Effect Of Borneol Research Articles

Progress in Proteomic Mass Spectrometry Studies on the Effects of Borneol and Menthol as Enhancers on Corneal Injury Repair

Cornea transparent, avascular tissue, is an important part of the refractive function. Corneal injury is the destruction of the corneal structure caused by blunt eyeball, external force, high pressure gas or fluid hitting the cornea. Common in boxing injury, ball injury, stone injury, head collision, etc. The external force directly acts on the formation of the cornea, mainly manifested as vision loss, pain, photophobia, tears, ciliary congestion and contusion corneal edema. Mild corneal damage can be restored under the strong self-healing ability of the corneal epithelium. If serious corneal damage, the corneal stromal layer will leave a scar on the cornea to affect the vision, but also likely to cause related complications, and even lead to complete blindness. Recent studies have shown that corneal alkali burn is one of the most common eye injuries. Due to the strong corrosion of alkaline substances, it can cause degeneration and dissolution of corneal tissue proteins. The lipophilic properties of alkaline substances make it difficult to limit the damage site and easy to form ulcers. In this paper, we discuss the borneol and menthol on the corneal damage repair mass spectrometry, through the influence of borneol and menthol on corneal damage repair and the preliminary test of ice and menthol can be used, in order to provide a new clinical treatment of corneal damage to the new research direction.

Effect of borneol as a penetration enhancer on brain targeting of nanoliposomes: facilitate direct delivery to neurons.

This study is aimed to evaluate borneol as a penetration enhancer to improve brain target of nanoliposome. Effects of borneol on pharmacokinetics, targeting efficiency, brain subareas distribution and neuron-targeting level and pathway were studied by fluorescence spectrophotometry and immunofluorescence. Borneol did not influence physicochemical property of doxorubicin hydrochloride nanoliposome (Dox-nanoLips). Co-administration of Dox-nanoLips with borneol elevated brain-target efficiency due to selective distribution increase in the cerebral cortex and hippocampus without difference in contralateral hemisphere. Borneol improved neuronal-targeting level of Dox-nanoLips in the cortex, CA3 and dentate gyrus regions via opening tight junctions of blood-brain barrier and then bypassing astrocyte. Borneol is potential to be a promising penetration enhancer for nanocarrier to target neurons.

Borneol and Α-asarone as adjuvant agents for improving blood–brain barrier permeability of puerarin and tetramethylpyrazine by activating adenosine receptors

Puerarin (PUE) and tetramethylpyrazine (TMP) are central nervous system (CNS) drugs used in cerebrovascular diseases. Poor brain–blood barrier (BBB) permeability limited their clinical application. Borneol and α-asarone have been proposed as an oral brain-targeting enhancer. In this study, we aimed to first evaluate the ‘orifice-opening’ effect of borneol and α-asarone, both aromatic resuscitation drugs, on improvement of brain delivery of PUE and TMP and second to investigate whether the enhancing effects were associated with adenosine receptors (ARs)-mediated trans-BBB pathway. In vitro BBB model was established and borneol and α-asarone significantly increased the cumulative amount of permeated PUE and TMP and the enhancing effects could be counteracted by AR inhibitors. Borneol and α-asarone could decrease expression of ZO-1, an important BBB junction protein, but inversely increase the expression of A1AR and A2AAR. In vivo pharmacokinetic study also confirmed that oral co-administration of borneol or α-asarone significantly increased AUCbrain for PUE and TMP. These results suggested that borneol and α-asarone are both effective adjuvant agents for delivery of PUE and TMP to the brain.

