Tian Xinchen, Liu Fen, Zhao Jing, Liu Qingbin, Wang Haochen, Liu Yanmei, Zhang Jiaqi, Zhang Yiming, Yang Yulin, Shi Shulong, Jiang Shulong
Clinical Medical Laboratory Center, Jining First People's Hospital, Jining, 272000, China.
Department of Interventional Radiology, Jining First People's Hospital, Jining, 272000, China.
J Ethnopharmacol. 2025 Apr 25;346:119707. doi: 10.1016/j.jep.2025.119707. Epub 2025 Mar 26.
Euphorbia fischeriana Steud. (E. fischeriana) root is a well-known traditional Chinese medicine used in the treatment of skin ulceration, lymph node tuberculosis and tumors. However, its antitumor activity against HCC and the underlying molecular mechanisms remain to be further elucidated.
The study aimed to investigate the anti-hepatocarcinogenic effects of E. fischeriana root, specifically its impact on NCOA4-mediated ferritinophagy, and to elucidate the related molecular mechanisms in HCC.
LC-MS was used to analyze the comprehensive chemical composition of E. fischeriana root extract. Through network pharmacology, transcriptomics, molecular docking, and molecular dynamics simulations, we investigated the potential mechanisms underlying the effects of E. fischeriana root extract on HCC. Finally, in vitro and in vivo experiments were performed to validate these mechanisms.
Through mass spectrometry analysis and drug-likeness screening, 93 active compounds were identified. Based on network pharmacology and transcriptomic analyses, we hypothesized that the PI3K/AKT pathway and its downstream signaling involving autophagy and ferroptosis are crucial pathways affected by E. fischeriana root extract. In vitro experiments demonstrated that E. fischeriana root extract inhibits proliferation, promotes apoptosis, triggers ferritinophagy and induces ferroptosis in HCC cells. In vivo studies further validated significant anti-HCC effects of E. fischeriana root extract.
Based on these findings, we propose that E. fischeriana root extract exerts its anti-HCC effects by targeting the PI3K/AKT pathway to regulate NCOA4-mediated ferritinophagy, thereby inducing ferroptosis. These results highlight E. fischeriana root extract as a promising therapeutic candidate for HCC.
狼毒大戟根是一种著名的传统中药，用于治疗皮肤溃疡、淋巴结结核和肿瘤。然而，其对肝癌的抗肿瘤活性及潜在分子机制仍有待进一步阐明。
本研究旨在探讨狼毒大戟根的抗肝癌作用，特别是其对NCOA4介导的铁蛋白自噬的影响，并阐明肝癌中的相关分子机制。
采用液相色谱-质谱联用技术分析狼毒大戟根提取物的综合化学成分。通过网络药理学、转录组学、分子对接和分子动力学模拟，我们研究了狼毒大戟根提取物对肝癌作用的潜在机制。最后，进行体外和体内实验验证这些机制。
通过质谱分析和类药性筛选，鉴定出93种活性化合物。基于网络药理学和转录组分析，我们推测PI3K/AKT通路及其涉及自噬和铁死亡的下游信号是狼毒大戟根提取物影响的关键通路。体外实验表明，狼毒大戟根提取物抑制肝癌细胞增殖、促进凋亡、触发铁蛋白自噬并诱导铁死亡。体内研究进一步验证了狼毒大戟根提取物显著的抗肝癌作用。
基于这些发现，我们提出狼毒大戟根提取物通过靶向PI3K/AKT通路调节NCOA4介导的铁蛋白自噬，从而诱导铁死亡，发挥其抗肝癌作用。这些结果突出了狼毒大戟根提取物作为一种有前景的肝癌治疗候选药物。
