基于网络药理学的杜仲不同部位功效及物质基础比较研究

杜仲皮、杜仲叶和杜仲雄花均来源于杜仲,三者在成分构成、药理作用方面的差异尚不明确。然而阐明杜仲不同部位的作用功效差异对于杜仲产品的开发具有重大的意义,而这种差异功效对应的物质基础也为不同部位的质量控制提供了依据。为了探讨杜仲不同部位的作用功效差异,该研究以不同部位的化学成分为研究对象,采用化合物靶标预测和靶标分析的策略,探讨杜仲(皮)、杜仲叶和杜仲花在药理作用方面的差异。其次为了阐明导致不同部位功效差异的物质基础,该研究通过构建"成分-靶标-功能"的关联网络,挖掘特异性功效对应的不同部位特异性成分,探讨导致功效差异的物质基础。根据靶标预测以及功能分析,杜仲可能的药理作用集中在抗氧化、神经调控、血压调控、心肌收缩、抗凋亡等。而杜仲的不同部位作用存在差异,杜仲叶特异性地参与成骨细胞分化、骨矿化等涉及骨发育的过程,此外还可能通过调控维生素D的代谢影响钙的吸收进而影响骨发育等过程。杜仲叶还可能特异性地作用于雌激素受体参与的雌激素及雌二醇的应答等过程。而关于肝脏的保护功能,杜仲叶可能通过调控维生素A相关的通路来发挥作用。相较于杜仲叶而言,杜仲(皮)特异性的药理作用可能是与泌尿系统的发育相关。杜仲雄花特异性参与疼痛的感受、谷氨酸信号通路以及兴奋性突出后电位等过程有关的功能。基于"成分-靶点-通路"的层次网络发现,杜仲不同部位特异性的功效与其特异性的化学成分密切相关,其中杜仲叶中特有的苯丙素类、萜类、环烯醚萜类、黄酮类及其他类成分靶向作用于杜仲叶特异性的功能,而杜仲(皮)中的黄酮类成分以及杜仲花中的萜类成分则可能是发挥它们特异性功效的物质基础。该研究中针对于杜仲不同部位的作用预测为后续杜仲产品开发的侧重点和差异性提供了新的依据;同时基于差异化功效的物质基础研究也为杜仲差异化产品的质量控制提供了依据。

Possible pharmaceutical effect and active components in different parts of Eucommia ulmoides based on network pharmacology

The difference in pharmacological activities and active components between leaves, barks and flowers of Eucommia ulmoides(EU) are still unclear. However, clarifying the differences in pharmacological effects of different parts of EU is of great significance for the development of EU products, and their corresponding active components provide basis for quality control of different parts of EU. Based on the chemical compositions of different parts of EU, integrated strategy of target prediction and target analysis of the compounds was used to investigate the difference in the pharmacological effects of leaves, barks and followers. The "component-target-function" association network was constructed to mine the specific material basis corresponding to specific efficacy of different parts of EU. In this study, the author found that EU may have the activities of anti-oxidation, neuromodulation, blood pressure regulation, myo-cardial expansion, and anti-apoptosis according to target prediction and function analysis. However, the effects of different parts of EU were different. Leaves were involved in the process of bone development such as osteoblast differentiation and bone mineralization in a specific way. In addition, the leaves may affect the process of bone development by regulating the metabolism of vitamin D and affecting the absorption of calcium. Leaves may also specifically act on estrogen and estradiol response processes where estrogen receptors were involved. Regarding its protective function for the liver, leaves may play a role by regulating vitamin A-related pathways. As compared with leaves, the specific pharmacological effects of barks may be related to the development of the urinary system. Flowers specifically participate in functions related to pain sensation, glutamate signaling pathway, and excitatory postsynaptic potential. Based on the hie-rarchical network of "component-target-pathway", we further found that specific activities of different parts of EU were inseparable from its specific chemical compositions. Phenylpropanoids, terpenoids and rings, iridoids, flavonoids and other components which are specific in leaves can target the specific effects of leaves, while the flavonoids in barks and the quinones in flowers may be the material basis for their respective specific effects. The prediction of the activities of different parts of EU provides a new basis for the focuses and differences in subsequent Eucommia product development. At the same time, the material basis research based on differential efficacy also provides a basis for the quality control of Eucommia differentiated products.