Effect factors and mechanisms of borneol's bidirectional regulation on blood-brain barrier permeability

In recent twenty years, there are a lot of studies about the effect of borneol on permeability of blood-brain barrier(BBB); however, it isDODOrt of regular conclusions of effect factors and in-depth analysis of functional mechanisms. The current researching data were collected and analyzed in this paper for illuminating the effect factors and mechanisms of borneol on permeability of BBB.The following conclusions were obtained: five factors about borneol influencing the permeability of BBB. First, opticity activity of borneol had no significant effect on action effects. Second, dose of borneol in the range of 50.00-200.00 mg•kg⁻¹, did not affect the effect direction, but only affect its action intensity either with use alone or combination use. Third, the borneol can increase the permeability of physiological BBB, and decrease the permeability of pathological BBB. Fourth, regardless of using singly or using compatibility with musk, borneol can decrease the permeability of BBB in different brain disease models. Fifth, when used with astragalus, catalpol or puerarin, borneol can increase the permeability of BBB and promote the drugs through BBB in pathological conditions. The target spots and mechanisms of borneol's bidirectional regulation on the permeability of BBB are related to the structure and function of cerebral endothelial cells, the exocytosis effects of P-gp and low pinocytosis internal transport effects. On one hand，borneol can down-regulate P-gp by inhibiting NF-κB to reduce the exocytosis effects of P-gp and promote the blood brain barrier pinocytosis to increase the permeability of BBB; On the other hand，borneol can reduce the degradation of basement membrane of blood vessel and tight junctions by inhibiting the expression of IL-1β, MMP-9 to decrease the permeability of BBB；moreover，borneol has bidirectional regulation effects on blood-brain barrier permeability by influencing the signaling pathways of Ca2+-eNOS-NO, VEGF-eNOS-NO. However, the detailed mechanisms that borneol regulates and controls the permeability of BBB are so complicated, so they shall be further proved and clarified.

Simultaneous determination of seven alkaloids from Rhizoma Corydalis Decumbentis in rabbit aqueous humor by LC-MS/MS: Application to ocular pharmacokinetic studies.

This study aims to establish a fast and sensitive LC-MS/MS method for simultaneous determination of seven alkaloids from Rhizoma Corydalis Decumbentis in rabbit aqueous humor. Aqueous humor samples were processed by protein precipitation and then separated on a Thermo Syncronis C18 column (50mm×2.1mm, 5μm) with a mobile phase using acetonitrile-0.05% formic acid (28:72, v/v). Detection of the analytes and the internal standard (coptisine) were performed in positive electrospray ionization with selected reaction monitoring. The method showed good linearity (r>0.9931) for all the seven alkaloids. This fully validated method was applied to the studies of aqueous humor pharmacokinetics of seven alkaloids from Rhizoma Corydalis Decumbentis and the effects of borneol on corneal penetration of these alkaloids into aqueous humor. This is the first work that presents a reliable LC-MS/MS method for simultaneous determination of seven alkaloids in rabbit aqueous humor and its application of ocular pharmacokinetics of seven alkaloids from Rhizoma Corydalis Decumbentis.

Preventive Potential Of Borneol In Ischemic Stroke

Borneol is a bicyclic organic compound found in several species of Artemisia, Dipterocarpaceae and etc. It can easily permeate through the blood brain barrier and acts directly in neurons. Ischemic stroke, an imbalance of the blood supply to the brain because of blood clots, is a severe condition with high mortality and morbidity that represents 87% of all stroke cases. The aim of this study is to evaluate the effect of borneol in the prevention of stroke.Borneol can be synthesized by reduction of camphor by the Meerwein–Ponndorf–Verley reduction. Protection against Oxygen-Glucose Deprivation/Reperfusion Injury in Cortical Neurons by anti-oxidation and anti-inflammation through nuclear transcription factor κappaB signaling pathway is one of suggested mechanisms for borneol. Combination of some compounds and borneol can have a synergistic effect on treating ischemic stroke in a rat model. Also borneol permeating can increased into brain in the pathological state of stroke. This review was made to help better understanding of the borneol evaluation in ischemic stroke prevention.

Effects of Concentrations on the Transdermal Permeation Enhancing Mechanisms of Borneol: A Coarse-Grained Molecular Dynamics Simulation on Mixed-Bilayer Membranes.

