目的 通过网络药理学及分子对接探索柴胡皂苷d治疗鼻咽癌的作用机制。方法 通过SwissTargetPrediction、Stitch、GeneCards数据库预测柴胡皂苷d药物潜在的作用靶点，检索DrugBank、GeneCards、TTD、Omim、Pharmgkb数据库获得鼻咽癌靶点；使用R 4.3.1软件获取柴胡皂苷d和鼻咽癌的交集靶点。运用STRING数据库构建交集靶点的蛋白相互作用（PPI）网络；使用Cytoscape软件对STRING数据库筛选的靶点进一步筛选核心靶点；使用R 4.3.1软件“ClusterProfiler”包对柴胡皂苷d和鼻咽癌的交集靶点进行基因本体（GO）富集分析和京都基因与基因组百科全书（KEGG）通路富集分析，通过分子对接明确柴胡皂苷d治疗鼻咽癌的作用机制。结果 预测得到柴胡皂苷d靶点140个，筛选、去重得到鼻咽癌疾病靶点2 854个，最后得到交集靶点74个，得到信号转导及转录激活因子3（STAT3）、丝裂原活化蛋白激酶1（MAPK1）、肿瘤蛋白p53（TP53）、低氧诱导因子-1A（HIF-1A）、原癌基因（MYC）5个核心靶点。GO和KEGG富集分析结果显示，柴胡皂苷d可能通过磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（Akt）信号通路、MAPK信号通路、卡波西肉瘤相关疱疹病毒感染等通路起到治疗鼻咽癌的作用。分子对接结果显示柴胡皂苷d与核心靶点对接结合能均小于−7.7 kcal/mol。结论 柴胡皂苷d可通过多靶点和多通路的途径发挥治疗鼻咽癌的作用。

Objective To explore the mechanism of saikosaponin d in treatment of nasopharyngeal carcinoma through network pharmacology and molecular docking.Method The potential targets of the drug bupleuronate d were predicted through the SwissTartgetPrediction, Stitch, and GeneCards databases, and the nasopharyngeal carcinoma targets were obtained by searching the DrugBank, GeneCards, TTD, Omim, and Pharmgkb databases. The intersection target of saikosaponin d and nasopharyngeal carcinoma was obtained using R 4.3.1 software. STRING database were used to construct the PPI network of intersection targets. Cytoscape software was used to further screen the core targets from the targets screened in the STRING database. The intersection target of saikosaponin d and nasopharyngeal carcinoma was analyzed for GO enrichment and KEGG pathway enrichment using the “ClusterProfiler” package of R4.3.1 software. Mechanism of saikosaponin d in treatment of nasopharyngeal carcinoma was clarified through molecular docking.Result 140 Saikosaponin d targets were predicted, 2 854 nasopharyngeal carcinoma disease targets were screened and deduplicated, and finally 74 intersecting targets were obtained, including 5 core targets including STAT3, MAPK1, TP53, HIF1A, MYC, etc. The GO and KEGG enrichment analysis results showed that saikosaponin d may play a therapeutic role in nasopharyngeal carcinoma through pathways such as PI3K/Akt signaling pathway, MAPK signaling pathway, and Kaposi's sarcoma associated herpesvirus infection. The molecular docking results showed that the binding energy between saikosaponin d and the core target was less than −7.7 kcal/mol.Conclusion Saikosaponin d can exert therapeutic effects on nasopharyngeal carcinoma through multi-target and multi pathway pathways.

R285

广东医科大学青年科研培育基金（GDMUQ2022013）