甘草次酸药物代谢动力学评价及其抗肝细胞癌机制研究

利用药物信息学技术研究甘草次酸的药物代谢动力学参数及抗肝细胞癌机制。在SwissADME服务器分析甘草次酸的药动学参数，运用TCMSP、Swiss TargetPrediction、PharmMapper、GeneCards、CTD数据库和STRING数据平台预测和筛选甘草次酸抗肝细胞癌靶点，并构建靶蛋白互作网络，运用OmicShare及DAVID v 6.8平台对靶点进行GO功能富集分析和KEGG通路分析。运用AutoDuck Vina软件对甘草次酸与核心靶点进行分子对接，分析二者间的亲和力。实验结果显示：甘草次酸符合类药五原则，具有较好的胃肠吸收性。甘草次酸主要作用于HSP90AA1、CTNNB1、SRC、TNF 4个核心靶点，与TNF的亲和力最大；参与细胞增殖、活性氧、类固醇激素、氧化应激等生物过程；重点调控VEGF信号通路、TNF信号通路、癌症通路和癌症蛋白聚糖，能够遏制细胞增殖、侵袭转移，以及抗炎、抗血管生成。因此甘草次酸成药性好，具有多靶点-多通路-多机制抗肝细胞癌活性，可作为潜在的抗肝细胞癌药物进一步研究。

EVALUATION OF PHARMACOKINETICS AND MECHANISM OF ANTI-HEPATOCELLULAR CARCINOMA OF GLYCYRRHETINIC ACID

To study the pharmacokinetic parameters and its mechanism of anti-hepatocellular carcinoma of glycyrrhetinic acid by using drug information technology. SwissADME server was used to analyze the pharmacokinetic parameters of glycyrrhetinic acid. TCMSP, Swiss TargetPrediction, PharmMapper, GeneCards, CTD databases and STRING platform predicted and screened the targets of glycyrrhetinic acid-anti-hepatocellular carcinoma and constructed protein-protein interaction network. OmicShare and DAVID v 6.8 platforms were used for GO functional enrichment analysis and KEGG pathway analysis. AutoDuck Vina software was used for molecular docking to analyze the affinity between glycyrrhetinic acid and the core targets. Glycyrrhetinic acid conforms to the five principles of pharmacoids and has good gastrointestinal absorption. Glycyrrhetinic acid mainly acts on four core targets of HSP90AA1, CTNNB1, SRC and TNF, has the highest affinity with TNF; it takes part in cell proliferation, reactive oxygen species, steroid hormones, oxidative stress and other biological processes, mainly regulates VEGF and TNF signaling pathways, cancer pathways and proteoglycans, which can inhibit cell proliferation, invasion and metastasis, as well as anti-inflammatory and anti-angiogenesis. Glycyrrhetinic acid is an ideal drug with multi-target-multi-pathway-multi-mechanism activities against hepatocellular carcinoma, which can be further studied as a potential anti-hepatocellular carcinoma drug.