Efficacy of borneol-gypsum in skin regeneration and pain control in toxic epidermal necrolysis:A case report

BACKGROUND Toxic epidermal necrolysis(TEN)is a life-threatening dermatological emergency mainly induced by drug hypersensitivity reactions.Standard management includes discontinuation of culprit drug and application of immunomodulatory therapy.However,mortality remains high due to complications like septic shock and multiorgan failures.Innovative approaches for skin care are crucial.This report introduces borneol-gypsum,a traditional Chinese drug but a novel dressing serving as an adjuvant of TEN therapy,might significantly improve skin conditions and patient outcomes in TEN.CASE SUMMARY A 38-year-old woman diagnosed with eosinophilic granulomatosis with polyangiitis experienced gangrenous complications and motor nerve involvement.After initial treatment of high-dose corticosteroids and cyclophosphamide,symptom of foot drop improved,absolute eosinophil counts decreased,while limb pain sustained.Duloxetine was added to alleviate her symptom.Subsequently,TEN developed.Additional topical application of borneol-gypsum dressing not only protected the skin lesions from infection but also significantly eased localized pain.This approach demonstrated its merit in TEN management by promoting skin healing and potentially reducing infection risks.CONCLUSION Borneol-gypsum dressing is a promising adjuvant that could significantly improve TEN management,skin regeneration,and patient comfort.

Research Progress on Application of Borneol As Permeation Enhancer in Functional Cosmetics

Borneol, as a traditional natural permeation enhancer, has been widely used to promote the transdermal absorption of active ingredients. In this review, the mechanism of borneol in promoting permeation by destroying the highly ordered lipid structure of the lipid layer and by destroying the hydrogen-bond network was described. The application of borneol in promoting the transdermal absorption of the active ingredients of traditional Chinese medicine and chemical drugs was introduced. The application of borneol as a natural ingredient added to functional cosmetics was summarized, and its effects on skin-spot treatment, acne skin care, eczema skin care, skin repair and anti-oxidation were introduced. Finally, the possible problems in the application of borneol in cosmetics were put forward, and the application prospect of borneol in the development of cosmetics was given.

Influence of puerarin,paeoniflorin,and menthol on structure and barrier function of tight junctions in MDCK and MDCK-MDR1 Cells

Objective:In this study,the influence of puerarin,paeoniflorin,and menthol on the structure and barrier function of tight junctions(TJs)in MadineDarby canine kidney epithelial(MDCK)and MDCK-multi-drug resistance 1(MDR1)cells was evaluated to determine the mechanisms by which the drugs cross the bloodebrain barrier(BBB).Method:Cells were treated with puerarin,paeoniflorin,and menthol followed by immunohistochemical staining with occludin,claudin-1,and F-actin.The cells were then observed using laser-scanning confocal microscopy.Average optical density(AOD)of the immunofluorescence images of the proteins were analyzed using ImageJ software while Transepithelial electrical resistance(TEER)was measured using an epithelial voltohmmeter.Results:Confocal microscopy revealed that puerarin-and paeoniflorin-treated tight junction proteins were conspicuous while menthol suppressed their expression.Correspondingly,AOD values of cells treated with puerarin or paeoniflorin,or both showed no difference compared to the control group(P>.05)while the menthol group value was downregulated.In 3 h,TEER of cells not treated with menthol were similar to the control group,while treatment with menthol significantly decreased TEER value(P<.05).In addition,application of menthol decreased TEER in MDCK cells earlier than in MDCK-MDR1 cells.Conclusion:Menthol but not puerarin and paeoniflorin may enhance paracellular transport and improve drug penetration of the BBB by disrupting the structure and,thereby,weakening the barrier function of TJs.

