甘遂与甘草反药相互作用的网络药理学分析

Network Pharmacology on Interaction of Effective or Toxic Components of Kansui Radix and Glycyrrhizae Radix et Rhizoma

目的:采用网络药理学方法,探讨甘遂和甘草反药配伍后药效/毒性成分的分子作用机制,分析其多成分-多靶点-多通路相互关系。方法:针对甘遂甘草的主要药效/毒性成分——甘遂萜酯A,甘遂萜酯B,甘遂萜酯C,甘草酸,甘草苷,异甘草苷和刺芒柄花素,依据Pharm Mapper数据库构建多成分-蛋白网络,获取的靶点信息利用博奥数据库MAS 3.0系统得到相应通路,通过Cytoscape软件建立成分-靶点-通路网络模型。结果:网络分析表明,甘遂、甘草配伍药效/毒性成分涉及神经-免疫-内分泌-泌尿等相关的61条通路。在调节水和电解质排泄方面药效相反,与肾素血管紧张素系统、类固醇生物合成等通路有关;在抗肿瘤、抗炎、调节免疫方面发挥协同作用,涉及33条通路;两者配伍存在基于肝药酶代谢的毒性增强现象。结论:甘遂与甘草配伍存在药效降低或药效协同和毒性改变等多种情况,体现了中药配伍多成分、多靶点、多途径作用模式,该研究为深入探讨甘遂甘草配伍的分子作用机制提供了参考。

Objective： To explore the molecular mechanisms of effective or toxic components of Kansui Radix and Glycyrrhizae Radix et Rhizoma by using network pharmacology method, and to investigate the correlations between multi-compounds,multi-targets and multi-pathways. Method： The main effective or toxic components of Kansui Radix and Glycyrrhizae Radix et Rhizoma, including kansuinine A, kansuinine B,kansuinine C,gycyrrhizic acid,liquiritin,isoliquiritin,formononetin were collected to build multi-componentsproteins networks based on Pharm Mappear database. The obtained targets information was used to obtain corresponding pathways by using Boao MAS 3. 0 system, and then Cytoscape software was used to construct components-targets-pathways network model. Result： The network analysis showed that,action of the effective or toxic components of Kansui Radix and Glycyrrhizae Radix et Rhizoma involved 61 pathways related to nerveimmune-endocrine-urinary. Contrary to their efficacy in adjusting water and electrolyte excretion,they were related with renin-angiotensin system,steroids biosynthesis and other pathways. Kansui Radix and Glycyrrhizae Radix et Rhizoma had synergistic effects in anti-tumor,anti-inflammatory and immune regulation,covering 33 pathways.Compatibility of Kansui Radix and Glycyrrhizae Radix et Rhizoma would enhance toxicity concerned to inhibition or induction of hepatic drug enzyme. Conclusion： Compatibility of Kansui Radix and Glycyrrhizae Radix et Rhizoma could result in decreased or synergistic effect and would change the toxicity. This reflected the compatibility mode of multi-compounds,multi-targets and multi-pathways for traditional Chinese medicines. It may provide reference for deeper study on molecular mechanism of compatibility of Kansui Radix and Glycyrrhizae Radix et Rhizoma.