基于系统药理学分析野生真菌硬皮马勃治疗肿瘤多层次作用机制  

Analysis of the Multi-level Mechanisms of Wild Fungus of Scleroderma sinnamariense Against Tumor Based on Systems Pharmacology

作　　者：李敏[1] 王宜磊[1] 高霞 周广灿 唐欣 张桂荣[1] 崔慧 Li Min;Wang Yilei;Gao Xia;Zhou Guangcan;Tang Xin;Zhang Guirong;Cui Hui(Key Laboratory of Microbiology,College of Agricultural and Biological Engineering,Heze University,Heze 274015,China;Shandong Agricultural Technology Extension Center,Jinan 250014,China)

机构地区：[1]菏泽学院农业与生物工程学院微生物重点实验室,菏泽274015 [2]山东省农业技术推广中心,济南250014

出　　处：《世界科学技术-中医药现代化》2022年第4期1603-1613,共11页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：山东省菏泽学院科研项目(XY17KJ07):珍稀大型真菌M-1菌株的ITS鉴定、培育和发酵动力学研究,负责人:李敏;山东省2019年度农业重大应用技术创新项目(SD2019ZZ014):秸秆栽培草腐菌设施周年绿色生产关键技术研究与示范,负责人:高中强。

摘　　要：目的鉴定当地民间应用普遍的野生药用真菌,并探讨其治疗肿瘤的作用机制。方法采用形态学和分子生物学方法对一株采自定陶仿山野生药用真菌进行鉴定,确定为硬皮马勃。通过文献检索收集硬皮马勃化学成分,利用PubChem软件和TCMSP、GCS数据库得到化学成分结构信息及其药用动力学参数和相关靶点分析,通过SysDT和WES系统鉴定潜在化学成分靶点,利用CTD数据库获得靶点功能,将潜在化合物和肿瘤相关靶点导入Cytoscape3.8.0软件构建分子-靶标网络。应用DAVID数据库对肿瘤相关靶点进行GO和KEGG富集分析,揭示有关活性成分靶点所涉及的生物学过程和通路,将肿瘤相关靶点和通路导入Cytoscape3.8.0软件构建靶点-通路网络。结果从文献中获得硬皮马勃的化学成分59个,通过ADME计算系统筛选出5个潜在活性的化合物即活性成分,预测到38个靶点,其中与肿瘤相关靶点16个。这些活性成分主要通过Toll-like receptor、PI3K-AKT、MAPK和NF-kappa B等通路参与免疫应答,抑制肿瘤细胞生长、增殖,促进其凋亡。结论表明硬皮马勃治疗肿瘤具有多靶点、多途径协同作用的特点,并通过多层次效应达到治疗肿瘤的效果。本研究为更好理解硬皮马勃作用肿瘤的机制和肿瘤药物开发提供理论依据。Objective To identify a wild medicinal fungal strain which has a widespread application in folk medicine and explore the action mechanisms against tumor.Methods A wild medicinal fungal strain collected from Fangshan in Dingtao district, Shandong Province was isolated, cultured and identified as Scleroderma sinnamariense by morphological and Internal Transcribed Spacer(ITS) methods. Ingredients of Scleroderma sinnamariense were screened through literatures. The structural information, medicinal kinetic parameters and related targets of Scleroderma sinnamariense was obtained through PubChem, Traditional Chinese Medicine System Pharmacology(TCMSP), Gene Cards Suite(GCS).The potential targets against tumor were screened by System Drug Target(SysDT) and Weighted Ensemble Similarity(WES). The target functions of Scleroderma sinnamariense were acquired from Comparative Toxicogenomics Database(CTD). The core targets and potential ingredients network of Scleroderma sinnamariense was established by Cytoscape.Thereafter, the biological processes and pathways against tumor were clearly displayed by integration of network analysis and function enrichment analysis of GO and KEGG which were performed using the DAVID database. Results 5candidate active ingredients of Scleroderma sinnamariense were obtained on the basis of ADME system from 59ingredients which were obtain from literature, and 38 targets were identified which included 16 pharmacological targets of tumor cell. Integrating network and enrichment analysis showed that the main active ingredients of Scleroderma sinnamariense could take part in immune response, inhibit growth, proliferation, and migration of tumor cell and induced apoptosis of tumor cell by Toll-like receptor, PI3K-AKT, MAPK and NF-kappa B signaling pathway, so as to achieve antitumor effect.Conclusion The main active ingredients of Scleroderma sinnamariense have characteristics of multitarget and multi-channel when they perform effect against tumor via multi-levels action. The study also provided a new

关 键 词：硬皮马勃 系统药理学 肿瘤 机制 

分 类 号：R285[医药卫生—中药学]