Research of Supercritical CO2 Fluid Refined Natural Borneol

In this study, with borneol fragments in the crystallized mother liquor of natural borneol used as the raw materials, supercritical carbon dioxide method is adopted for refining to get high purity borneol. The result of the experiment shows that the yield and purity are excellent with an extraction pressure of 11 MPa, an extracting temperature of 40°C, a carbon dioxide flow rate of 25 L·h-1 and an extraction time of 20 minutes. After detected by gas chromatography, the purity of the crystallization products could reach 96%.

A multiscale study of the penetrationenhancing mechanism of menthol

Objective:Transdermal drug delivery systems represent a critical focus in the pharmaceutics field;however,their use is limited by the fact that many drugs usually pass through the skin with low permeability.Menthol is a common penetration enhancer because of its high penetration-enhancing efficiency and safety.Our research aimed to reveal the penetrationenhancing mechanisms of menthol via a multiscale study.Methods:First,the interaction of menthol with the stratum corneum was studied using vertical Franz diffusion cells obtained from the abdominal skin of rats as a model.Then,the skin samples were observed via transmission electron microscopy.Finally,the interaction of different concentrations of menthol with a mixed lipid model of the stratum corneum was investigated via molecular dynamics simulation using the GROMOS 54A7 force field on a microcosmic level.Results:At concentrations of 3.5%or lower,menthol changed the original structure of the stratum corneum to varying degrees,which increased its fluidity and facilitated the permeation and storage of menthol.Menthol increased the fluidity of the stratum corneum mainly via two mechanisms.First,menthol had strong hydrogen-bonding capability,and it could compete for the lipidelipid hydrogen bonding sites,thereby weakening the stability of the hydrogenbonding network connecting the skin lipids.In addition,menthol had strong affinity for cholesterol,probably due to their similar molecular structures,suggesting that the incorporation of menthol would increase the fluidity of the lipid membrane similarly to cholesterol.Conclusion:The penetration-enhancing mechanism of menthol was explained using in vitro and molecular dynamics simulation methods.These findings may advance the basic research of transdermal drug delivery systems and facilitate the discoveries of novel penetration enhancers.

Chemical Composition of the Essential Oil and Nitrogen Metabolism of Menthol Mint under Different Phosphorus Levels

The purpose of this work was to evaluate the effects of different phosphorus levels (0.05, 0.5, 1 and 2 mM) under nitrogen metabolism and the essential oil profile of menthol mint (Mentha arvensis L.). The relationship between the leaf maturity and the essential oil profile was also explored. The experiment was conducted in a hydroponic system located in a grow chamber during 41 days and after the harvest, nitrate reductase activity, and the -N, amino-N, and soluble sugars levels of each plant part were evaluated. Also the essential oil from young leaves (6th to 8th node) and adult leaves (3rd to the 5th node) was analyzed. An uptake mechanism related to the increase in fresh weight of the roots was promoted with the use of low P levels (0.05 and 0.50 mmol&middotL-1). With 1 mmol&middotL-1 P plants showed in all parts an increased nitrate reductase activity and high levels of nitrate and amino-N in leaves. Plants submitted to the lowest P level (0.05 mmol&middotL-1) presented high levels of menthol. In leaves from 6th to 8th node (mature leaves) menthol level was approximately 87% of the essential oil however leaves from the 3rd to the 5th node (young leaves) showed high levels of pulegone, that can be toxic for humans. The results indicate that the essential oil quality in menthol mint is influenced by the leaf maturity and the P levels. Also it was showed that the oil extracted from mature leaves of plants under low P levels has the best commercial profile.

