Wang Yuhua, Kuang Shanshan, Li Ke, Chen Shuni, Yang Min, Deng Kaili, Li Min, Xie Shuwen, Chen Qing, Wen Jinjie, Zhou Chuying, Cheng Weidong, Huang Sha, Lv Zhiping
School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China.
Commun Biol. 2025 Jul 21;8(1):1081. doi: 10.1038/s42003-025-08421-0.
Liver fibrosis is pathological progression of chronic liver disease. Recent research has focused on the activation of hepatic stellate cells (HSCs), highlighting their potential as targets for mitigating fibrosis. While herbal medicines and natural active ingredients have shown promising anti-fibrotic effects in clinical treatments, the impact of Astragalin (Ag) remains unexplored. In this study, we established in vivo and in vitro studies, employing fluorescence probe staining, transmission electron microscopy, and various analytical techniques. The results demonstrated Ag operates within a wide range of safe therapeutic doses in zebrafish and effectively alleviates liver fibrosis. Further experiments demonstrated that Ag induced HSCs ferroptosis via this pathway, leading to iron overload and ultimately alleviating liver fibrosis. In general, this study demonstrated that Ag promotes HSCs ferroptosis through NCOA4-mediated ferritinophagy, clarifying its mechanism in treating liver fibrosis and positioning Ag as a promising candidate for future clinical interventions.
肝纤维化是慢性肝病的病理进展。最近的研究集中在肝星状细胞（HSCs）的激活上，突出了它们作为减轻纤维化靶点的潜力。虽然草药和天然活性成分在临床治疗中已显示出有前景的抗纤维化作用，但黄芪甲苷（Ag）的影响仍未得到探索。在本研究中，我们建立了体内和体外研究，采用荧光探针染色、透射电子显微镜和各种分析技术。结果表明，Ag在斑马鱼体内的安全治疗剂量范围内有效发挥作用，并能有效减轻肝纤维化。进一步的实验表明，Ag通过该途径诱导HSCs铁死亡，导致铁过载并最终减轻肝纤维化。总体而言，本研究表明Ag通过NCOA4介导的铁自噬促进HSCs铁死亡，阐明了其治疗肝纤维化的机制，并将Ag定位为未来临床干预的有前景候选药物。
