2. Academic Validation
  3. Mechanism and molecular targets of Euphorbia fischeriana Steud root extract in hepatocellular carcinoma

Mechanism and molecular targets of Euphorbia fischeriana Steud root extract in hepatocellular carcinoma

  • J Ethnopharmacol. 2025 Apr 25:346:119707. doi: 10.1016/j.jep.2025.119707.
Xinchen Tian 1,  Fen Liu 1,  Jing Zhao 1,  Qingbin Liu 1,  Haochen Wang 2,  Yanmei Liu 3,  Jiaqi Zhang 1,  Yiming Zhang 1,  Yulin Yang 4,  Shulong Shi 5,  Shulong Jiang 6
Affiliations

Affiliations

  • 1 Clinical Medical Laboratory Center, Jining First People's Hospital, Jining, 272000, China.
  • 2 Department of Interventional Radiology, Jining First People's Hospital, Jining, 272000, China.
  • 3 Department of Pathology, Jining Public Health Medical Center, Jining, 272000, China.
  • 4 Department of Pathology, Jining Public Health Medical Center, Jining, 272000, China. Electronic address: ykyyl@126.com.
  • 5 Department of Endocrinology, Jining First People's Hospital, Jining, 272000, China. Electronic address: 529306267@qq.com.
  • 6 Clinical Medical Laboratory Center, Jining First People's Hospital, Jining, 272000, China. Electronic address: jnsljiang@163.com.
PMID: 40147679 DOI: 10.1016/j.jep.2025.119707
Abstract

Ethnopharmacological relevance: 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.

Aim of the study: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords

Euphorbia fischeriana Steud. root extract; Ferritinophagy; Ferroptosis; Hepatocellular carcinoma.

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