山沉香总木脂素抗肝癌的药效评价及网络药理学机制  

Evaluation of the Pharmacological Efficacy and Network Pharmacological Mechanisms of Total Lignans of Syringae Ramuls Against Liver Cancer

作　　者：任妍慧 渠成 白图雅 吕晓丽 刘云霞 范蕾 REN Yanhui;QU Cheng;BAI Tuya(School of Pharmacy,Inner Mongolia Medical University,Inner Mongolia 010110,China)

机构地区：[1]内蒙古医科大学药学院,呼和浩特010110 [2]内蒙古自治区新药筛选工程研究中心,呼和浩特010110

出　　处：《医学研究杂志》2025年第3期95-102,136,共9页Journal of Medical Research

基　　金：内蒙古自治区自然科学基金资助项目(2021MS08155);内蒙古医科大学面上项目(YKD2021MS041)。

摘　　要：目的利用体外细胞实验、网络药理学方法及分子对接技术探讨山沉香总木脂素(total lignans of syringae ramuls,TLS)抗肝癌的作用和潜在机制。方法采用流式细胞术检测TLS对HepG2细胞凋亡和周期的影响。通过文献检索收集TLS成分;通过ADMETlab评估成分的类药性和合成得分;通过ProTox-Ⅱ预测成分毒理学参数;通过Swiss Target Prediction网站预测TLS成分靶点;采用GeneCards、OMIM、DisGeNET和PharmGKB数据库筛选肝癌相关靶点;利用Cytoscape软件构建“成分-疾病-靶点”网络图和STRING平台构建交集靶点“蛋白质-蛋白质相互作用”(protein-protein interaction,PPI)网络图;使用DAVID数据库进行GO、KEGG和WIKI代谢通路分析。结果50~200μg/ml的TLS能够有效抑制HepG2细胞增殖,诱导细胞凋亡并阻滞细胞周期。TLS抗肝癌主要成分为罗汉松脂素、开环异落叶松树酯酚和羽叶丁香A等31个活性成分,主要作用于Akt1、Bcl-2、EGFR等82个关键靶点,抗肝癌机制与癌症通路、EGFR酪氨酸激酶抑制剂耐药、周期和凋亡等信号通路密切相关。结论TLS可能通过多成分、多靶点、多途径发挥抗肝癌作用。Objective To explore the effect and potential mechanism of total lignans of syringae ramuls(TLS)against liver cancer using in vitro cellular assays,network pharmacological and molecular docking.Methods Flow cytometry was performed to detect the effect of TLS on apoptosis and cycle of HepG2 cells.TL components were collected by literature search;drug-like properties and synthetic scores of components were assessed by ADMETlab;toxicological parameters of components were predicted by ProTox-Ⅱ;TLS component targets were predicted by Swiss Target Prediction website;GeneCards,OMIM,DisGeNET,and PharmGKB databases were used to screen the related targets of liver cancer;The"component-disease-target"network diagram was constructed by Cytoscape software and the"protein-protein interaction"(PPI)network diagram was constructed by STRING platform;and DAVID database was used to analyse GO,KEGG and WIKI metabolic pathways.Results TLS at 50-200μg/ml could significantly inhibit the proliferation of HepG2 cells,induce apoptosis and block the cell cycle.The main components of TLS in anti-liver cancer were 31 active components,such as(-)matairesinol,(-)-secoisolariciresinol,and pinnatifolin A,which mainly acted on 82 key targets such as Akt1,Bcl-2 and EGFR,which were mainly enriched in the cancer pathway,EGFR tyrosine kinase inhibitor resistance,cycle and apoptosis signaling pathways.Conclusion TLS may play an anti-liver cancer effect through multi-components,multi-targets,and multi-pathway.

关 键 词：网络药理学 山沉香总木脂素 肝癌 流式细胞术 分子对接技术 

分 类 号：R273[医药卫生—中西医结合]