Alum Esther Ugo, Akwari Ada Ak, Okoroh Prince Nkemakolam, Aniokete Ugonna Cassandra, Abba Jacinta Nnennaya, Uti Daniel Ejim
Department of Research and Publications, Kampala International University, P. O. Box 20000, Kampala, Uganda.
Department of Biochemsitry, Faculty of Science, Ebonyi State University, Abakaliki, Nigeria.
Mol Biol Rep. 2025 Jun 25;52(1):636. doi: 10.1007/s11033-025-10752-4.
Ferroptosis, a controlled cell death mechanism characterised by iron-dependent lipid peroxidation, has become a significant factor in the pathophysiology of cancer and neurodegenerative disorders. Its dual role as a tumor suppressor and mediator of neuronal damage highlights its significance as a therapeutic target. Phytochemicals, natural bioactive molecules in plants, have attracted interest for their ability to modulate ferroptosis through diverse mechanisms, including regulation of oxidative stress, iron metabolism, and antioxidant defense systems. This review examines the complex relationship between ferroptosis and disease mechanisms, emphasizing its relevance in treatment-resistant cancers and neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Information was taken from reputable databases such as PubMed, Scopus, and Web of Science. We thoroughly analyzed the current evidence on phytochemicals-including polyphenols like curcumin and epigallocatechin gallate, flavonoids like quercetin and luteolin, and alkaloids like berberine-as modulators of ferroptotic pathways. Despite their promising therapeutic potential, challenges such as limited bioavailability, pharmacokinetics, and clinical validation remain significant hurdles. Future research focusing on advanced delivery systems, synergistic approaches, and personalized medicine strategies could unlock the full potential of phytochemicals in ferroptosis-targeted therapies. This review underscores phytochemicals as a novel and versatile avenue in addressing the unmet therapeutic needs in cancer and neurodegenerative diseases.
铁死亡是一种由铁依赖性脂质过氧化作用所表征的可控细胞死亡机制,已成为癌症和神经退行性疾病病理生理学中的一个重要因素。其作为肿瘤抑制因子和神经元损伤介质的双重作用凸显了其作为治疗靶点的重要性。植物化学物质是植物中的天然生物活性分子,因其能够通过多种机制调节铁死亡而受到关注,这些机制包括对氧化应激、铁代谢和抗氧化防御系统的调节。本综述探讨了铁死亡与疾病机制之间的复杂关系,强调了其在难治性癌症以及阿尔茨海默病和帕金森病等神经退行性疾病中的相关性。信息来源于PubMed、Scopus和Web of Science等知名数据库。我们全面分析了目前关于植物化学物质的证据,这些植物化学物质包括姜黄素和表没食子儿茶素没食子酸酯等多酚类、槲皮素和木犀草素等黄酮类以及小檗碱等生物碱类,它们作为铁死亡途径的调节剂。尽管它们具有潜在的治疗潜力,但生物利用度有限、药代动力学和临床验证等挑战仍然是重大障碍。未来聚焦于先进递送系统、协同方法和个性化医疗策略的研究可能会释放植物化学物质在铁死亡靶向治疗中的全部潜力。本综述强调植物化学物质是满足癌症和神经退行性疾病未满足治疗需求的一条新颖且通用的途径。