Analysis of pathomechanisms involved in side effects of menthol treatment in respiratory diseases

Menthol is frequently used in over the counter medications for common colds and coughs. It was formerly considered to be under the class of herbal medicine, but identification of menthol receptor (TRPM8) moved it from the class of herbal medicine to the molecular pharmacology. It has been documented that menthol reduces dyspnoea and nasal obstruction via stimulation of nasal cold or flow receptors. It has also antitussive and antiirritative effect. Menthol can also induce adverse reactions such as airway irritation, dyspnoea, chest tightness and potentially respiratory failure, mainly in children. The mechanisms responsible for adverse reactions of menthol are not known completely. The adverse reactions of menthol could be due to its effects on TRPA1 channel, relevant to airway irritation. Higher concentrations of menthol stimulate TRPA1 channel causing airway irritation. It also increases mucus production and at the same time reduces cilliary activity leading to mucus stagnation. As the adverse effects were reported mainly at the night it is supposed that suppressed cough reflex during sleep potentiated by menthol induced cough suppression might be responsible for lack of airway mucus clearing and obliteration of small airways. Adverse effects could also be due to consequences of reflexes induced by the menthol action on trigeminal afferents, like apnoea or bronchoconstriction. Menthol is effective in relieving respiratory symptoms, but cough and cold medications should be used with caution. Recommendations are low concentrations of menthol used locally (intranasal) and not combined with camphor or cineole, as they may have additive effects and should be avoided in children under 2 years. Further data are necessary to completely elucidate potential risks of over the counter menthol medication in children but based on the meta analysis of documented case reports, menthol can be used safely if its contraindications for use are followed as with any other over the counter medications.

Nicotine and menthol independently exert neuroprotective effects against cisplatin-or amyloid-toxicity by upregulating Bcl-xl via JNK activation in SH-SY5Y cells

Nicotine and menthol,agonists of nicotinic acetylcholine receptor(nAChR)and transient receptor potential melastatin type 8(TRPM8),serve important roles in the prevention of cell death-involved neurodegenerative diseases.However,the potential synergistic effects of nicotine and menthol on anti-apoptotic ability are still uncertain.In the present study,the potential synergistic effects of nicotine and menthol on cisplatin or amyloidβ1-42 induced cell model of the neurodegenerative diseases were explored by assessing cell viability,TNF-αexpression,caspase-3 activation,and the collapse of mitochondrial membrane potential in human SH-SY5Y neuroblastoma cells.Statistical significance was tested using Student’s t-test or one-way ANOVA with post hoc Newman-Keuls test.The results showed that:Firstly,SH-SY5Y cell viability was obviously increased by the treatments with nicotine and menthol.Secondly,nicotine and menthol independently alleviated cisplatin or amyloidβ1-42 induced TNF-αup-regulation.Thirdly,nicotine and menthol abrogated the effect of cisplatin and amyloidβ25-35 on caspase-3 activation.Interestingly,the effect of cisplatin and amyloidβ1-42 on the collapse of mitochondrial membrane potential was efficiently attenuated by nicotine and menthol treatments.Most importantly,the inhibition of c-jun kinase(JNK)activation abolished the effect of cisplatin,and amyloidβ1-42 stimulated Bcl-xl expression.All these findings indicate that nicotine and menthol independently exert neuroprotective effects by upregulating Bcl-xl via JNK activation.Nicotine and menthol augmented Bcl-xl expression and JNK phosphorylation,and thus they are potential therapeutic targets for altering the progress of neurodegenerative diseases.

A New Convenient Method for the Resolution of 1, 1'-Binaphthalene-2, 2'-diol Via a Phosphite Using (-)-Menthol as Resolving Agent

Menthol reacts with phosphorus trichloride to afford menthyl phosphorodichloridite 2, which further reacts with racemic 1, 1-binaphthalene-2, 2-diol to give phosphite (+)-3 in the presence of triethylamine. (+)-3 can be easily separated by fractional crystallization to form the crystal (+)-(S)-3 and the mother liquor (-)-(R)-3. Then both the crystal and the mother liquor are treated with AcOH-H2O to obtain enantiomeric pure (-)-(S)-1 and (+)-(R)-1 respectively, with enantiomeric excess up to 99.7%.

