Objective To analyze the interactions between different structural types of volatile oil compo-nents(VOCs)and skin lipid molecules;and investigate the mechanism of volatile oil in Chi-nese materia medica(VOCMM)as pene...Objective To analyze the interactions between different structural types of volatile oil compo-nents(VOCs)and skin lipid molecules;and investigate the mechanism of volatile oil in Chi-nese materia medica(VOCMM)as penetration enhancers.Methods In this study;210 different structural types of VOCs were selected from the VOCMM penetration enhancer database;and the molecular docking experiments were conducted with three main lipid molecules of skin:ceramide 2(CER2);cholesterol(CHL);and free fatty acid(FFA).Each VOC was docked individually with each lipid molecule.Cluster analysis was used to explore the relationship between the binding energy of VOCs and their molecular struc-tures.Nine specific pathogen-free(SPF)Sprague Dawley(SD)rats were randomly divided in-to Control;Nootkatone;and 3-Butylidenephthalide groups for in vitro percutaneous experi-ments;with three rats in each group.The donor pool solutions were 3%gastrodin;3%gas-trodin+3%nootkatone;and 3%gastrodin+3%3-butylidenephthalide;respectively.The pen-etration enhancing effects of VOCs with higher binding energy were evaluated by comparing the 12-hour cumulative percutaneous absorption of gastrodin(Q12;µg/cm²).Results(i)Most of the VOCs were non-hydrogen bonded to the hydrophobic parts of CHL and FFA;and hydrogen bonded to the head group of CER2.Among them;sesquiterpene ox-ides showed the most pronounced binding affinity to CER2.The VOCs with 2-4 rings(in-cluding carbon rings;benzene rings;and heterocycles)demonstrated stronger binding affini-ty for three skin lipid molecules compared with the VOCs without intramolecular rings(P<0.01).(ii)According to the cluster analysis;most of the VOCs that bond well to CER2 had 2-3 intramolecular rings.The non-oxygenated VOCs were bonded to CER2 in a hydrophobic manner.The oxygenated VOCs were mostly bonded to CER2 by hydrogen bonding.(iii)The results of Franz diffusion cell experiment showed that the Q12 of Control group was 260.60±25.09µg/cm2;and the transdermal absorption of gastrodin was significantly increased in Nootkatone group(Q12=5503.00±1080.00µg/cm²;P<0.01).The transdermal absorption of gastrodin was also increased in 3-Butylidenephthalide group(Q12=495.40±56.98µg/cm²;P>0.05).(iv)The type of oxygen-containing functional groups in VOCs was also an influencing factor of binding affinity to CER2.Conclusion The interactions between different types of VOCs with different structures in the VOCMM and three skin lipid molecules in the stratum corneum were investigated at the molecular level in this paper.This research provided theoretical guidance and data support for the screening of volatile oil-based penetration enhancers;and a simple and rapid method for studying the penetration-enhancing mechanism of volatile oils.展开更多
The present paper is in the same time an overview of the literature concerning the alterations of lipids in the stratum corneum(SC) of atopic dogs and a review of data based on our publications. Knowing the importance...The present paper is in the same time an overview of the literature concerning the alterations of lipids in the stratum corneum(SC) of atopic dogs and a review of data based on our publications. Knowing the importance of the SC barrier function for against pathogens in atopic dermatitis, we show for the first time a detailed biochemical analysis of lipids corresponding to the same amount of proteins in the successive layers of canine SC taken using tape stripping and their specificity as compared to humans. Also we show new results concerning the changes in the composition for proteinbound ceramides, and for the other lipids in involved and non-involved skin areas in atopic dogs. We show how a topical or oral treatment can restore the SC lipid composition and reconstruct the barrier integrity by upregulating the biosynthesis of protein-bound ceramides.展开更多
The mechanism of enhancers （methanol,chloroform,azone and thiozone） was studied in vitro in mouse stratum corneum （SC）.Attenuated total reflectance Fourier-transform infrared spectroscopy （ATR-FTIR） was applied ...The mechanism of enhancers （methanol,chloroform,azone and thiozone） was studied in vitro in mouse stratum corneum （SC）.Attenuated total reflectance Fourier-transform infrared spectroscopy （ATR-FTIR） was applied to monitor the wavenumber shifts of CH2 stretching absorbance as well as the lipid content in the SC,which were used as criteria to explain the effect of the enhancers on mouse SC.The FTIR spectra record that treatment with these four enhancers would result in significant shifts toward higher wavenumber at vasCH2 and vsCH2 and the integration areas of vasCH2 and vsCH2 decrease when treatment of methanol and choloroform.It is concluded that these four enhancers could increase the gauche conformational isomer content of lipid CH2,made the lipid in the SC a more fluid state,thus the resistance of drug transdermal delivery was reduced.展开更多
基金National Science Foundation of China(82174093)Fundamental Research Funds for the Central Universities(BUCM-2019-JYB-JS-016).
