Study on possible synergistic anticancer cachexia effects of the main active compounds of Radix Sophorae flavescentis  

作　　者：Hong Zhang Lin-Lin Chen Meng-Yi Chi Xi-Peng Sun Quan-Jun Yang Li-Li Wan Cheng Guo 

机构地区：[1]Department of Pharmacy,Shanghai Jiao Tong University Affiliated Shanghai Sixth People’s Hospital,Shanghai 200233,China [2]School of Medicine,Shanghai Jiao Tong University,Shanghai 200240,China [3]School of Pharmacy,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China

出　　处：《Traditional Medicine Research》2021年第4期46-61,共16页TMR传统医学研究

基　　金：the National Natural Science Foundation of China(No.81873042,81872494 and 81803633).

摘　　要：Background:Cancer cachexia is a complex disease secondary to cancer,and no specific therapy for it has been found.The Chinese herb Kushen(Radix Sophorae flavescentis)is the dried root of Sophora flavescens Aiton,which has been widely applied in treating digestive and urinary inflammatory diseases.Matrine,one of the main components of Radix Sophorae flavescentis,can alleviate cancer cachexia.Methods:Compounds from Radix Sophorae flavescentis were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.The targets related to cancer cachexia were queried from the Therapeutic Target Database(http://db.idrblab.net),DisGeNET database(http://www.disgenet.org),and Search Tool for Interacting Chemicals database,related literature,and constructed cancer cachexia-protein network.Cancer cachexia-protein network was merged with compound-protein networks respectively using Cytoscape software as well as network topology data and key targets counting.Pathway enrichment analysis was conducted via the Database for Functional Annotation Bioinformatics Microarray Analysis.Protein crystal structures and compound structures were queried from RCSB and PubChem databases,respectively.Molecular docking was conducted using Discovery Studio software.Results:The anticancer cachexia compounds of Radix Sophorae flavescentis were screened as oxymatrine,matrine,and kurarinol,and targets such as BIRC2,TNF and STAT3 were found.The mechanisms of oxymatrine,matrine,and kurarinol have the characteristics of synergy and complementarity.Kurarinol has a mechanism similar to that of matrine,which includes the FoxO signaling pathway,insulin resistance and mTOR signaling pathway.TNF signaling pathway is a common signaling pathway of kurarinol,oxymatrine and matrine.Adipocytokine signaling pathway is the other common pathway of kurarinol and oxymatrine except for the TNF signaling pathway.Kurarinol can be successfully docked with CYCS,GPX2,BIRC7,etc.,and kushenol C can be successfully docked with IKBKB and PIK3CD.

关 键 词：Radix Sophorae flavescentisn Cancer cachexia Kurarinol MATRINE OXYMATRINE TNF signaling pathway 

分 类 号：R73[医药卫生—肿瘤]