Effect of borneol and electroacupuncture on the distribution of hyperforin in the rat brain

Hyperforin is an antidepressant drug that has unstable therapeutic effects, due to its poor ability to cross the blood-brain barrier. Borneol and electroacupuncture have both been found to increase the permeability of the blood-brain barrier. As such, the current study examined the distribution of hyperforin in the rat brain, and the effects on the brain distribution of hyperforin of borneol alone （orally administered）, and borneol combined with electroacupuncture treatment. High-performance liquid chromatography technology and pharmacokinetic analysis revealed that treatment with borneol alone （300, 600 mg/kg） increased peak concentration and the area under the curve for hyperforin in the brain. In addition, the bioavailability of hyperforin in rat brain increased by 42.7%. However, increasing the dose of borneol dose did not appear to increase the distribution of hyperforin in the brain. Importantly, applying electroacupuncture at Baihui （GV 20） or Yamen （GV 15） appeared to enhance the brain-delivery effects of borneol, although this effect was weak. Overall, our results indicated that borneol alone or combined with electroacupuncture can provide promising strategies for brain-targeted delivery in central nervous system therapy.

Effect of borneol, moschus, storax, and acorus tatarinowii on expression levels of four amino acid neurotransmitters in the rat corpus striatum

The present study collected cerebrospinal fluid samples from the corpus striatum in rats treated with borneol, moschus, storax, and acorus tatarinowii using brain microdialysis technology. Levels of excitatory neurotransmitters aspartic acid and glutamate, as well as inhibitory neurotransmitters glycine and ^-aminobutyric acid, were measured in samples using reversed-phase high-performance liquid chromatography, phosphate gradient elution, and fluorescence detection. Results showed that concentrations of all four amino acid neurotransmitters significantly increased in the corpus striatum following treatment with borneol or moschus, but effects due to borneol were more significant than moschus. Acorus tatarinowii treatment increased ^-aminobutyric acid expression, but decreased glutamate concentrations. Storax increased aspartic acid concentrations and decreased glycine expression. Results demonstrated that borneol and moschus exhibited significant effects on con amino acid neurotransmitter expression; storax exhibited excitatory effects and acorus tatarinowii resulted in inhibitory effects.

Percutaneous absorption and brain distribution facilitation of borneol on tetramethylpyrazine in a microemulsion-based transdermal therapeutic system

In this study, we show that the percutaneous absorption and brain distribution of tetramethylpyrazine(TMP) is enhanced when combined with borneol(BN) in a microemulsionbased transdermal therapeutic system(ME-TTS). The formulation of the TMP and BN microemulsion(TEM-BN-ME) was optimized in skin permeation studies in vitro following a uniform experimental design. Male Sprague-Dawley rats were used for the in vivo pharmacokinetic and tissue distribution studies of TMP-BN-ME-TTS. In the pharmacokinetic study, the TMP-BN-ME-TTS treated rats had significantly higher( P < 0.05) C max and AUC of TMP than the TMP-ME-TTS treated rats, indicating that BN improves the rate and extent of TMP percutaneous absorption. In the tissue distribution study, the AUC of TMP in brain was significantly higher in the TMP-BN-ME-TTS group( P < 0.05), indicating that BN facilitates the distribution of TMP in brain. In summary, BN enhanced the percutaneous absorption and brain distribution of TMP in a microemulsion-based transdermal therapeutic system.

Lipid-albumin nanoassemblies co-loaded with borneol and paclitaxel for intracellular drug delivery to C6 glioma cells with P-gp inhibition and its tumor targeting