Borneol is a natural permeation enhancer that is effective in drugs used in traditional clinical practices as well as in modern scientific research. However, its molecular mechanism is not fully understood. In this study, a mixed coarse-grained model of stratum corneum (SC) lipid bilayer comprised of Ceramide-N-sphingosine (CER NS) 24:0, cholesterol (CHOL) and free fatty acids (FFA) 24:0 (2:2:1) was used to examine the permeation enhancing mechanism of borneol on the model drug osthole. We found two different mechanisms that were dependent on concentrations levels of borneol. At low concentrations, the lipid system maintained a bilayer structure. The addition of borneol made the lipid bilayer loosen and improved drug permeation. The “pull” effect of borneol also improved drug permeation. However, for a strongly hydrophobic drug like osthole, the permeation enhancement of borneol was limited. When most borneol molecules permeated into bilayers and were located at the hydrophobic tail region, the spatial competition effect inhibited drug molecules from permeating deeper into the bilayer. At high concentrations, borneol led to the formation of water pores and long-lived reversed micelles. This improved the permeation of osthole and possibly other hydrophobic or hydrophilic drugs through the SC. Our simulation results were supported by Franz diffusion tests and transmission electron microscope (TEM) experiments.

Effects of borneol on the pharmacokinetics of 9-nitrocamptothecin encapsulated in PLGA nanoparticles with different size via oral administration

Context: Although nanocarriers provide promising potential for oral drug delivery, the delivery efficiency remains unsatisfactory and needs to be improved. Size is considered to be the most important characteristic of nanoparticles related to their oral absorption. Borneol has been proved to have the ability to enhance the penetration and transport of many drugs through various physical barriers.Objective: To investigate the effect of the particle size and coadministration of borneol on the pharmacokinetics and bioavailability of entrapped drug in different size poly(lactic-co-glycolic acid) (PLGA) nanoparticles.Materials and methods: 9-Nitrocamptothecin (9-NC)-loaded PLGA nanoparticles with three different range of size (50–100 nm, 100–200 nm, 200–300 nm) were prepared by emulsion solvent-evaporation method. The pharmacokinetic study in rats of these nanoparticles with borneol was carried out.Results: The experiments showed that the encapsulation drug in nanoparticles with size below 200 nm could improve the oral bioavailability of 9-NC. The small size nanoparticles (50–100 nm) had a better improvement efficacy. As for borneol, it played a significant promotion effect only on the small nanoparticles. Moreover, there was no significant influence on the nanoparticles with size more than 100 nm.Discussion and conclusion: The study indicated that both entrapping drug in nanoparticles with the size below 100 nm and coadministrating with borneol could enhance the gastrointestinal absorption of water insoluble drug. The combination of the two strategies provides a potential approach to improve the oral bioavailability of drug.

Xingnaojing mPEG2000-PLA modified microemulsion for transnasal delivery: pharmacokinetic and brain-targeting evaluation

Xingnaojing microemulsion (XNJ-M) administered intranasally is used for stroke treatment. In order to decrease the XNJ-M-induced mucosal irritation, XNJ-M modified by mPEG2000-PLA (XNJ-MM) were prepared in a previous work. The present work aimed to assess the impact of mPEG2000-PLA on pharmacokinetic features and brain-targeting ability of XNJ-M. The bioavailability and brain-target effects of borneol and geniposide in XNJ-M and XNJ-MM were compared in mice after intravenous (i.v.) and intranasal (i.n.) administrations. Gas chromatography, high-performance liquid chromatography, and ultra-performance liquid chromatography/tandem mass spectrometry methods were developed for the quantification of borneol and geniposide. Blood and brain samples were collected from mice at different time points after i.v. and i.n. treatments with borneol at 8.0 mg/kg, geniposide at 4.12 mg/kg. In addition, near-infrared fluorescence dye, 1,1′-dioctadecyl-3,3,3′,3′-tetramethyl indotricarbocyanine iodide was loaded into microemulsions to evaluate the brain-targeting ability of XNJ-M and XNJ-MM by near-infrared fluorescence imaging in vivo and ex vivo. For XNJ-M and XNJ-MM, the relative brain targeted coefficients (Re) were 134.59% and 198.09% (borneol), 89.70% and 188.33% (geniposide), respectively. Besides, significant near-infrared fluorescent signal was detected in the brain after i.n. administration of microemulsions, compared with that of groups for i.v. administration. These findings indicated that mPEG2000-PLA modified microemulsion improved drug entry into blood and brain compared with normal microemulsion: the introduction of mPEG2000-PLA in microemulsion resulted in brain-targeting enhancement of both fat-soluble and water-soluble drugs. These findings provide a basis for the significance of mPEG2000-PLA addition in microemulsion, defining its effects on the drugs in microemulsion.

