热性中药挥发油透皮促渗能力与倍半萜角质层贮库效应的相关性研究

Correlation between penetration enhancement ability and stratum corneum reservoir effect of sesquiterpenes of essential oils from traditional Chinese medicine with hot property

目的 研究热性中药挥发油影响皮肤屏障功能、发挥透皮促渗作用的主要机制。方法 采用水蒸气蒸馏法制备高良姜Alpiniae Officinarum Rhizoma、干姜Zingiberis Rhizoma、胡椒Piperis Fructus、肉桂Cinnamomi Cortex、吴茱萸Euodiae Fructus 5种热性中药挥发油,测定相对密度和折光率等理化参数,利用GC-MS分析挥发油的化学成分及经皮给药后倍半萜类成分在皮肤角质层内的驻留行为。以经皮水分流失值(transepidermal water loss,TEWL)评价挥发油对大鼠皮肤屏障功能的影响即透皮促渗能力,采用在体红斑分析考察挥发油的皮肤刺激性,通过相关性分析考察热性中药挥发油倍半萜角质层贮库效应与其对皮肤屏障功能影响之间的相关性。结果 5种热性中药挥发油均含有一定比例的倍半萜类成分,经皮给药后能够驻留于角质层中。经皮给药后挥发油能够显著提升大鼠皮肤TEWL,其排序为高良姜油>干姜油>胡椒油>肉桂油>吴茱萸油,红斑分析表明热性中药挥发油的皮肤刺激性均显著低于化学促渗剂氮酮,但不同挥发油之间没有显著性差异。相关性分析结果表明,倍半萜在角质层驻留能力与其降低皮肤屏障功能显著相关。结论 倍半萜角质层贮库效应是热性中药挥发油发挥透皮促渗作用的重要机制,为诠释经皮外用途径下“热者易效”规律提供了依据。

Objective To study the main mechanism underlying the effects of essential oils(EOs)from traditional Chinese medicine(TCM)with hot property on skin barrier function and penetration enhancement.Methods EOs from Gaoliangjiang(Alpiniae Officinarum Rhizoma,AOR),Ganjiang(Zingiberis Rhizoma,ZR),Hujiao(Piperis Fructus,PF),Rougui(Cinnamomi Cortex,CC)and Wuzhuyu(Euodiae Fructus,EF)with hot nature were prepared by steam distillation.Their relative density and refractive index values were determined,respectively.The chemical composition of EOs and their distribution in the stratum corneum(SC)after dermal administration were analyzed by GC-MS.The transepidermal water loss(TEWL)values were used to evaluate the effect of EOs on the skin barrier function of rats.In addition,the skin irritation potential of EOs was investigated by in vivo erythema analysis.The correlation between the SC reservoir effect of sesquiterpenes of EOs and their effect on skin barrier function was investigated by correlation analysis.Results The results showed that the EOs from TCM with hot property all contained sesquiterpenes,which could reside in the SC after dermal administration.Then the EOs could significantly reduce skin TEWL values,and the order was as follows:AOR oil>ZR oil>PF oil>CC oil>EF oil.Erythema index analysis showed that the skin irritation of EOs was significantly lower than that of azone,but there was little significant difference among these EOs.The results of correlation analysis showed that the presence of sesquiterpenes in the SC was significantly related to reduced skin barrier function following dermal administration of EOs from TCM with hot property.Conclusion The present study indicated that the sesquiterpene SC reservoir effect may be the main mechanism underlying the penetration enhancement effect of the EOs from TCM with hot property,which provides a basis for the interpretation of the law of“higher effect of hot property”via the dermal delivery system.