山西医科大学学报2025,Vol.56Issue(11):1199-1209,11.DOI:10.13753/j.issn.1007-6611.2025.11.001
基于网络药理学和体外实验探讨罗汉果皂苷Ⅴ对肝细胞癌的作用机制
Mechanism of Mogroside Ⅴ against hepatocellular carcinoma through network pharmacology and in vitro experiments
摘要
Abstract
Objective To explore the mechanisms of Mogroside Ⅴ(MⅤ)against hepatocellular carcinoma(HCC)based on network pharmacology and in vitro experiments.Methods Potential targets of MⅤ against HCC were screened by network pharmacology.The protein-protein interaction(PPI)network was constructed with the STRING database,and the core targets were screened by Cytoscape.Enrichment analysis of potential targets was performed on the DAVID database.AutoDock software was used for molecular docking between MⅤ and core targets.Human HCC cells HepG2 and Huh7 were treated with different concentrations(0-200 μmol/L)of MⅤ,and the half maximal inhibitory concentrations(IC₅₀)of MⅤ extract to HepG2 and Huh7 cells were calculated using CCK-8 assay.HepG2 and Huh7 cells were divided into control group(0 μmol/L MⅤ)and MⅤ group(30 μmol/L MⅤ for HepG2,20 μmol/L MⅤfor Huh7)based on IC₅₀ results.Cell proliferation ability was detected by plate cloning experiment.Cell apoptosis and cell cycle were analyzed by flow cytometry.The protein expression levels of genes related to epithelial-mesenchymal transition(EMT),including E-cadherin,N-cadherin and Vimentin,were measured by Western blot.And the mRNA expression levels of genes related to the NF-κB signaling pathway,including TNF-α,IL-6,IL-1β and NF-κB1,were detected by real-time quantitative reverse transcription poly-merase chain reaction(RT-qPCR).Results A total of 162 potential targets for MⅤ against HCC were identified,with eight core targets(TNF,ALB,IL-6,IL-1β,STAT3,NF-κB1,CASP3,and SRC).Molecular docking demonstrated a high binding affinity between MⅤ and all core targets.The IC₅₀ of MⅤ was(33.22±1.39)μmol/L for HepG2 cells and(23.79±2.51)μmol/L for Huh7 cells.Compared with control group,HepG2 and Huh7 cells in MⅤ group showed decreased cell proliferation activity(P<0.001),and increased apoptosis rates(P<0.05).Furthermore,both HepG2 and Huh7 cells exhibited a decreased proportion of cells in the G0/G1 phase and an increased proportion in the G2/M phase(all P<0.001).Western blot results of HepG2 and Huh7 cells showed that compared with control group,the protein expression level of E-cadherin was increased in MⅤ group,while the protein expression levels of N-cadherin and Vimentin were decreased(all P<0.05).RT-qPCR results of HepG2 and Huh7 cells showed that,compared with control group,the mRNA expression levels of TNF-α,IL-6,IL-1β,and NF-κB1 were all decreased in MⅤ group(all P<0.001).Conclusion MⅤmay exert its inhibitory effect on HCC by suppressing the NF-κB signaling pathway through targeting TNF-α,IL-6,IL-1β,NF-κB1,and other genes.关键词
罗汉果皂苷Ⅴ/肝细胞癌/网络药理学/分子对接/细胞实验/NF-κB信号通路Key words
Mogroside Ⅴ/hepatocellular carcinoma/network pharmacology/molecular docking/cell experiments/NF-κB signaling pathway分类
医药卫生引用本文复制引用
LIU Siqin,HUANG Xiyang,TANG Hui,TAN Yanjun,GAN Xiang,LI Hongtao,YANG Xiaoli..基于网络药理学和体外实验探讨罗汉果皂苷Ⅴ对肝细胞癌的作用机制[J].山西医科大学学报,2025,56(11):1199-1209,11.基金项目
广西自然科学基金重点研发计划项目(桂科AB17195006) (桂科AB17195006)
广西自然科学基金面上项目(2021JJA140230) (2021JJA140230)
广西高校中青年教师科研基础能力提升项目(2025KY0530) (2025KY0530)