狼毒水煎液治疗H22肝癌小鼠的作用与机制  

The anti-tumor activity of Euphorbia fischeriana Steud based on network pharmacology and experimental verification

作　　者：闫桂溪 杜金城 杜钢军[1] YAN Guixi;DU Jincheng;DU Gangjun(Pharmaceutical College of Henan University,Kaifeng 475004,China;College of Traditional Chinese Medicine,Hunan University of Chinese Medicine,Changsha 410208,China)

机构地区：[1]河南大学药学院药物研究所,河南开封475004 [2]湖南中医药大学中医学院,长沙410208

出　　处：《河南大学学报（医学版）》2021年第1期7-14,共8页Journal of Henan University:Medical Science

基　　金：河南省自然科学基金(182300410310)。

摘　　要：[目的]观察狼毒抗肿瘤活性,并运用网络药理学预测狼毒可能的抗肿瘤成分与靶点。[方法]网络药理学分析狼毒抗肿瘤成分、作用靶点和通路;皮下移植小鼠模型评价狼毒对肿瘤生长的影响;二甲苯诱导耳肿胀评价狼毒对荷瘤小鼠炎症的影响;伊文思蓝渗透性评价小鼠瘤组织血管通透性;断尾法和毛细管法评价荷瘤小鼠凝血功能。[结果]网络药理学口服生物利用度OB≥30%、类药性DL≥0.18,筛选出狼毒6个活性成分,TCMSP、SWISS、STITCH预测得到109个靶点,与TTD比对得到26个癌症治疗靶点,参与84个生物过程和44个KEGG通路,其中的关键成分为胡萝卜苷、豆甾醇、β-谷甾醇。实验结果表明狼毒水煎液对H22皮下瘤生长有明显抑制作用(P<0.05),能显著降低二甲苯诱导的荷瘤小鼠耳肿胀(P<0.05)和肿瘤组织血管通透性(P<0.05),改善小鼠凝血功能(P<0.05)。[结论]狼毒的抗肿瘤作用与胡萝卜苷、豆甾醇、β-谷甾醇等组份抑制"PI3K-Akt信号传导""NF-κB"等信号通路减轻炎症、改善凝血功能有关。[Objective]To observe the anti-tumor components and targets of Euphorbia fischeriana Steud by network pharmacology and verify its anti-tumor activity.[Methods]Network pharmacology was used to analyze the possible anti-tumor components,action targets and pathways of Euphorbia fischeriana Steud.Effect of Euphorbia fischeriana Steud.on tumor growth was evaluated using H22 subcutaneously transplanted tumor model in mice,effect of Euphorbia fischeriana Steud.on inflammation was examined by ear edema in tumor bearing mice,the vascular permeability of tumor tissue was evaluated by Evans blue permeability,the coagulation was evaluated by capillary method and tail cutting method.[Results]6 active components with OB≥30%and DL≥0.18 were selected in TCMSP and 109 predicted targets were obtained by data of TCMSP,SWISS and STITCH.26 cancer therapeutic targets were confirmed in TTD,which involve in 84 GO(gene ontology)biological process and 44 KEGG(Kyoto Encyclopedia of Genes and Genomes)pathways.Beta-Sitosterol,Daucosterol,Stigmasterol were key components.Euphorbia fischeriana Steud showed an anti-tumor effect on H22 liver carcinoma in mice(P<0.05)and obviously decreased xylene-induced ear edema in tumor-bearing mice(P<0.05),improved vascular permeability in tumor tissues(P<0.05)and coagulation in tumor-bearing mice(P<0.05).[Conclusion]The anti-tumor activity of Euphorbia fischeriana Steud is possiblely related to Beta-Sitosterol,Daucosterol,Stigmasterol which suppress"NF-κB signaling pathway","API3 K-Akt signaling pathway"to prevent inflammation,improve coagulation function.

关 键 词：网络药理学 狼毒 肝癌 炎症 凝血 

分 类 号：R285.5[医药卫生—中药学]