Improved blood–brain barrier distribution: Effect of borneol on the brain pharmacokinetics of kaempferol in rats by in vivo microdialysis sampling

Ethnopharmacological relevanceKaempferol (KA) exists in a variety of herbal medicines. In vitro and in vivo studies have focused on the anti-Alzheimer effect of KA. However, little is known about its brain pharmacokinetic profile. The accumulated amount of KA in brain is very low because of the protection of blood–brain barrier (BBB). Borneol (BO) is a classical aromatic refreshing traditional Chinese medicine and commonly used as an adjuvant component of traditional Chinese medicines (e.g. compound Danshen dropping pills) in the treatment of cardiovascular and cerebrovascular diseases. According to the basic theories of traditional Chinese medicine, BO is called an “upper guiding drug”, which can guide other components to the targeting tissues or organs in the upper part of the body, especially in the brain. Materials and methodsThe probes for blood and brain sampling were implanted within the jugular vein/right atrium and right hippocampus of SD rats, respectively. Rats were intravenous administered of KA (25mg/kg) alone or combined with BO (15, 30mg/kg) via caudal vein. The blood and brain microdialysates were collected every 15min for 180min and every 30min for 180−300min. A selective and sensitive high performance liquid chromatography–chemiluminescence method was developed for the determination of unbound KA in rat blood and brain microdialysates, which can be converted to their actual free-form concentrations based on the in vivo relative recoveries of KA across microdialysis probes. ResultsKA quickly crossed the BBB to enter the extracellular fluid of hippocampus and reached the maximum concentration of 0.11μg/mL within 30min. The brain bioavailability and brain delivery of KA evidently increased with the co-administration of 15 and 30mg/kg of BO. The AUC0–inf of KA in brain increased 1.84 and 2.19 times, and the Cmax of KA in brain increased 2.09 and 3.18 times than that without BO, respectively. In addition, the brain-to-blood distribution ratio of KA increased by 48.68% and 57.97% compared with that without BO. However, no significant difference in the T1/2 of unbound KA in blood aserved between three groups. ConclusionsBO can enhance the BBB permeability and improve the transportation of KA to brain. The dose-dependent effect of BO on the brain pharmacokinetic parameters of KA was observed. This co-administration strategy can be designed to enhance the brain accumulation of other neuropsychiatric medications.

The effect of borneol on the concentration of meropenem in rat brain and blood

Meropenem is a carbapenem antibiotic with a wide spectrum of activity against both Gram-positive and Gram-negative bacteria. Because of its clinical efficacy, meropenem is an excellent choice for the treatment of serious infections in both adults and children. The knowledge of tissue concentrations of antibiotic in an infection site is valuable for the prediction of treatment outcome. The aim of the present study is to investigate the effect of borneol on the concentration of meropenem in rat brain and blood and to find the potential relationships of the combined use of medicine and traditional Chinese medicine. Analysis of meropenem in the dialysates was achieved using the microdialysis technique and HPLC. At 40 min after the administration of an intraperitoneal injection of meropenem, the concentration of meropenem in brain in borneol+meropenem group was 2.25 (0.35) μg ml− 1, which was significantly higher than that in meropenem group [1.20 (0.12) μg ml− 1; P < 0.01]. Within 80 min of drug administration, the AUCbrain/AUCblood (area under the curve, AUC) in the borneol+meropenem group was 1.2 times that of the meropenem group. Borneol can increase the concentration of meropenem in the cerebrospinal fluid, but has no influence on its blood concentration. This study represents a successful application of the microdialysis technique, which is an effective method for the study of pharmacokinetics of meropenem.

