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(MDR...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.展开更多
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...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.展开更多
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 relationshi...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·L-1). With 1 mmol·L-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·L-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.展开更多
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 diseas...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.展开更多
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...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.展开更多
A novel analytical procedure for the determination of gold by electrothermal atomic absorption spectrometry combined with selective liquid-liquid extraction by natural deep eutectic solvents(NADESs)is presented.The ex...A novel analytical procedure for the determination of gold by electrothermal atomic absorption spectrometry combined with selective liquid-liquid extraction by natural deep eutectic solvents(NADESs)is presented.The extraction ability of the NADESs prepared using menthol,thymol and camphor toward gold in hydrochloric acid solutions was studied.The extraction efficiency was improved by optimizing the parameters including the composition of the NADES s,the volume ratio of organic and aqueous phases,kinetics,and acidity of the solution.Quantitative determination of gold was carried out by electrothermal atomic absorption spectrometry directly in the NADES s phase dissolved in isopropyl alcohol.The extraction recovery of gold from 1 mol/L HCl with the NADESs based on menthol and camphor mixed in a molar ratio 1:1 was 99.7%at an enrichment factor of 100.The limits of detection and quantification of the proposed procedure were 1μg/L and 3.3μg/L,respectively,with a relative standard deviation of less than 5%.The developed procedure was applied for determination of gold in the certified reference material of ore,environmental and waste waters.展开更多
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...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.展开更多
An improved solvent free microwave extraction, in which a kind of microwave absorption medium （carbonyl iron powder） was used, was applied to the extraction of essential oil from dried menthol mint and orange peel w...An improved solvent free microwave extraction, in which a kind of microwave absorption medium （carbonyl iron powder） was used, was applied to the extraction of essential oil from dried menthol mint and orange peel without addition of any solvent and pretreatment. It took much less time of extraction （30 min） than microwave-assisted hydrodistillation （90 min） and conventional hydrodistillation （180 min）. The kinds of chemical compositions in essential oil extracted by different methods were almost the same and such improved solvent free microwave extraction can be a feasible way in extraction of essential oil from dried plant materials.展开更多
文摘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.
基金This work was supported by the Municipal Natural Science Foundation of Beijing(7162122).
文摘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.
文摘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·L-1). With 1 mmol·L-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·L-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.
基金supported by the Young Elite Scientists Sponsorship Program of China Association for Science and Technology(No.2016QNRC001)the National Natural Science Foundation of China(Nos.81771669,81273203).
文摘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.
文摘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.
基金Financial Support by the National Natural Science Foundation of China (No.29872016) the Hong Kong Polytechnic University ASD Fund are gratefully acknowledged.
基金supported by the Ministry of Science and High Education of the Russian Federation[GEOKHI RAS]
文摘A novel analytical procedure for the determination of gold by electrothermal atomic absorption spectrometry combined with selective liquid-liquid extraction by natural deep eutectic solvents(NADESs)is presented.The extraction ability of the NADESs prepared using menthol,thymol and camphor toward gold in hydrochloric acid solutions was studied.The extraction efficiency was improved by optimizing the parameters including the composition of the NADES s,the volume ratio of organic and aqueous phases,kinetics,and acidity of the solution.Quantitative determination of gold was carried out by electrothermal atomic absorption spectrometry directly in the NADES s phase dissolved in isopropyl alcohol.The extraction recovery of gold from 1 mol/L HCl with the NADESs based on menthol and camphor mixed in a molar ratio 1:1 was 99.7%at an enrichment factor of 100.The limits of detection and quantification of the proposed procedure were 1μg/L and 3.3μg/L,respectively,with a relative standard deviation of less than 5%.The developed procedure was applied for determination of gold in the certified reference material of ore,environmental and waste waters.
基金financial support from the National Natural Science Foundation of China(No.81573616,81690263 and81773911,China)the Development Project of Shanghai Peak Disciplines-Integrated Medicine(No.20150407,China)
文摘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.
文摘An improved solvent free microwave extraction, in which a kind of microwave absorption medium （carbonyl iron powder） was used, was applied to the extraction of essential oil from dried menthol mint and orange peel without addition of any solvent and pretreatment. It took much less time of extraction （30 min） than microwave-assisted hydrodistillation （90 min） and conventional hydrodistillation （180 min）. The kinds of chemical compositions in essential oil extracted by different methods were almost the same and such improved solvent free microwave extraction can be a feasible way in extraction of essential oil from dried plant materials.
