Medicine, Chinese Traditional ; Safety

Malignant tumor, epilepsy, dementia, cerebral ischemia and other brain diseases have very high rates of disability and mortality. Currently, many drugs are developed to treat such diseases and the effect is obviously. But they can not achieve the purpose to control these diseases because many of the drugs can not pass through the blood-brain barrier (BBB). Therefore, the treatment is not good. Borneol as the represent of the aromatic resuscitation medicine, it has strong fat-soluble active ingredients, small molecular weight, volatile and through the BBB quickly. It can also promote other therapeutic drugs through the BBB. It has two-ways regulations on BBB permeability and the damage of brain tissue is small, this have important theoretical significances and application values.
Animals ; Biological Transport ; drug effects ; Blood-Brain Barrier ; drug effects ; metabolism ; Bornanes ; pharmacology ; Brain ; drug effects ; metabolism ; Humans

OBJECTIVETo explore the influence of borneol on intestinal absorption of muscone in rats.

METHODAn in situ intestinal circulation perfusion experiment was used to study the changes in intestinal absorption kinetics of muscone before and after being compatible with borneol.

RESULTCompared with the muscone group (MG), the absorption rate constants (Ka), the half-life period (T1/2) and the absorption rate (A) of muscone in the borneol + muscone group (BMG) were on the rise, but with no significant difference; after being compatible with borneol for a long period, Ka, T1/2 and A in the last borneol on muscone group (LBMG) increased, with significant difference (P < 0.05). in duodenum, LBMG showed better effects than MG (T1/2, P < 0.05); and so did in jejunum (Ka, P < 0.05; T1/2, P < 0.05); in ileum, there was no significant statistical difference between LBMG and MG.

CONCLUSIONBorneol can promote the intestinal absorption of muscone in rats to some extent.

Animals ; Bornanes ; pharmacology ; Cycloparaffins ; pharmacokinetics ; Drug Interactions ; Drugs, Chinese Herbal ; pharmacokinetics ; pharmacology ; Intestinal Absorption ; drug effects ; Intestines ; drug effects ; metabolism ; Male ; Rats ; Rats, Wistar

OBJECTIVETo research the effects of moschus, borneol, styrax and benzoinum on the structure and function of blood brain barrier in cerebral ischemia-reperfusion injury model rats.

METHODFocal middle cerebral artery occlusion (MCAO) was introduced as an in vivo ischemic model in rats. After 2 h MCAO, nylon suture was pulled up 1 cm to give blood reperfusion. After 22 h reperfusion, all animals were decapitated. The ultramicrostructure of blood brain barrier of ischemia hemisphere side in fronto-parietal cortex region by transmission electron microscope, and the content of VEGF and MMP-9 in ischemia side brain tissue were measured by ELISA.

RESULTIn model and solvent group rats, the capillary endothelium cells, astro-glial cells and nerve cells in ischemia hemisphere side in fronto-parietal region were emerged in different degree compared with sham-operated groups, which exhibited tight junction between endothelial cells being opened, basal lamina being dissolved, and permeability increasing, and cellularedema. In borneol (0.2 g x kg(-1)) group rats, the structure of three kinds of cells were nearly normal, which tight junction structure was clear, rough endoplasmic reticulum and polyribosome could be found in cytoplasm. In moschus (66.6 mg x kg(-1)) group rats, the structure of capillary endothelium cells and astrocytes were nearly normal as well as the basal lamina, but the electrons in neurons was maldistribution. In styrax (1.332 g x kg(-1)) group rats, astrocytes were nearly normal, while capillary endothelial cells and neurons exhibited oedema in different degrees. And the basal lamina was discontinuous, augmentation of cell spaces in endothelial cells increased the permeability, some endoplasmic reticulum broadened and ribosome ablated. In benzoinum (1.0 g x kg(-1)) group rats, oedema of capillary endothelial cells and astrocytes was significant, basal lamina broke. Meanwhile endoplasmic reticulum broadened as vacuole, the number of ribosome in rough endoplasmic reticulum decreased, crista mitochondriales in some neurons disappeared as vacuole which hint oedema happened. Results also showed that borneol decrease the level of VEGF in ischemia side brain tissue significantly, while has little influence on the level of MMP-9. Moschus showed the tendency to decrease the level of VEGF and MMP-9 in ischemia side brain tissue.

CONCLUSIONAromatic resuscitation drugs showed the protection effect on blood brain barrier in cerebral ischemia-reperfusion injury rats, which the protection effect of moschus and borneol were better than that of styrax and benzoinum. The mechanism of protection effect maybe related to decrease the level of VEGF and MMP-9.