文摘Objective To analyze the interactions between different structural types of volatile oil compo-nents(VOCs)and skin lipid molecules;and investigate the mechanism of volatile oil in Chi-nese materia medica(VOCMM)as penetration enhancers.Methods In this study;210 different structural types of VOCs were selected from the VOCMM penetration enhancer database;and the molecular docking experiments were conducted with three main lipid molecules of skin:ceramide 2(CER2);cholesterol(CHL);and free fatty acid(FFA).Each VOC was docked individually with each lipid molecule.Cluster analysis was used to explore the relationship between the binding energy of VOCs and their molecular struc-tures.Nine specific pathogen-free(SPF)Sprague Dawley(SD)rats were randomly divided in-to Control;Nootkatone;and 3-Butylidenephthalide groups for in vitro percutaneous experi-ments;with three rats in each group.The donor pool solutions were 3%gastrodin;3%gas-trodin+3%nootkatone;and 3%gastrodin+3%3-butylidenephthalide;respectively.The pen-etration enhancing effects of VOCs with higher binding energy were evaluated by comparing the 12-hour cumulative percutaneous absorption of gastrodin(Q12;µg/cm²).Results(i)Most of the VOCs were non-hydrogen bonded to the hydrophobic parts of CHL and FFA;and hydrogen bonded to the head group of CER2.Among them;sesquiterpene ox-ides showed the most pronounced binding affinity to CER2.The VOCs with 2-4 rings(in-cluding carbon rings;benzene rings;and heterocycles)demonstrated stronger binding affini-ty for three skin lipid molecules compared with the VOCs without intramolecular rings(P<0.01).(ii)According to the cluster analysis;most of the VOCs that bond well to CER2 had 2-3 intramolecular rings.The non-oxygenated VOCs were bonded to CER2 in a hydrophobic manner.The oxygenated VOCs were mostly bonded to CER2 by hydrogen bonding.(iii)The results of Franz diffusion cell experiment showed that the Q12 of Control group was 260.60±25.09µg/cm2;and the transdermal absorption of gastrodin was significantly increased in Nootkatone group(Q12=5503.00±1080.00µg/cm²;P<0.01).The transdermal absorption of gastrodin was also increased in 3-Butylidenephthalide group(Q12=495.40±56.98µg/cm²;P>0.05).(iv)The type of oxygen-containing functional groups in VOCs was also an influencing factor of binding affinity to CER2.Conclusion The interactions between different types of VOCs with different structures in the VOCMM and three skin lipid molecules in the stratum corneum were investigated at the molecular level in this paper.This research provided theoretical guidance and data support for the screening of volatile oil-based penetration enhancers;and a simple and rapid method for studying the penetration-enhancing mechanism of volatile oils.
文摘The present paper is in the same time an overview of the literature concerning the alterations of lipids in the stratum corneum(SC) of atopic dogs and a review of data based on our publications. Knowing the importance of the SC barrier function for against pathogens in atopic dermatitis, we show for the first time a detailed biochemical analysis of lipids corresponding to the same amount of proteins in the successive layers of canine SC taken using tape stripping and their specificity as compared to humans. Also we show new results concerning the changes in the composition for proteinbound ceramides, and for the other lipids in involved and non-involved skin areas in atopic dogs. We show how a topical or oral treatment can restore the SC lipid composition and reconstruct the barrier integrity by upregulating the biosynthesis of protein-bound ceramides.
文摘The mechanism of enhancers （methanol,chloroform,azone and thiozone） was studied in vitro in mouse stratum corneum （SC）.Attenuated total reflectance Fourier-transform infrared spectroscopy （ATR-FTIR） was applied to monitor the wavenumber shifts of CH2 stretching absorbance as well as the lipid content in the SC,which were used as criteria to explain the effect of the enhancers on mouse SC.The FTIR spectra record that treatment with these four enhancers would result in significant shifts toward higher wavenumber at vasCH2 and vsCH2 and the integration areas of vasCH2 and vsCH2 decrease when treatment of methanol and choloroform.It is concluded that these four enhancers could increase the gauche conformational isomer content of lipid CH2,made the lipid in the SC a more fluid state,thus the resistance of drug transdermal delivery was reduced.
