目的 通过网络药理学和实验验证方法探讨雷公藤治疗黑色素瘤的活性成分、作用靶点及信号通路，分析雷公藤对黑色素瘤的作用机制。方法 通过TCMSP数据库检索雷公藤的有效成分及靶点，借助GeneCards、OMIM数据库获取中药与疾病的交集靶点。采用Cytoscape 3.7.1进行拓扑分析，构建“药物活性成分–疾病靶点”网络图。运用String平台构建共同靶点蛋白相互作用（PPI）网络和条形图，筛选出核心靶点。进行靶点基因富集分析，完成核心靶标与成分的分子对接。利用CCK-8及qPCR方法验证核心单体成分对黑色素瘤及治疗靶点的作用。结果 雷公藤有效成分51个，其中最优成分是雷公藤甲素、山柰酚。雷公藤甲素对黑色素瘤细胞具有明显抑制作用，且显著降低核心治疗靶点蛋白激酶B1（Akt1）、血管内皮生长因子A（VEGFA）的mRNA表达（P＜0.01、0.001）。结论 雷公藤治疗黑色素瘤具有多靶点、多通路的特点，其中雷公藤甲素是其核心药用成分，该研究为雷公藤抗黑色素瘤提供了实验依据。

Objective To predict the active ingredients, targets and signaling pathways of Tripterygium wilfordii in treatment of melanoma by network pharmacology and experimentation, and to analyze the mechanism of Tripterygium wilfordii in treatment of melanoma. Methods To search the active components and targets of Tripterygium wilfordii from TCMSP database, and the intersection targets of traditional Chinese medicine and diseases were obtained from GeneCards and OMIM databases. Topological analysis was carried out on Cytoscape 3.7.1 to construct the “drug active ingredients - disease targets” network diagram. The interaction network and bar graph of common target protein were constructed with String platform, and the core target was screened out. Target gene enrichment analysis was carried out to complete the molecular docking of core targets and components. CCK8 and qPCR methods were used to verify the effects of core monomer components on melanoma and therapeutic targets. Results There were 51 active components of Tripterygium wilfordii. The best ingredient are kaempferol and triptolide. It has a significant inhibitory effect on melanoma cells, and significantly reduces the mRNA expression of core therapeutic targets Akt1 and VEGFA. Conclusion Tripterygium wilfordii has the characteristics of multi-target and multi-pathway in treatment of melanoma, and triptolide is its core medicinal component. This study provides experimental basis for Tripterygium wilfordii anti-melanoma.

R979.1

河南省科技研发计划联合基金（优势学科培育类）项目（222301420060）；河南省自然科学基金-优秀青年科学基金项目（212300410057）