Wang Ji-Ye, Wang Xiao-Qin, Tang Yun, Zhang Bo
Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, School of Pharmacy, Shihezi University, Shihezi 832002, China.
Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200082, China.
Zhongguo Zhong Yao Za Zhi. 2018 May;43(9):1780-1788. doi: 10.19540/j.cnki.cjcmm.2018.0061.
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 admetSAR. The targets of active compounds were predicted via bSDTNBI (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-targets-BP-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 C57BL/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 C57BL/6 mice ear skin. Based on admetSAR and bSDTNBI, 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.
基于痰湿体质理论探讨四种维吾尔族白癜风治疗药物的网络药理学机制。首先，收集基于痰湿体质理论的维吾尔族白癜风治疗药物方剂。利用admetSAR获取四种维吾尔族白癜风治疗药物中主要化合物的药代动力学特征。通过bSDTNBI（基于平衡子结构-药物-靶点网络的推断模型）方法预测活性化合物的靶点。然后，通过DAVID数据库对靶点进行生物学过程（BP）和分子功能（MF）富集分析。构建维吾尔族白癜风治疗药物方剂-维吾尔族药物网络模型（FMI网络）和维吾尔族药物-活性化合物-靶点-BP-Hilit网络模型（MCTBHI网络），利用接近中心性分析关键维吾尔族药物、活性化合物、关键靶点以及Hilit。最后，采用C57BL/6小鼠体外黑色素生成模型验证活性化合物改善黑色素生成的能力。结果表明，补骨脂、驱虫斑鸠菊、丁香和白菖蒲是FMI网络中的关键维吾尔族药物。有22种生物利用度相对较高的活性化合物与58个治疗靶点相互作用。这些活性化合物主要由香豆素类和黄酮类组成。在MCTBHI网络中，58个治疗靶点的MF与类固醇激素受体活性、血红素结合和酶结合功能有关。根据58个治疗靶点的BP对Hilit进行分类，首位是血液，其次是淋巴、脑脊液和消化液。发现一些位于皮肤的靶点的表达与心肌、淋巴结、脾脏、大脑皮层等Hilit的主要部位相近。特别是，ESR1、PTGS2、PPARA、PPARG、PTGS1和CA2受黄酮类化合物（山柰酚和异鼠李素）调控。体外黑色素生成模型表明，山柰酚和异鼠李素可促进C57BL/6小鼠耳部皮肤黑色素生成。基于admetSAR和bSDTNBI，我们采用网络药理学方法构建了一种系统的研究维吾尔族白癜风治疗药物的手段，为进一步研究痰湿体质的现代分子机制提供线索。
