Research progress on the mechanisms of ferroptosis in traditional Chinese medicine treatment of ischemic stroke

doi:10.3877/cma.j.issn.1673-9248.2026.02.014

Abstract

Abstract:

Ferroptosis is a type of programmed cell death characterized by iron-dependent lipid peroxidation accumulation, playing a significant role in the development of ischemic stroke (IS) and cerebral ischemia-reperfusion injury. Traditional Chinese medicine can intervene in the ferroptosis process by regulating key mechanisms such as iron metabolism imbalance, abnormal lipid peroxidation accumulation, and the antioxidant defense system, thereby exerting neuroprotective effects. This article reviews the primary mechanisms of ferroptosis in IS and the research progress of traditional Chinese medicine interventions, aiming to provide new research insights for the prevention and treatment of IS.

Key words: Ferroptosis, Ischemic stroke, Active ingredients of traditional Chinese medicine, Traditional Chinese medicine compound, Signaling pathway

Jichen Ma, Shaosong Wang, Xuefei Wang, Xu Ji, Guilin Liu. Research progress on the mechanisms of ferroptosis in traditional Chinese medicine treatment of ischemic stroke[J]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), 2026, 20(02): 209-214.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhnxgbzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1673-9248.2026.02.014

https://zhnxgbzz.cma-cmc.com.cn/EN/Y2026/V20/I02/209

Figures/Tables 1

References 54

1	Wu S, Wu B, Liu M, et al. Stroke in China: advances and challenges in epidemiology, prevention, and management [J]. Lancet Neurol, 2019, 18(4): 394-405.
2	Campbell BCV, De Silva DA, Macleod MR, et al. Ischaemic stroke [J]. Nat Rev Dis Primers, 2019, 5(1): 70.
3	Barthels D, Das H. Current advances in ischemic stroke research and therapies [J]. Biochim Biophys Acta Mol Basis Dis, 2020, 1866(4): 165260.
4	Feigin VL, Brainin M, Norrving B. World Stroke Organization (WSO): global stroke fact sheet 2022 [J]. Int J Stroke, 2022, 17(1): 18-29.
5	Zhou Z, Xu N, Matei N, et al. Sodium butyrate attenuated neuronal apoptosis via GPR41/Gβγ/PI3K/Akt pathway after MCAO in rats [J]. J Cereb Blood Flow Metab, 2021, 41(2): 267-281.
6	Lou Y, Ma M, Jiang Y, et al. Ferroptosis: a new strategy for traditional Chinese medicine treatment of stroke [J]. Biomed Pharmacother, 2022, 156: 113806.
7	Belaidi AA, Bush AI. Iron neurochemistry in Alzheimer's disease and Parkinson's disease: targets for therapeutics [J]. J Neurochem, 2016, 139(Suppl 1): 179-197.
8	Millán M, Sobrino T, Castellanos M, et al. Increased body iron stores are associated with poor outcome after thrombolytic treatment in acute stroke [J]. Stroke, 2007, 38(1): 90-95.
9	Jiang T, Cheng H, Su J, et al. Gastrodin protects against glutamate-induced ferroptosis in HT-22 cells through Nrf2/HO-1 signaling pathway [J]. Toxicol In Vitro, 2020, 62: 104715.
10	Yang M, Li X, Li H, et al. Baicalein inhibits RLS3-induced ferroptosis in melanocytes [J]. Biochem Biophys Res Commun, 2021, 561: 65-72.
11	Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death [J]. Cell, 2012, 149(5): 1060-1072.