Animals ; Benzoin ; pharmacology ; Blood-Brain Barrier ; drug effects ; metabolism ; ultrastructure ; Bornanes ; pharmacology ; Brain Ischemia ; drug therapy ; metabolism ; Disease Models, Animal ; Fatty Acids, Monounsaturated ; pharmacology ; Infarction, Middle Cerebral Artery ; drug therapy ; metabolism ; Male ; Matrix Metalloproteinase 9 ; drug effects ; metabolism ; Neuroprotective Agents ; pharmacology ; Plant Extracts ; pharmacology ; Rats ; Reperfusion Injury ; drug therapy ; metabolism ; Styrax ; chemistry ; Vascular Endothelial Growth Factor A ; drug effects ; metabolism

This study aimed to investigate the effects of concentration, intestinal section and borneol on the intestinal absorption of salvianolic acids. The experiment not only studied the intestinal absorption properties of three concentrations of rosmarinic acid, salvianolic acid B and salvianolic acid A at duodenum, jejunum and ileum, but also of salvianolic acids compatible with borneol at different concentrations using single-pass intestinal perfusion model in rat with phenol red as the marker. The results showed that salvianolic acids was stable under weak-acid condition and affected by metabolism enzyme; The Peff and Ka significantly different among three concentrations of rosmarinic acid and salvianolic acid B, whose intestinal absorption were saturated in high concentration, suggesting that the transport mechanisms of rosmarinic acid and salvianolic acid B were similar to active transport or facilitated diffusion; However, there was inconspicuousness in the Peff and Ka of salvianolic acid A at different concentrations, whose absorption was not saturated in high concentration, indicating that the transport mechanisms of salvianolic acid A was passive diffusion; The Peff and Ka in the ileum obviously higher than those in the duodenum and jejunum, namely the ileum was the best absorption section; When concentration of borneol increased, the enhancing effect of intestinal absorption of salvianolic acids increased, but significantly decreased when borneol increased to some degree. The enhancing effect of medium borneol concentration was the optimum. This implied that borneol can enhance the intestinal absorption of salvianolic acids, and the capacity of enhancing effect was influenced by the concentration of borneol.
Animals ; Benzofurans ; isolation & purification ; pharmacokinetics ; Bornanes ; administration & dosage ; pharmacokinetics ; pharmacology ; Caffeic Acids ; isolation & purification ; pharmacokinetics ; Cinnamates ; isolation & purification ; pharmacokinetics ; Depsides ; isolation & purification ; pharmacokinetics ; Dose-Response Relationship, Drug ; Duodenum ; metabolism ; Ileum ; metabolism ; Intestinal Absorption ; Jejunum ; metabolism ; Lactates ; isolation & purification ; pharmacokinetics ; Male ; Perfusion ; methods ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Salvia miltiorrhiza ; chemistry

OBJECTIVETo observe the influence of borneol, a traditional Chinese medicine, on the concentration of ceftriaxone in the rat brain striatum and evaluate the relativity.

METHODThe sample of cerebrospinal fluid in the rat brain striatum was collected via brain microdialysis technology, and then the contents of ceftriaxone in standard preparation and sample were detected by high efficiency liquid chromatography combined with diode array detector respectively and analyzed statistically. The concentration of ceftriaxone in rat brain striatum in the ceftriaxone + Borneol group was compared with that in the ceftriaxone-only group.

RESULTThe concentration of ceftriaxone in the rat brain in the ceftriaxone + Borneol group (13.01-4.43 mg x L(-1)) is significantly higher than that in the ceftriaxone-only group (2.41-0.94 mg x L(-1)).

CONCLUSIONBorneol can promote ceftriaxone through blood-brain barrier, and increase the concentration thereof in striatum.

2-Pyridinylmethylsulfinylbenzimidazoles ; pharmacokinetics ; Animals ; Blood-Brain Barrier ; Bornanes ; pharmacology ; Ceftriaxone ; pharmacology ; Chromatography, High Pressure Liquid ; Corpus Striatum ; drug effects ; metabolism ; Drug Combinations ; Male ; Medicine, Chinese Traditional ; Microdialysis ; Neostriatum ; drug effects ; metabolism ; Rats ; Rats, Wistar

OBJECTIVETo observe the influence of natural borneol and synthetic borneol on mucosal permeability of Gardenia extract.

METHODTaken frog skin as a vitro model to study the vitro mucosal permeation the impacts of the natural borneols and synthetic borneols on the P(app) of the Jasminoidin were studied, and the effect of different borneols on the stability of Jasminoidin were investigated. Compared the 10 h accumulated infiltration rate of each group the effects of influence factors,such as C(Ge), C(B) and rotation speed on P(app) were investigated by using response surface method.

RESULTThe P(app) of Jasminoidin of natural borneol and synthetic borneol group were 1.44 fold and 1.77 fold of control group (P < 0.01). For two borneol groups, the results also showed a significant difference too (P < 0.05). Jasminoidin began to degrade about 8 h after the effect of frog skin for control group and synthetic borneol group, but was stable within 12 h for natural borneol group. The accumulated permeation rate of 10 h was same for different borneol groups. It was about 1.3 fold of control group. The C(Ge) had a salinence influence on the P(app) (P < 0.01) and C(B) had a salience influence on time-lag (P < 0.01).

CONCLUSIONBoth the natural borneol and synthetic borneol can accelerate the permeation of Jasminoidin and the synthetic borneol has stronger effect on the P(app). Both two different borneol can reduce the degradation effect of frog skin to Jasminoidin, but the natural borneol has a better protect effect on it. By using more natural borneol, the mucosal permeability of Gardenia extract can be increased, the time-lag can be reduced, and Jasminoidin has better stability.

Administration, Cutaneous ; Bornanes ; chemical synthesis ; pharmacokinetics ; Dosage Forms ; Drugs, Chinese Herbal ; chemistry ; Gardenia ; chemistry ; Iridoids ; pharmacology ; Mucous Membrane ; metabolism ; Nasal Mucosa ; metabolism ; Permeability ; Skin ; metabolism ; Skin Absorption