The mechanism of the opening of the blood–brain barrier by borneol: A pharmacodynamics and pharmacokinetics combination study

Ethnopharmacological relevanceBorneol is widely used in traditional Chinese medicine to facilitate the distribution of central nervous system (CNS) drugs in brain due to its ability to open blood–brain barrier (BBB), however, the underlying mechanism is still unclear. In this study, the effect of borneol on different brain regions were investigated to explore the mechanism. Materials and methodsAfter oral administration of borneol (0.1, 0.2g/kg) for seven consecutive days, SD rats were injected with Rh123 (1.0mg/kg). The concentrations of Rh123 were detected in four brain regions of cortex, hippocampus, hypothalamus and striatum by a small animal vivo imaging system and a fluorescence microplate reader respectively. The ultrastructures of BBB were examined. Moreover, the expressions of the four transporters of ATP-binding cassette (ABC) family, multidrug resistance 1a (Mdr1a), multidrug resistance 1b (Mdr1b), multidrug resistance protein 1 (Mrp1), Mrp4, Mrp5 and breast cancer resistance protein (Bcrp) in the four brain regions were analyzed. Finally, the deliveries of borneol in the plasma and the four brain regions were examined by a pharmacokinetics study. ResultsAdministration of 0.2g/kg borneol produced loose structure in the tight junction and void structure between the endothelial cell and mesangial cell. Borneol at 0.1g/kg and 0.2g/kg increased the delivery of Rh123 in hippocampus and hypothalamus obviously. Permeability index followed a similar trend. Protein expression assays showed that borneol decreased the expression of Mdr1 and Mrp1 in hippocampus and hypothalamus. Further RT-PCR study showed that borneol decreased the expressions of both Mdr1a and Mdr1b in hippocampus and hypothalamus. The pharmacokinetics study demonstrated that the delivery of borneol in cortex was the most and that in striatum the least, with the deliveries of borneol in hippocampus and hypothalamus in between. ConclusionsBorneol showed tissue specific BBB-opening effect, which was associated with its regulation of the ultrastructure of brain tissues and the expressions of Mdr1a, Mdr1b and Mrp1. The present study indicated that borneol should be used in concert with drugs targeting hippocampus or hypothalamus to exert its synergistic effect to the maximum.

Effect of borneol on cytochrome P450 3A enzyme and midazolam pharmacokinetics in rats

Borneol is a commonly used herbal medication in China and Japan. Previous studies have indicated that borneol could reduce the plasma concentrations of oneself and concomitant drugs, and its first-pass metabolism could be catalyzed by the cytochrome P450 3A (CYP3A) enzyme as well. The impact of borneol on CYP3A activity and efficacy in influencing the pharmacokinetics of co-administrated drugs is currently unknown. Therefore, the purpose of the current study is to investigate the effect of borneol on CYP3A enzyme in vivo. After treatment with borneol twice daily for 3days, rat liver microsomes were exposed to probe substrates to determine CYP3A enzyme activity, protein, and RNA harvested using microsomal testosterone 6β-hydroxylation as a marker of enzyme activity. To verify the result, the effect of borneol on the pharmacokinetics of the CYP3A model substrate midazolam was further examined. The results showed that borneol treatment had increased CYP3A expression at the mRNA, protein, and activity (testosterone 6β hydroxylase activity) level in rat liver microsomes. In addition, borneol accelerated the metabolism of midazolam, which was consistent with the enhancement in CYP3A metabolic capacity. The hepatic clearance (Cl) of midazolam injected via the caudal vein in rats following borneol co-administration was higher; however, the area under the curve (AUC0-∞) was lower than the solvent. Hence, it was proposed that borneol could increase the metabolic activity of the CYP3A enzyme, which might cause drug-drug interactions in humans when using Chinese herbal or Western medicine with borneol.

