肝细胞癌是全球发生率不断增加的最致命且最复杂的恶性肿瘤之一，被归类为第三大最常见的导致癌症相关死亡的原因和第六大最常见的新生物。从印度穿心莲中提取的一种活性植物成分 - 双萜类化合物穿心莲酮，传达用于缓解多种人类疾病，包括各种肿瘤。然而，穿心莲酮对肝细胞癌的抗肿瘤作用的分子机制仍然存在怀疑和不清楚的问题，这成为研究者和肿瘤学家面临的新挑战。本研究旨在通过综合网络药理学方法，分析穿心莲酮对肝细胞癌的潜在药理机制。在这里，我们采用网络药理学策略来研究潜在的肝细胞癌靶点。穿心莲酮靶点和肝细胞癌靶点被从多个数据库中提取。共获取到162个潜在的穿心莲酮与肝细胞癌重叠靶点，并进一步使用OmicsBox和DAVID数据库进行基因本体论和通路富集分析。随后，通过Cytoscape软件构建蛋白质相互作用网络，鉴定出前10个重要节点，并通过生存和表达分析进行验证。此外，通过CB-Dock2服务器和Desmond模块（Schrodinger软件）的分子对接和动力学模拟结果表明，白蛋白（ALB）、细胞周期蛋白D1（CCND1）、低氧诱导因子1α（HIF1A）、肿瘤坏死因子（TNF）和血管内皮生长因子（VEGFA）被确认为穿心莲酮的潜在靶点，具有较高的结合亲和力和良好的复合物稳定性。我们的研究不仅揭示了穿心莲酮的抗癌作用，还为穿心莲酮在肝细胞癌治疗中的抗肿瘤临床应用提供了新的见解，并将上述鉴定的靶点作为科学基础。此研究由Ramaswamy H. Sarma通讯。

HepatoCellular Carcinoma, being one of the most mortally convoluted malignancy with mounting number of occurrences across the world and being classified as the third most prevalent cause of cancer-associated mortalities and sixth most prevalent neoplasia. The active phytoconstituent andrographolide, derived from Andrographis paniculata is conveyed to reconcile a number of human ailments including various oncologies. However, the molecular mechanism underlying the anti-oncogenic effects of Andrographolide on HCC remains skeptical and unclear, emerging as a budding challenge for researchers and oncologists. The present study intends to analyze the underlying pharmacological mechanism of Andrographolide over HCC, established via assimilated approach of network pharmacology. Herein, the Network pharmacology stratagem was instigated to investigate potential HCC targets. The Andrographolide targets along with HCC targets were extracted from multiple databases. A total of 162 potential overlapping targets among HCC and Andrographolide were obtained and further subjected to gene ontology and Pathway enrichment analysis by employing OmicsBox and DAVID database, respectively. Subsequently, Protein-protein interaction network construction by Cytoscape software identified the top 10 hub nodes which were validated by survival and expression analysis. Further, the results derived from molecular docking and dynamic simulations by CB-Dock2 server and Desmond module (Schrodinger software) indicate ALB, CCND1, HIF1A, TNF, and VEGFA as potential Andrographolide related targets with high binding affinity and promising complex stability. Our findings not only reveal the antioncogenic role of andrographolide but also provide novel insights illuminating the identified targets as scientific foundation for anti-oncogenic clinical application of andrographolide in HCC therapeutics.Communicated by Ramaswamy H. Sarma.