Objective:To investigate the percutaneous penetration enhancement effect of essential oil from Zanthoxylum bungeanum Maxim.(Z.bungeanum oil)on active components in externally-applied traditional Chinese medicines.Meth...Objective:To investigate the percutaneous penetration enhancement effect of essential oil from Zanthoxylum bungeanum Maxim.(Z.bungeanum oil)on active components in externally-applied traditional Chinese medicines.Methods:Five model drugs,geniposide,puerarin,ferulic acid,tetramethylpyrazine,and osthole,were chosen based on their lipophilicity and tested using in vitro transdermal permeation studies consisting of Franz diffusion cells and full thickness rat abdominal skin.Scanning electron microscopy was employed to observe the morphological changes of rat skin tissue after treatment with Z.bungeanum oil.The molecular interactions between the oil and the polar head groups in stratum corneum(SC)lipids were monitored using molecular dynamic simulation,and the SC/vehicle partition coefficients and saturation solubilities of the selected model drugs treated with and without the oil were also determined to ascertain its mechanisms of action.Results:As oil concentration increased,the log ERflow trended toward a negative linear relationship with the lipophilicity of drugs.After treatment with Z.bungeanum oil,a mild lifting up and wrinkle on the SC surface were observed,and appeared to become more pronounced as oil concentration increased.There was no significant difference between the control and the Z.bungeanum oil at different concentrations in terms of saturation solubility of GP,while saturation solubilities of the 4 other drugs gradually increased as oil concentration increased.The oxygen-containing constituents in Z.bungeanum oil,such as terpinen-4-ol and 1,8-cineole,which accounted for 57.95%of total oil,could form stable hydrogen bonds with the polar head group of ceramide 3.Conclusion:Z.bungeanum oil facilitated transdermal permeation of drugs with different lipophilicity,including the extremely hydrophilic and lipophilic drugs,whereas it exhibited greater enhancement activity for strongly hydrophilic drugs.The mechanisms of transdermal permeation enhancement by the oil could be explained with SC/vehicle partition coefficient,saturation solubility,and the interactions with SC lipids.展开更多
The aim of this present study is to investigate the effect of Zanthoxylum bungeanum oil （essential oil from Z. bungeanum Maxim.） on cytotoxicity and the transdermal permeation of 5-fluorouracil and indomethacin. The...The aim of this present study is to investigate the effect of Zanthoxylum bungeanum oil （essential oil from Z. bungeanum Maxim.） on cytotoxicity and the transdermal permeation of 5-fluorouracil and indomethacin. The cy- totoxicity of Z. bungeanum oil on dermal fibroblasts and epidermal keratinocytes was studied using an MTT （3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide） assay. The rat skin was employed to determine the percutaneous penetration enhancement effect of Z. bungeanum oil on hydrophilic and lipophilic model drugs, i.e., 5-fluorouracil and indomethacin. The secondary structure changes of the rat stratum comeum （SC） were determined using attenuated total reflectance-Fourier transform infrared spectroscopy （ATR-FTIR）, and saturated solubilities and SC/vehicle partition coefficients of two model drugs with and without Z. bungeanum oil were also measured to un- derstand its related mechanisms of action. It was found that the half maximal inhibitory concentration （ICs0） values of Z. bungeanum oil were significantly lower in HaCaT and CCC-ESF-1 cell lines compared to the well-established and standard penetration enhancer Azone. The Z. bungeanum oil at various concentrations effectively facilitated the percutaneous penetration of two model drugs across the rat skin. In addition, the mechanisms of permeation en- hancement by Z. bungeanum oil could be explained with saturated solubility, SC/vehicle partition coefficient, and secondary structure changes of SC.展开更多
Our previous studies had confirmed that the essential oil from Zanthoxylum bungeanum Maxim. （Z. bungeanum oil） could effectively enhance the percutaneous permeation of drug molecules as a natural transdermal penetra...Our previous studies had confirmed that the essential oil from Zanthoxylum bungeanum Maxim. （Z. bungeanum oil） could effectively enhance the percutaneous permeation of drug molecules as a natural transdermal penetration enhancer. The aim of the present study is to investigate and compare the skin penetration enhancement effect of Z. bungeanum oil and its main components on traditional Chinese medicine （TCM） active components. Toxicities of Z. bungeanum oil and three selected terpene compounds （terpinen-4-ol, 1,8-cineole, and limonene） in epidermal keratinocytes （HaCaT） and dermal flbroblast （CCC-ESF-1） cell lines were measured using an MTT （3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide） assay. Five model drugs in TCM external preparations, namely osthole （OT）, tetramethylpyrazine （TMP）, ferulic acid （FA）, puerarin （PR）, and geniposide （GP）, which were selected based on their lipophilicity denoted by IogKo^w, were tested using in vitro permeation studies in which vertical Franz diffusion ceils and rat abdominal skin were employed. The secondary structure changes of skin stratum corneum （SC） and drug thermodynamic activities were investigated to understand their mechanisms of action using Fourier transform infrared （FTIR） spectroscopy and saturation solubility studies, respectively. It was found that Z. bungeanum oil showed lower toxicities in both HaCaT cells and CCC-ESF-1 cells compared with three terpene compounds used alone. The enhancement permeation capacities by all tested agents were in the following increasing order： terpinen-4-ol=1,8-cineole〈limonene〈Z, bungeanum oil. The mechanisms of permeation enhancement suggested that these enhancers promoted the skin permeation of drugs mainly by affecting SC lipids. These results indicated that Z. bungeanum oil exhibited better performance in enhancing the skin permeation of active components in TCM preparations.展开更多
基金National Natural Science Foundation of China(No.81473365)Postgraduate Project of Beijing University of Chinese Medicine(No.2016-JYB-XS095)The authors also thank the Innovative Research Team of Beijing University of Chinese Medicine(No.2011-CXTD-13)for its financial support.