Successful chemotherapy with paclitaxel(PTX)is impeded by multidrug resistance(MDR)in tumor cells.In this study,lipid-albumin nanoassemblies co-loaded with borneol and paclitaxel(BOR/PTX LANs)were prepared to circumvent MDR in C6 glioma cells.The physiochemical properties including particle size,encapsulation efficiency and morphology were evaluated in vitro.Quantitative and qualitative investigations of cellular uptake were carried out in C6 glioma cells.The cytotoxicity of the BOR/PTX LANs was determined by MTT assay.After that,the tumor targeting was also evaluated in C6 glioma bearing mice by in vivo imaging analysis.BOR/PTX LANs have a higher entrapment efficiency(90.4±1.2%),small particle size(107.5±3.2 nm),narrow distribution(P.I.=0.171±0.02).The cellular uptake of PTX was significantly increased by BOR/PTX LANs compared with paclitaxel loaded lipidalbumin nanoassemblies(PTX LANs)in quantitative research.The result was further confirmed by confocal laser scanning microscopy qualitatively.The cellular uptake was energy-,timeand concentration-dependent,and clathrin-and endosome/lysosome-associated pathways were involved.The BOR/PTX LANs displayed a higher cytotoxicity agaist C6 glioma cells in comparion with PTX LANs and Taxol.Moreover,the encapsulation of BOR in LANs obviously increased the accumulation of the drug in tumor tissues,demonstrating the tumor targeted ability of BOR/PTX LANs.These results indicated that BOR/PTX LANs could overcome MDR by combination of drug delivery systems and P-gp inhibition,and shown the potential for treatment of gliomas.

Exploring the potential to enhance drug distribution in the brain subregion via intranasal delivery of nanoemulsion in combination with borneol as a guider

The number of people with Alzheimer’s disease(AD)is increasing annually,with the nidus mainly concentrated in the cortex and hippocampus.Despite of numerous efforts,effective treatment of AD is still facing great challenges due to the blood brain barrier(BBB)and limited drug distribution in the AD nidus sites.Thus,in this study,using vinpocetine(VIN)as a model drug,the objective is to explore the feasibility of tackling the above bottleneck via intranasal drug delivery in combination with a brain guider,borneol(BOR),using nanoemulsion(NE)as the carrier.First of all,the NE were prepared and characterized.In vivo behavior of the NE after intranasal administration was investigated.Influence of BOR dose,BOR administration route on drug brain targeting behavior was evaluated,and the influence of BOR addition on drug brain subregion distribution was probed.It was demonstrated that all the NE had comparable size and similar retention behavior after intranasal delivery.Compared to intravenous injection,improved brain targeting effect was observed by intranasal route,and drug targeting index(DTI)of the VIN–NE group was 154.1%,with the nose-to-brain direct transport percentage(DTP)35.1%.Especially,remarkably enhanced brain distribution was achieved after BOR addition in the NE,with the extent depending on BOR dose.VIN brain concentration was the highest in the VIN-1-BOR-NE group at BOR dose of 1 mg/kg,with the DTI reaching 596.1%and the DTP increased to 83.1%.BOR could exert better nose to brain delivery when administrated together with the drug via intranasal route.Notably,BOR can remarkably enhance drug distribution in both hippocampus and cortex,the nidus areas of AD.In conclusion,in combination with intranasal delivery and the intrinsic brain guiding effect of BOR,drug distribution not only in the brain but also in the cortex and hippocampus can be enhanced significantly,providing the perquisite for improved therapeutic efficacy of AD.

Simultaneous determination of borneol and its metabolite in rat plasma by GC-MS and its application to pharmacokinetic study

A gas chromatography mass spectrometry （GC-MS） method has been developed and fully validated for the simultaneous determination of natural borneol （NB） and its metabolite, camphor, in rat plasma. Following a single liquid-liquid extraction, the analytes were separated using an HP-5MS capillary column （0.25 mm ？ 30 m ？ 0.25μm） and analyzed by MS in the selected ion monitoring mode. Selected ion monitor （m/z） of borneol, camphor and internal standard was 95, 95 and 128, respectively. Linearity, accuracy, precision and extraction recovery of the analytes were all satisfactory. The method was successfully applied to pharmacokinetic studies of NB after oral administration to Wistar rats.

