目的 运用网络药理学和分子对接方法探究黄精抗肝细胞癌的潜在作用机制。方法 通过BATMAN-TCM 2.0、GeneCards、OMIM等数据库获取黄精活性成分靶点及肝细胞癌相关靶点，筛选交集靶点后构建蛋白质相互作用（PPI）网络，识别核心靶点。利用DAVID数据库进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析，挖掘关键生物过程和信号通路。结合GEO、GEPIA2等数据库进行单基因差异表达和生存分析，筛选关键基因。通过PDB数据库获取关键靶点蛋白三维结构，利用AutoDockTools软件进行黄精活性成分与靶点的分子对接，分析结合能。结果 共获得478个黄精与肝细胞癌交集靶点，核心靶点涉及肿瘤蛋白p53（TP53）、蛋白激酶B1（Akt1）、表皮生长因子受体（EGFR）等关键调控因子。GO富集显示靶点主要参与跨膜离子转运、细胞应激反应等生物过程；KEGG通路富集到193条通路，其中抑制磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（Akt）/哺乳动物雷帕霉素靶蛋白（mTOR）、丝裂原激活的蛋白激酶（MAPK）、Wnt通路为关键通路。单基因分析显示人雌激素受体1（ESR1）、丝裂原活化蛋白激酶3（MAPK3）、基质金属蛋白酶9（MMP9）在肝细胞癌中表达异常且与预后相关。黄精主要活性成分可能为黄芩素、甘草苷、去甲乌药碱等。分子对接证实其与核心靶点结合能均小于−5.0 kcal/mol，部分小于−7.0 kcal/mol，结合活性较强。结论 黄精通过多靶点（如TP53、Akt1、EGFR）调控PI3K/Akt/mTOR、MAPK、Wnt等信号通路抑制肝细胞癌增殖、诱导凋亡并干预转移过程。

Objective To explore the potential mechanism of Polygonatum sibiricum against hepatocellular carcinoma based on network pharmacology and molecular docking. Methods The active ingredient targets of P. sibiricum and hepatocellular carcinoma related targets were obtained from databases such as BATMAN-TCM 2.0, GeneCards, OMIM, etc. After screening for intersecting targets, a protein-protein interaction (PPI) network was constructed to identify core targets. Perform gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis using the DAVID database to identify key biological processes and signaling pathways. Combined with GEO, GEPIA2 and other databases, single gene differential expression and survival analysis were performed to screen key genes. Obtain the three-dimensional structure of key target proteins from the RCSB PDB database, and use AutoDockTools software to perform molecular docking between the active ingredients of P. sibiricum and the targets, analyzing the binding energy. Results A total of 478 intersecting targets between P. sibiricum and hepatocellular carcinoma were obtained, with core targets involving tumor protein p53 (TP53), protein kinase B1 (Akt1), and epidermal growth factor receptor (EGFR). GO enrichment showed that the target was mainly involved in biological processes such as transmembrane ion transport and cell stress response. The KEGG pathway was enriched to 193 pathways, among which the inhibition of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK), and Wnt pathway were the key pathways. Single gene analysis showed that human estrogen receptor 1 (ESR1), mitogen-activated protein kinase 3 (MAPK3), and matrix metalloproteinase 9 (MMP9) were abnormally expressed in hepatocellular carcinoma and were associated with prognosis. The main active components of P. sibiricum may be baicalein, liquiritin, higenamine, etc. Molecular docking confirmed that the binding energy with the core target was less than − 5.0 kcal/mol, some less than −7.0 kcal/mol, and the binding activity was strong. Conclusion P. sibiricum inhibits proliferation, induces apoptosis and interferes with metastasis of hepatocellular carcinoma by regulating PI3K/Akt/mTOR, MAPK, Wnt and other signaling pathways through multiple targets (such as TP53, Akt1, EGFR).

R285

湖北省中医药管理局中医药科研项目（ZY2023M036）