文摘Objective:To investigate the percutaneous penetration enhancement effect of essential oil from Zanthoxylum bungeanum Maxim.(Z.bungeanum oil)on active components in externally-applied traditional Chinese medicines.Methods:Five model drugs,geniposide,puerarin,ferulic acid,tetramethylpyrazine,and osthole,were chosen based on their lipophilicity and tested using in vitro transdermal permeation studies consisting of Franz diffusion cells and full thickness rat abdominal skin.Scanning electron microscopy was employed to observe the morphological changes of rat skin tissue after treatment with Z.bungeanum oil.The molecular interactions between the oil and the polar head groups in stratum corneum(SC)lipids were monitored using molecular dynamic simulation,and the SC/vehicle partition coefficients and saturation solubilities of the selected model drugs treated with and without the oil were also determined to ascertain its mechanisms of action.Results:As oil concentration increased,the log ERflow trended toward a negative linear relationship with the lipophilicity of drugs.After treatment with Z.bungeanum oil,a mild lifting up and wrinkle on the SC surface were observed,and appeared to become more pronounced as oil concentration increased.There was no significant difference between the control and the Z.bungeanum oil at different concentrations in terms of saturation solubility of GP,while saturation solubilities of the 4 other drugs gradually increased as oil concentration increased.The oxygen-containing constituents in Z.bungeanum oil,such as terpinen-4-ol and 1,8-cineole,which accounted for 57.95%of total oil,could form stable hydrogen bonds with the polar head group of ceramide 3.Conclusion:Z.bungeanum oil facilitated transdermal permeation of drugs with different lipophilicity,including the extremely hydrophilic and lipophilic drugs,whereas it exhibited greater enhancement activity for strongly hydrophilic drugs.The mechanisms of transdermal permeation enhancement by the oil could be explained with SC/vehicle partition coefficient,saturation solubility,and the interactions with SC lipids.
基金supported by the National Natural Science Foundation of China(No.81073059)the Beijing Natural Science Foundation(No.7132127)the Innovative Research Team in Beijing University of Chinese Medicine(No.2011-CXTD-13),China
文摘The aim of this present study is to investigate the effect of Zanthoxylum bungeanum oil （essential oil from Z. bungeanum Maxim.） on cytotoxicity and the transdermal permeation of 5-fluorouracil and indomethacin. The cy- totoxicity of Z. bungeanum oil on dermal fibroblasts and epidermal keratinocytes was studied using an MTT （3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide） assay. The rat skin was employed to determine the percutaneous penetration enhancement effect of Z. bungeanum oil on hydrophilic and lipophilic model drugs, i.e., 5-fluorouracil and indomethacin. The secondary structure changes of the rat stratum comeum （SC） were determined using attenuated total reflectance-Fourier transform infrared spectroscopy （ATR-FTIR）, and saturated solubilities and SC/vehicle partition coefficients of two model drugs with and without Z. bungeanum oil were also measured to un- derstand its related mechanisms of action. It was found that the half maximal inhibitory concentration （ICs0） values of Z. bungeanum oil were significantly lower in HaCaT and CCC-ESF-1 cell lines compared to the well-established and standard penetration enhancer Azone. The Z. bungeanum oil at various concentrations effectively facilitated the percutaneous penetration of two model drugs across the rat skin. In addition, the mechanisms of permeation en- hancement by Z. bungeanum oil could be explained with saturated solubility, SC/vehicle partition coefficient, and secondary structure changes of SC.
基金supported by the Beijing Natural Science Foundation(No.7132127)the Innovative Research Team in Beijing University of Chinese Medicine(No.2011-CXTD-13),China
文摘Our previous studies had confirmed that the essential oil from Zanthoxylum bungeanum Maxim. （Z. bungeanum oil） could effectively enhance the percutaneous permeation of drug molecules as a natural transdermal penetration enhancer. The aim of the present study is to investigate and compare the skin penetration enhancement effect of Z. bungeanum oil and its main components on traditional Chinese medicine （TCM） active components. Toxicities of Z. bungeanum oil and three selected terpene compounds （terpinen-4-ol, 1,8-cineole, and limonene） in epidermal keratinocytes （HaCaT） and dermal flbroblast （CCC-ESF-1） cell lines were measured using an MTT （3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide） assay. Five model drugs in TCM external preparations, namely osthole （OT）, tetramethylpyrazine （TMP）, ferulic acid （FA）, puerarin （PR）, and geniposide （GP）, which were selected based on their lipophilicity denoted by IogKo^w, were tested using in vitro permeation studies in which vertical Franz diffusion ceils and rat abdominal skin were employed. The secondary structure changes of skin stratum corneum （SC） and drug thermodynamic activities were investigated to understand their mechanisms of action using Fourier transform infrared （FTIR） spectroscopy and saturation solubility studies, respectively. It was found that Z. bungeanum oil showed lower toxicities in both HaCaT cells and CCC-ESF-1 cells compared with three terpene compounds used alone. The enhancement permeation capacities by all tested agents were in the following increasing order： terpinen-4-ol=1,8-cineole〈limonene〈Z, bungeanum oil. The mechanisms of permeation enhancement suggested that these enhancers promoted the skin permeation of drugs mainly by affecting SC lipids. These results indicated that Z. bungeanum oil exhibited better performance in enhancing the skin permeation of active components in TCM preparations.