Research Progress on Application of Borneol as Permeation Enhancer in Functional Cosmetics

Borneol,as a traditional natural permeation enhancer,has been widely used to promote the transdermal absorption of active ingredients.The mechanism of borneol in promoting permeation by destroying the highly ordered lipid structure of the lipid layer and by destroying the hydrogen-bond network was described.The application of borneol in promoting the transdermal absorption of the active ingredients of traditional Chinese medicine and chemical drugs was introduced.The application of borneol as a natural ingredient added to functional cosmetics was summarized,and its effects on skin-spot treatment,acne skin care,eczema skin care,skin repair and anti-oxidation were introduced.Finally,the possible problems in the application of borneol in cosmetics were put forward,and the application prospect of borneol in the development of cosmetics was given。

Protective effect of borneol combined with safflower on neurovascular unit in rats with ischemic stroke

Background:Compatibility is a characteristic of the clinical application of traditional Chinese medicine,often leading to enhanced therapeutic effects.In the treatment of cerebral ischemia,blood-activating and open orifices herbs are frequently used individually;however,their combination is not commonly practiced.This study aims to investigate the impact of combining safflower and borneol as examples of open orifices herbs and blood-activating herbs on the neurovascular unit in rats with ischemic stroke.The objective is to determine whether this combination exhibits superior therapeutic efficacy compared to using borneol or safflower alone while exploring its underlying mechanism.These findings may provide novel insights for clinical treatments.Methods:SD male rats were randomly divided into 6 groups:sham operation group,model group,borneol group(0.1 g/kg),safflower group(5 g/kg),borneol combined with safflower group(0.1 g/kg+5 g/kg)and nimodipine group(0.01 g/kg).The middle cerebral artery cerebral ischemia(MCAO)model were prepared after continuous intragastric administration for 7 days in each group,the neurological function of each group were scored 24h after operation,and water content in brain tissue were measured by weighing method.The activity of superoxide dismutase(SOD)and the contents of nitric oxide(NO)and malondialdehyde(MDA)in brain tissue and serum were determined by spectrophotometry,and the mRNA expressions of matrix metalloproteinase 2(MMP-2),tight junction protein 1(ZO-1),vascular endothelial growth factor(VEGF)and brain-derived neurotrophic factor(BDNF)were detected by Real time PCR.Result:Compared with the model group,the group treated with borneol combined with safflower exhibited a significant decrease in the neural function score of MCAO rats(P<0.01).Additionally,it led to a reduction in brain tissue water content(P<0.01),elevated SOD activity,and reduced levels of NO and MDA in both serum and brain tissue(P<0.01 or P<0.05).Moreover,this treatment resulted in a decrease in the mRNA expression of MMP-2 and an increase in ZO-1 in brain tissue,along with an increase in the mRNA expression of VEGF and BDNF(P<0.01).Conclusion:Borneol combined with safflower demonstrates a protective effect on the neurovascular unit in rats with ischemic stroke.This effect is likely associated with increased SOD activity,reduced MDA and NO content in both serum and brain tissue of MCAO rats,and a decrease in MMP-2 mRNA expression in brain tissue,coupled with an increase in ZO-1,VEGF,and BDNF mRNA expression.These effects were superior to those observed with borneol or safflower administered alone.

Topical treatment of tyrosine kinase 2 inhibitor through borneol-embedded hydrogel:Evaluation for preventive,therapeutic,and Recurrent management of psoriasis

