基于粘液质理论4种抗白癜风维吾尔族药材的网络药理学机制研究

The network pharmacological mechanisms of four anti-vitiligo Uyghur medicines based on Phlegmatic temperament theory

粘液质理论成功应用于白癜风临床治疗,遂通过4种代表性维吾尔族药材展开抗白癜风的网络药理学机制研究。收集抗白癜风维吾尔族药方及其化合物,通过admet SAR方法筛选活性化合物并使用b SDTNBI方法预测活性化合物的靶点。通过DAVID数据库分析靶点的生物学过程（BP）和分子功能（MF）。构建维吾尔族药材-活性化合物-靶点-生物学过程-体液网络模型（MCTBHI network）,分析关键药材、活性化合物、关键靶点及相关体液系统的网络拓扑学参数。建立C57BL/6小鼠体外促黑色素生成模型,验证所筛选活性化合物促黑色素生成的效果。在调节粘液质的7种维吾尔药方中,找到补骨脂、驱虫斑鸠菊、丁香和阿纳其根4种关键药材。共筛选出22个活性化合物,主要为香豆素类和黄酮类结构。预测出58个靶点,其MF与类固醇激素受体活性、血红素结合和酶结合密切相关。BP在维吾尔医体液环境中排在第一位的是血液,其次分别是淋巴液、脑脊液、消化液。靶点在组织器官mRNA表达丰度在皮肤与体液中的占优,以山柰素和异鼠李素为代表的黄酮类化合物对ESR1,PTGS2,PPARA,PPARG,PTGS1,CA2等靶点关联密切。最后验证山柰素和异鼠李素具有促进C57BL/6小鼠耳部外侧皮肤的黑色素生成。该文解析了抗白癜风维吾尔族药材的潜在网络药理学机制,为理解粘液质的科学内涵提供了相关线索。

To explore the network pharmacological mechanisms of four anti-vitiligo Uyghur medicines based on the Phlegmatic temperament theory. First,The anti-vitiligo Uyghur medicine formulas based on Phlegmatic temperament theory were collected. The pharmacokinetic characteristic of main compounds in four anti-vitiligo Uyghur medicines were obtained by using admet SAR. The targets of active compounds were predicted via b SDTNBI（ balanced substructure-drug-target network-based inference model） method. Then,biological process（ BP） and molecular function（ MF） enrichment analysis of targets were analysed via DAVID database. Constructing anti-vitiligo Uyghur medicine formula-Uyghur medicines network model（ FMI network） and Uyghur medicines-active compounds-targetsBP-Hilit network model（ MCTBHI network）,we utilized closeness centrality to analyse key Uyghur medicines,active compounds,key targets as well as Hilit. Finally,the in vitro melanin production model of C57 BL/6 mice was used to verify the ability of the active compounds to improve melanogenesis. The results showed that Psoralea corylifolia,Vernonia anthelmintica,Syzygium aromaticum and Anacyclus pyrethrum were the key Uyghur medicines in the FMI network. There were 22 active compounds with a relatively higher bioavailability interacted with 58 therapeutic targets. These active compounds were mainly composed of coumarins and flavonoids. In the MCTBHI network,the MF of 58 therapeutic targets was related to steroid hormone receptor activity,heme binding and enzyme binding functhon. Classification of the Hilit according to the BP of 58 therapeutic targets,the first place was the blood,followed by the lymph,the cerebrospinal fluid and digestive juice. It was found that the expression of some targets located in the skin was closed to the heart muscle,lymph node,spleen,cerebral cortex and so on,which were the main places for Hilit. In particular,ESR1,PTGS2,PPARA,PPARG,PTGS1 and CA2 were regulated by the flavonoids（ kaempferide and isorhamnetin）. The in vitro melanin production model showed that kaempferide and isorhamnetin could promote the melanin production in C57 BL/6 mice ear skin. Based on admet SAR and b SDTNBI,we used network pharmacological method to construct a systematic means of studying anti-vitiligo Uyghur medicines,providing clues for the further study of the modern molecular mechanisms of Phlegmatic temperament.