目的 基于网络药理学分析辛热中药挥发油外用的药效物质基础及潜在分子机制。方法 采用气相色谱-质谱联用技术分析高良姜Alpiniae Officinarum Rhizoma、干姜Zingiberis Rhizoma、肉桂Cinnamomi Cortex、吴茱萸Euodiae Fructus、胡椒Piperis Fructus 5种辛热中药挥发油的质量分数，并与防风Saposhnikoviae Radix等10味辛温中药挥发油进行比较，得到差异倍半萜类化合物；采用中药系统药理学数据库与分析平台（TCMSP）和Swiss Target Prediction数据库对差异倍半萜类化合物进行靶点预测，采用TIGER数据库筛选在皮肤中表达的蛋白，用Cytoscape 3.7.0软件建立“药材-成分-靶点”网络，并用STRING数据库建立潜在关键靶点的蛋白质-蛋白质互作（protein-protein interaction，PPI）网络。结果 辛热中药挥发油中倍半萜类成分质量分数高于辛温中药挥发油，倍半萜类成分在辛热中药挥发油外用给药时更倾向于滞留在皮内，是决定透皮促渗能力的关键成分，可能为辛热中药挥发油的关键物质基础。“药材-成分-靶点”网络及PPI结果表明辛热中药挥发油外用主要涉及产热相关的核受体共激活蛋白2（nuclear receptor coactivator 2，NCOA2）靶点及脂代谢相关的过氧化物酶体增殖剂激活受体α（peroxisome proliferator-activated receptor α，PPARA）、类视黄酸X受体α（retinoic acid X receptor α，RXRA）、NCOA2靶点及抗炎相关的前列腺素内过氧化物合酶1（prostaglandin G/H synthase 1，PTGS1）、PTGS2、白细胞介素-6（interleukin-6，IL-6）靶点，提示产热、减脂、抗炎为辛热中药挥发油倍半萜类成分的主要药理作用。结论 β-石竹烯、α-muurolene、吉马烯、β-榄香烯、δ-榄香烯、β-芹子烯、α-胡椒烯等倍半萜类成分为辛热中药挥发油的特征组分，可能通过作用于PPARA-RXRA-NCOA2信号轴及PTGS2、PTGS1、IL-6等炎性因子，从而产生产热、减脂、抗炎等作用。

Objective To explore the pharmacodynamic material basis and potential molecular mechanism for external use of essential oils extracted from "hot" pungent Chinese materia medica (CMM) based on network pharmacology. Methods The mass fraction of oil components from five kinds of pungent and "hot" Chinese medicines of Gaoliangjiang (Alpiniae Officinarum Rhizoma), Ganjiang (Zingiberis Rhizoma), Rougui (Cinnamomi Cortex), Wuzhuyu (Euodiae Fructus), and Hujiao (Piperis Fructus) were analyzed by GC-MS, the contents in "hot" pungent essential oils which were significantly different from that in pungent and warm CMM such as Fangfeng (Saposhnikoviae Radix) were obtained. TCMSP and Swiss Target Prediction database were used to predict the potential targets of sesquiterpenoids. TIGER database was applied to screen the proteins expressed in the skin, and Cytoscape 3.7.0 was utilized to complete the visualization of "medicinal materials- components-targets" network. PPI network of the potential key targets was established by STRING database. Results The contents of sesquiterpenoids in the essential oil extracted from "hot" pungent CMM were significantly higher than that in the essential oil extracted from pungent and warm CMM. The sesquiterpenoids from essential oil extracted from "hot" pungent CMM tended to stay in the skin when it was administered externally, and they were also the key components that determine the penetration enhancement ability into the skin, which were the key effective substances of the essential oils extracted from "hot" pungent CMM. The network of "medicinal materials-components-targets" and PPI network showed that the potential targets for external use of essential oils extracted from "hot" pungent CMM mainly focused on three functions, such as heat production including nuclear receptor coactivator 2 (NCOA2), lipid metabolism including peroxisome proliferator-activated receptor α (PPARA), retinoic acid X receptor α (RXRA), NCOA2, and anti-inflammation including prostaglandin G/H synthase 1 (PTGS1), PTGS2, interleukin-6 (IL-6), which indicated that thermogenesis, fat reduction, and anti-inflammation were the main pharmacological effects of sesquiterpenoids in the essential oils extracted from "hot" pungent CMM. Conclusion β-Caryophyllene, α-muurolene, germacrene, β-elemene, δ-elemene, β-selinene, α-copaene, and other sesquiterpenoids were the characteristic groups of essential oils of "hot" pungent CMM. The PPARA-RXRA-NCOA2 signal axis and inflammatory factors such as PTGS2, PTGS1, and IL-6 were the common targets for the essential oils extracted from "hot" pungent CMM, which resulted in biological effects such as thermogenesis, fat reduction, and anti-inflammation of essential oils.

R285.5

江苏省中药资源产业化过程协同创新中心重点项目（ZDXM-2020-25）