Psoriasis,an immune-mediated inflammatory skin disorder characterized by a chronically relapsing-remitting course,continues to be primarily managed through topical therapy.While oral administration of tyrosine kinase 2 inhibitors(TYK2i)stands as an effective approach for psoriasis treatment,the potential efficacy of topical application of TYK2i remains unexplored.Herein,the carbomer/alginic acid hydrogel is embedded with borneol(BO)as a new topical carrier of TYK2i for achieving enhanced transdermal permeation and anti-psoriasis efficacy.The hydrogel system,i.e.,TYK2i-BO-gel,exhibits significantly improved preventative and therapeutic effects in mice models of psoriasiform dermatitis,as evidenced by phenotypical images,psoriasis severity score index(PSI),histology,immunohistochemical staining,and PCR analysis.Remarkably,TYK2i-BO-gel outperforms conventional topical corticosteroid therapy by significantly preventing psoriatic lesion recurrence as measured by a nearly 50%reduction in ear thickness changes(p<0.0001),PSI(p<0.0001)and epidermal thickness(p<0.05).Moreover,a strengthened anti-inflammatory effect caused by TYK2i-BO-gel is seen in a human skin explant model,implying its potential application for human patients.With the addition of BO,the TYK2i-BO-gel not only increases skin permeability but also inhibits the expression of antimicrobial peptides in keratinocytes and facilitates the anti-Th17 response of TYK2i with suppressed activation of STAT3.Therefore,this work represents the accessibility and effectiveness of TYK2i-BO-hydrogel as a new topical formulation for anti-psoriasis management and shows great potential for clinical application.

Menthol-modified casein nanoparticles loading 10-hydroxycamptothecin for glioma targeting therapy

Chemotherapy outcomes for the treatment of glioma remains unsatisfactory due to the inefficient drug transport across the blood–brain barrier(BBB) and insufficient drug accumulation in the tumor region. Although many approaches, including various nanosystems, have been developed to promote the distribution of chemotherapeutics in the brain tumor, the delivery efficiency and the possible damage to the normal brain function still greatly restrict the clinical application of the nanocarriers.Therefore, it is urgent and necessary to discover more safe and effective BBB penetration and gliomatargeting strategies. In the present study, menthol, one of the strongest BBB penetration enhancers screened from traditional Chinese medicine, was conjugated to casein, a natural food protein with brain targeting capability. Then the conjugate self-assembled into the nanoparticles to load anti-cancer drugs.The nanoparticles were characterized to have appropriate size, spheroid shape and high loading drug capacity. Tumor spheroid penetration experiments demonstrated that penetration ability of mentholmodified casein nanoparticles(M-CA-NP) into the tumor were much deeper than that of unmodified nanoparticles. In vivo imaging further verified that M-CA-NPs exhibited higher brain tumor distribution than unmodified nanoparticles. The median survival time of glioma-bearing mice treated with HCPT-MCA-NPs was significantly prolonged than those treated with free HCPT or HCPT-CA-NPs. HE staining ofthe organs indicated the safety of the nanoparticles. Therefore, the study combined the advantages of traditional Chinese medicine strategy with modern delivery technology for brain targeting, and provide a safe and effective approach for glioma therapy.

Enhancing effect of natural borneol on the absorption of geniposide in rat via intranasal administration

Both geniposide （Ge） and natural borneol （NB） are bioactive substances derived from traditional Chinese herbs. The effect of NB on the pharmacokinetics of Ge in rat via intranasal administration was investigated. The concentrations of Ge in plasma were determined by reversed-phase high-performance liquid chromatography （HPLC） after intranasal administration of Ge （4 mg/kg） alone and combined with different doses （0.08, 0.8, and 8 mg/kg） of NB. The intravenous administration was given as a reference （4 mg/kg of Ge and 8 mg/kg of NB）. Compared with the intravenous administration, the absolute bioavailability of Ge was 76.14% through intranasal administration combined with NB. Compared with the intranasal administration of Ge alone, Ge could be absorbed rapidly in the nasal cavity combined with NB; the peak time of Ge in the plasma became shorter （3-5 min vs. 40 min）; the peak concentration became higher （1.32-4.25 IJg/ml vs. 0.67 ug/ml）; and, the relative bioavailability of Ge combined with NB was 90.3%-237.8%. The enhancing effect was attenuated as the dose of NB decreased. The results indicated that NB can accelerate the absorption of Ge dose-dependently in the nasal cavity.