用于妇科血瘀证原发性痛经的四物汤类方主要活性成分网络药理学分析

Network pharmacology study on major active compounds of Siwu decoction analogous formulae for treating primary dysmenorrhea of gynecology blood stasis syndrome

目的:采用网络药理学方法对用于妇科血瘀证原发性痛经的四物汤类方主要活性成分的分子作用机制分析,探索其多成分-多靶点-多通路相关关系。方法:针对类方中藁本内酯、正丁烯基酜内酯、川芎内酯、阿魏酸、没食子酸、芍药苷、焦地黄素A、梓醇等共有的活性成分及各方差异的代表性活性成分,依据PharmMapper数据库构建多成分-蛋白网络,获取的靶点信息利用Kyoto encyclopedia of genes and genomes(KEGG)通路数据库,采用Cytoscape软件建立四物汤类方成分-靶点-通路网络模型。结果与结论:网络分析表明,在细胞过程中起重要作用的丝氨酸苏氨酸蛋白激酶是四物汤及其类方共有的潜在作用靶点群;四物汤主要活性成分涉及神经-内分泌-免疫等相关的51条通路,除与四物汤相同的通路外,少腹逐瘀汤偏重于脂质代谢;香附四物汤偏重于氨基酸代谢通路;桃红四物汤偏重于碳水化合物代谢;芩连四物汤偏重于ErbB,VEGF信号转导通路。四物汤及衍化方既有共同的作用靶点及通路,又各有偏重,体现了方剂多成分、多靶点、多途径作用模式,该研究为深入研究四物汤类方分子作用机制提供线索。

Objective： To explore the molecular mechanisms of main active ingredients of Siwu decoction analogous formulae for treating primary dysmenorrhea of gynecology blood stasis syndrome by network pharmacology study, and to investigate the correlations between multi-compounds, multi targets and multi pathways. Method： Major active compounds from Siwu decoction analogous formulae, including ligustilide, butylidene phthalide, senkyunolide, ferulic acid, gallic acid, peoniflorin, jioglutin A, catalpol, transanethole, zingiberone, commiphoric acid, eugenol, isorhamnetin-3-O-neohesperidoside, wulingzhic acid, a-cyperone, cyperene, cost- unolide, costic acid, tetrahydropalmatine, protopine, amygdalin, 24-methylene cycloartanol, oleic acid, linoleic acid, 3-p-cou- maroylquinic acid, hydroxysafflor yellow A, coptisine, berberine, jatrorrhizine, baicalein, baicalin, wogonin were collected to build component-protein networks based on PharmMapper database. The targets information access was used to construct and visualize components-targets-pathways network model using the kyoto encyclopedia of genes and genomes （KEGG） pathway database and Cytoscape software. Result and Conclusion： Serine threonine protein kinases play an important role in the process of cells. They were potential targets in the effect of Siwu decoction analogous formulae. The effect of main active ingredients involved 51 the pathway. Besides the same ones, Shaofu Zhuyu decoction had more effect on lipid metabolism, Xiangfu Siwu decoction on amino acid metabolism pathways, Taohong Siwu decoction on carbohydrate metabolism, while, Qinlian Siwu decoction on ErbB, VEGF signal transduction pathway. Siwu decoction and its derived formulae not only had common targets and pathways, but also had their own emphasis. This reflected the for- mulae effect mode of multi-ingredients, multi-targets and multi-pathways. It may provide clues to deeper study of molecular mechanism of Siwu decoction analogous formulae action.