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Abstract: 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 fibroblast (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 logK _o/w, were tested using in vitro permeation studies in which vertical Franz diffusion cells 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.

花椒挥发油与其主要成分经皮促透作用的比较研究

比较花椒挥发油与其主要成分作为经皮促透剂的皮肤细胞毒性，对系列不同油水分配系数药物促透作用特征及其作用机制。 选择系列不同油水分配系数中药活性成分简化并表征中药制剂中复杂有效成分，对比研究花椒挥发油与其主要成分的经皮促透作用特征差异。 利用表皮角质形成细胞（HaCaT）和真皮成纤维细胞（CCC-ESF-1）测定其皮肤细胞毒性，选择系列不同油水分配系数中药活性成分作为模型药物测定花椒挥发油与其主要成分的经皮促透作用特征差异，并在此基础上采用傅利叶变换红外光谱（FTIR）等研究其促透作用机制。 花椒挥发油相对于其单一组成成分具有更好的经皮促透效果。
花椒挥发油；柠檬烯；促透剂；表皮角质形成细胞（HaCaT）；傅利叶变换红外光谱（FTIR）

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