Study on the interaction between volatile oil components and skin lipids based on molecular docking techniques  

基于分子对接技术的挥发油成分与皮肤脂质相互作用研究

在线阅读下载全文

作  者:REN Weishuo WULAN Tuya DAI Xingxing ZHANG Yingying JIA Mingyue FENG Minfang SHI Xinyuan 任伟硕;乌兰图雅;戴幸星;张莹莹;贾明月;冯敏芳;史新元(北京中医药大学中药学院,北京102488;北京市科学技术委员会中药生产过程控制与质量评价重点实验室,北京102488;北京中医药大学生命科学学院,北京100029)

机构地区:[1]School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China [2]Key Laboratory for Production Process Control and Quality Evaluation of Traditional Chinese Medicine,Beijing Municipal Science&Technology Commission,Beijing 102488,China [3]School of Life Sciences,Beijing University of Chinese Medicine,Beijing 100029,China

出  处:《Digital Chinese Medicine》2024年第2期148-159,共12页数字中医药(英文)

基  金:National Science Foundation of China(82174093);Fundamental Research Funds for the Central Universities(BUCM-2019-JYB-JS-016).

摘  要: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 N目的分析不同结构类型挥发油成分(VOCs)与皮肤脂质分子间的相互作用,探究中药挥发油(VOCMM)作为促透剂的作用机制。方法本研究从VOCMM促渗数据库中选取210种不同结构类型的VOCs,并与皮肤的三种主要脂质分子:神经酰胺(CER2)、胆固醇(CHL)和游离脂肪酸(FFA)进行分子对接实验。每种VOC分别与每种脂质分子进行独立对接。通过聚类分析探讨VOCs的结合能与其分子结构之间的关系。取9只无特定病原体(SPF)级SpragueDawley(SD)大鼠进行离体透皮实验,将其随机分为对照组、圆柚酮组和正丁烯基苯酞组,每组3只,供给池溶液分别为3%天麻素、3%天麻素+3%圆柚酮和3%天麻素+3%正丁烯基苯酞。通过比较天麻素12小时单位面积累积透过量(Q12,µg/cm2)来评价结合能较强的VOCs的促透效果。结果(1)大多数VOCs通过非氢键作用影响CHL和FFA的疏水部分,而通过氢键作用与CER2的头基相结合,尤其是倍半萜氧化物类成分的结合能力最突出。与结构中无环状结构的VOCs相比,结构中具有2-4环的VOCs与三种脂质分子的结合能力较强(P<0.01)。(2)聚类分析表明,与CER2结合较好的VOCs多具有2-3个环结构。不含氧原子的VOCs主要通过疏水作用与CER2结合,而含氧原子的VOCs则多通过氢键与之结合。(3)Franz扩散池实验结果表明,对照组的Q12为260.60±25.09µg/cm2,圆柚酮组显著提高了天麻素的透皮吸收(Q12=5503.00±1080.00µg/cm2,P<0.01),正丁烯基苯酞组也提高了天麻素的透皮吸收(Q12=495.40±56.98µg/cm2,P>0.05)。(4)VOCs中含氧基团种类也是影响其与CER2结合能力的重要因素之一。结论本文从分子层面探究了中药挥发油中各类不同结构VOCs与皮肤角质层三种脂质分子之间的相互作用,为挥发油类促透剂的筛选提供了理论指导及数据支持,也为挥发油促透机理的研究提供了一种简便、快速的方法。

关 键 词:Chinese materia medica Volatile oil Stratum corneum lipids Transdermal penetration-enhancing effects Molecular docking Ceramide 2(CER2) Penetration enhancers 

分 类 号:R285[医药卫生—中药学]

 

参考文献:

正在载入数据...

 

二级参考文献:

正在载入数据...

 

耦合文献:

正在载入数据...

 

引证文献:

正在载入数据...

 

二级引证文献:

正在载入数据...

 

同被引文献:

正在载入数据...

 

相关期刊文献:

正在载入数据...

相关的主题
相关的作者对象
相关的机构对象