基于网络药理学研究厚朴温中汤治疗脾胃虚寒型胃病的潜在靶点和机制  

Potential targets and mechanism of Houpuwenzhongtang for the treatment of spleen and stomach deficiency cold stomach disease based on network pharmacology

作　　者：蒋红霞 陈婉君 许炜炜 马勤阁 孙群 陈殊 刘建群 JIANG Hong-xia;CHEN Wan-jun;XU Wei-wei;MA Qin-ge;SUN Qun;CHEN Shu;LIU Jian-qun(Key Laboratory of Modern Preparation of TCM,Ministry of Education,Jiangxi University of Chinese Medicine,Nanchang 330004,China)

机构地区：[1]江西中医药大学现代中药制剂教育部重点实验室,江西南昌330004

出　　处：《中国药理学通报》2023年第9期1764-1773,共10页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 82160731)。

摘　　要：目的探究厚朴温中汤治疗脾胃虚寒型胃病的潜在靶点和机制。方法运用TCMSP数据库、疾病数据库和化合物靶点预测平台,收集活性成分、疾病靶点,预测潜在作用靶点;应用Cytoscape 3.7.2和String平台进行关键化学成分和核心靶点筛选,构建PPI网络图;将degree值大于30的活性成分与关键靶点进行分子对接,并进行细胞实验。结果厚朴温中汤治疗脾胃虚寒型胃病的关键活性成分包括橙皮苷、厚朴酚、6-姜辣素等;关键靶点包括JUN、AKT1、IL-8等;相关通路主要涉及免疫应答、信号转导、细胞增殖与凋亡等;分子对接显示关键活性成分与关键靶点结合活性较好。细胞实验结果显示,厚朴酚、橙皮苷、6-姜辣素均对IL-8有很好的抑制作用,且呈剂量依赖关系。结论推测厚朴温中汤可能通过关键活性成分作用于关键靶点,参与PI3K-AKT、NF-κB等信号通路调控,实现治疗脾胃虚寒型胃病相关疾病作用;首次发现6-姜辣素能够与多个治疗脾胃虚寒型胃病的疾病靶点(如AKT1、IL-8等)稳定结合,提示6-姜辣素值得进一步研究;根据IL-8细胞实验结果,推测厚朴酚、橙皮苷、6-姜辣素可能通过降低胃黏膜中IL-8含量,对幽门螺杆菌感染引起的胃病产生作用。Aim To explore the potential targets and mechanisms of Houpuwenzhongtang for the treatment of spleen and stomach deficiency cold stomach disease.Methods Firstly,TCMSP database,disease database and compound target prediction platform were used to collect active components,disease targets and predict potential targets.Secondly,Cytoscape 3.7.2 and String platform were used to screen key chemical components and core targets,and PPI network diagram was constructed.Finally,The active components with degree greater than 30 were used for molecular docking with key targets,and some docking results were selected for cell experiment.Results The key active components of Houpuwenzhongtang in the treatment of spleen and stomach deficiency cold stomach disease were hesperidin,magnolol,6-gingerol,and so on.The key targets were JUN,AKT1,IL-8,etc..The related pathways mainly involved immune response,signaling transduction,cell proliferation and apoptosis.Molecular docking results showed that the key active components had good binding activity with disease targets.The results of cell experiments showed that magnolol,hesperidin and 6-gingerol had different degrees of anti-inflammatory activity against IL-8 in a dose-dependent manner.Conclusions It is speculated that Houpuwenzhongtang may act on IL-8,JUN,AKT1 and other targets through magnolol,hesperidin,6-gingerol and other active ingredients,and participate in the regulation of PI3K-AKT signaling pathway,NF-κB signaling pathway for the treatment of spleen and stomach deficiency cold stomach disease.And it is found for the first time that 6-gingerol could stably bind to multiple disease targets related spleen and stomach deficiency cold stomach disease,such as AKT1,IL-8 and so on.The result suggests that 6-gingerol is worth further research.Through the results of IL-8 cell experiment,it is speculated that the components such as magnolol and hesperidin may play a role in gastric diseases caused by Helicobacter pylori infection by reducing the content of IL-8 in gastric mucosa.

关 键 词：网络药理学 厚朴温中汤 脾胃虚寒型胃病 分子对接 细胞验证 潜在靶点和机制 

分 类 号：R319[医药卫生—基础医学] R256.39R289.5R573.3