Effects of borneol on the pharmacokinetics of geniposide in cortex, hippocampus, hypothalamus and striatum of conscious rat by simultaneous brain microdialysis coupled with UPLC–MS

It has been verified that borneol could promote the accumulation of other drugs in the whole brain. In this study, a microdialysis sampling system coupled with UPLC–MS was developed to evaluate the delivery of geniposide to four brain regions (cortex, hippocampus, hypothalamus and striatum) of conscious rats in the absence/presence of borneol: rats were administrated with geniposide alone (300mg/kg, iv) or administrated with both geniposide and borneol (0.2g/kg, ig). The dialysate collected from specific brain area was analyzed by a UPLC–MS system: separated on a BEH C18 column (50mm×2.1mm id, 1.7μm) within 1.5min, and detected in positive ion electrospray mode. The calibration curve was in good linearity over the concentration range of 0.009–90μg/mL. The inter- and intra-day accuracies were within ±10%, and the precisions were within 9.13%. The established method was applied to study the brain pharmacokinetics of geniposide and the results demonstrated that borneol markedly facilitated the delivery of geniposide to hippocampus and hypothalamus, but slightly hampered its delivery in cortex.

Enhancing effects of different dosages of borneol on pharmacokinetics of salvanic acid B after oral administration to rats

The main purpose of this study was to illustrate the effect of borneol on pharmacokinetics of salvianolic acid B (SalB) in rats after oral administration of SalB with different doses of borneol. The concentrations of SalB in rat plasma were determined by an established and validated LC-MS/MS method. Our data showed that when 20, 40, and 80 mg kg− 1 of borneol were orally administrated with SalB at 50 mg kg− 1, C max of SalB was increased by 18.4%, 55.8%, and 103.2% compared with that of SalB alone. And AUC0 − t of SalB in plasma was increased by 14.4%, 48.5%, and 123.3%, respectively. The results indicated that borneol is able to enhance the intestinal absorption and relative bioavailability of SalB, with a positive dose-dependent relationship. The described herb–drug interactions might prove the scientific rationality of the compatible ratio of traditional Chinese medicines.

Oral characteristics of bergenin and the effect of absorption enhancers in situ, in vitro and in vivo

The purpose of this study was to explore the absorption characteristics of bergenin (CAS 477-90-7) and to improve its bioavailability by modulation of the gastrointestinal (GI) absorption using two enhancers (borneol and Poloxamer 188, resp. F68) based on in situ absorption model, in vitro Caco-2 monolayer and in vivo pharmacokinetics studies and comparing the results obtained. The effect of borneol and F68 on drug absorption was quantified at two concentration levels (1 or 4 mg/ml). The observations from in situ and in vitro model indicated that the oral absorption of bergenin is limited and passive diffusion could be the main manner. After oral administration alone (60 mg/kg), a biphasic characteristic was observed. AUC0-->infinity was only 1.95 +/- 0.29 microg x h/ml and Cmax was 0.44 +/- 0.11 microg/ml. From the results of in situ experiments, both of the enhancers were able to increase the absorption percentage of bergenin. Significantly increased (P < 0.05) apparent permeability was observed in Caco-2 cell monolayer. The oral bioavailability of bergenin in rats was improved in the presence of borneol or F68. AUC0-->infinity increased significantly (P < 0.05) to 8.61 +/- 3.74 and 3.41 +/- 1.17 microg x h/ml, which were 4.42 and 1.75-fold higher with borneol and F68 than that of the control group, respectively. The enhanced bioavailability suggests that borneol and F68 could promote the absorption of bergenin in the GI tract.

Effect of Borneol on the Distribution of Danshensu to the Eye in Rabbit via Oral Administration

Purpose: Both borneol and danshensu are bioactive substances derived from traditional Chinese medicine. In this paper, the effect of borneol on the distribution of danshensu to the eyes in rabbits via oral administration was investigated.Methods: The rabbits were injected danshensu (1.0 g/kg) into the auris dextra vein 15 min after intragastric administration of borneol and the danshensu concentrations in plasma, aqueous humor, and vitreous humor were measured by high-performance liquid chromatography. Draize test was used to examine the eye irritation.Results: Compared with the administration of danshensu alone, danshensu concentrations co-administrated with borneol in plasma were between 60.99 and 722.90 μg/ml. Peak times (Tmax) in both groups appeared at 0 min; however, compared with the control group, the values were not statistically significant although they differ (P > 0.05). The concentrations of danshensu in aqueous humor and vitreous humor in test group are higher than that in control group. The difference was statistically significant (P < 0.05). Tmax in both groups appeared at 25 min. Neither irritation nor inflammatory reaction was found during the examinations.Conclusion: The results suggest that the promoting effect of borneol on the permeability of drugs through the blood–ocular barrier in vivo is obvious, which indicates that borneol has the potential to be used as an ocular penetration enhancer.

LC Determination of the Intestinal Absorption of Etoposide in Vitro and in Rat Plasma

Etoposide (VP16), an anti-neoplastic agent, exhibits low and variable bioavailability. We have developed and validated a rapid, sensitive, and accurate LC–UV method for the determination of VP16 in vitro and in rat plasma after oral administration. The method was then used to investigate the absorption characteristics of VP16 with an in vitro diffusion chamber system across isolated rat intestinal membranes as a model. Borneol and eugenol were used to enhance the intestinal absorption of VP16. We also examined the effect of borneol and eugenol on the intestinal absorption of VP16 in vivo. The results showed that the plasma concentration of VP16 was significantly increased; relative bioavailability was 2.2-fold and 2.9-fold enhancement in the presence of borneol and eugenol, respectively, compared to VP16 administered alone.

Pharmacokinetic interaction between puerarin and edaravone, and effect of borneol on the brain distribution kinetics of puerarin in rats

The aim was to investigate the pharmacokinetic interaction between puerarin and edaravone, and the effect of borneol on the brain distribution kinetics of puerarin in rats. A reversed-phase high performance liquid chromatography method was developed and validated for the simultaneous determination of puerarin and edaravone in rat plasma. The detection method was successfully applied to compare the pharmacokinetic interaction and brain distribution kinetics of puerarin and edaravone using in-situ microdialysis sampling in rats after intravenous administration and co-administration with a single dose. The method gave good linearity and no endogenous material interfered with the two target compounds and internal standard peaks. The limit of detection of puerarin and edaravone was 0.03 and 0.05 microg/ml, respectively. The average recovery of the two compounds from rat plasma was >94%. The precision of the test was determined to be within 10%. The combination of puerarin and edaravone reduced drug elimination rates, gave a wider distribution, and the disposition of both drugs in rats was optimized. The distribution of puerarin in brain tissues was significantly increased and its elimination was noticeably slower with borneol pretreatment. The results provide important information for the improved combined use of puerarin and edaravone with borneol pretreatment in clinical practice.

Influence of borneol on primary mice oral fibroblasts: a penetration enhancer may be used in oral submucous fibrosis

Borneol, a widely used food and cosmetics additive, has analgesic, anti-inflammatory, antibacterial and penetration enhancing effects. We try to use it as a penetration enhancer for a formula which we have used to treat oral submucous fibrosis (OSF). To assess its safety, we investigate its effects on primary mice oral fibroblasts. Primary mice oral fibroblasts were cultured, the effects of borneol on fibroblasts proliferation, cytotoxicity, collagen production, matrix metalloproteinases-2,9 (MMP-2,9) activities and tissue inhibitors of metalloproteinase 1 (TIMP-1) production were tested by methyl thiazolyl tetrazolium assay, lactic dehydrogenase activity assay, chloramine T method, gelatin zymography and enzyme-linked immunosorbent assay, respectively. Borneol, from 18.75 to 300 microg/ml, could significantly (P < 0.05) decrease the growth of fibroblasts and very significantly (P < 0.01) inhibit collagen production in a concentration dependant manner. From 18.75 to 150 microg/ml, borneol had no cytotoxicity on mice oral fibroblasts. Moreover borneol could significantly (P < 0.05) decrease MMP-2 activity, and very significantly (P < 0.01) inhibit TIMP-1 production. This study indicates that borneol has anti-fibrosis activity and the mechanism may partly be relevant to its inhibiting effects on fibroblasts mitosis, collagen and TIMP-1 production. It can be safely used as a penetration enhancer for our formula to treat OSF.