12	Wu J, Hua Y, Keep RF, et al. Iron and iron-handling proteins in the brain after intracerebral hemorrhage [J]. Stroke, 2003, 34(12): 2964-2969.
13	Jacobson MD, Raff MC. Programmed cell death and Bcl-2 protection in very low oxygen [J]. Nature, 1995, 374(6525): 814-816.
14	Capelletti MM, Manceau H, Puy H, et al. Ferroptosis in liver diseases: an overview [J]. Int J Mol Sci, 2020, 21(14): 4908.
15	Kagan VE, Mao G, Qu F, et al. Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis [J]. Nat Chem Biol, 2017, 13(1): 81-90.
16	Doll S, Proneth B, Tyurina YY, et al. ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition [J]. Nat Chem Biol, 2017, 13(1): 91-98.
17	Hadian K, Stockwell BR. SnapShot: ferroptosis [J]. Cell, 2020, 181(5): 1188-1188.e1.
18	周文博, 孔晨飞, 秦高伟, 等. 铁死亡发生机制的研究进展 [J]. 生物化学与生物物理进展, 2018, 45(1): 16-22.
19	Cui Y, Zhang Y, Zhao X, et al. ACSL4 exacerbates ischemic stroke by promoting ferroptosis-induced brain injury and neuroinflammation [J]. Brain Behav Immun, 2021, 93: 312-321.
20	Zhang B, Zhang HX, Shi ST, et al. Interleukin-11 treatment protected against cerebral ischemia/reperfusion injury [J]. Biomed Pharmacother, 2019, 115: 108816.
21	Ali A, Shah FA, Zeb A, et al. NF-κB inhibitors attenuate MCAO induced neurodegeneration and oxidative stress [J]. Front Mol Neurosci, 2020, 13: 33.
22	Kuo PC, Weng WT, Scofield BA, et al. Interferon-β alleviates delayed tPA-induced adverse effects via modulation of MMP3/9 production in ischemic stroke [J]. Blood Adv, 2020, 4(18): 4366-4381.
23	Yi D, Wang Q, Zhao Y, et al. Alteration of N⁶-methyladenosine mRNA methylation in a rat model of cerebral ischemia-reperfusion injury [J]. Front Neurosci, 2021, 15: 605654.
24	Ding H, Yan CZ, Shi H, et al. Hepcidin is involved in iron regulation in the ischemic brain [J]. PLoS One, 2011, 6(9): e25324.
25	Freret T, Valable S, Chazalviel L, et al. Delayed administration of deferoxamine reduces brain damage after transient focal cerebral ischemia in rats [J]. Eur J Neurosci, 2006, 23(7): 1757-1765.
26	García-Yébenes I, Sobrado M, Moraga A, et al. Iron overload increases brain damage induced by focal ischemia and early reperfusion [J]. Neurochem Int, 2012, 61(8): 1364-1369.
27	Ahmad S, Elsherbiny NM, Haque R, et al. Sesamin attenuates neurotoxicity in mouse model of ischemic brain stroke [J]. Neurotoxicology, 2014, 45: 100-110.
28	Li C, Sun G, Chen B, et al. Nuclear receptor coactivator 4-mediated ferritinophagy contributes to cerebral ischemia-induced ferroptosis in ischemic stroke [J]. Pharmacol Res, 2021, 174: 105933.
29	张艾嘉, 王爽, 王萍, 等. 缺血性脑卒中的病理机制研究进展及中医药防治 [J]. 中国实验方剂学杂志, 2020, 26(5): 227-240.
30	Guan X, Li X, Yang X, et al. The neuroprotective effects of carvacrol on ischemia/reperfusion-induced hippocampal neuronal impairment by ferroptosis mitigation [J]. Life Sci, 2019, 235: 116795.
31	贾小慧, 王泽宇, 田嘉莹, 等. 丹参酮ⅡA通过抑制细胞色素P450 1B1/长链酰基辅酶A合成酶4通路介导铁死亡缓解缺血性脑卒中 [J]. 陕西医学杂志, 2025, 54(7): 882-887, 913.
32	李赛菲, 袁培培, 魏亚新, 等. 熟地黄通过抑制自噬和铁死亡改善缺血性脑卒中大鼠神经功能损伤 [J]. 中国实验方剂学杂志, 2024, 30(8): 26-33.
33	胡凯超, 高岩, 何佳琦, 等. 人参皂苷Rg1通过激活Nrf2/xCT/GPX4通路抑制神经元铁死亡改善缺血性脑卒中损伤 [J]. 中国药理学通报, 2023, 39(10): 1905-1913.
34	吴春阳, 欧阳竞锋. 姜黄素调控铁死亡干预帕金森病的网络药理学研究及实验验证 [J]. 海南医科大学学报, 2025, 31(5): 360-372.
35	Guo C, Tong L, Xi M, et al. Neuroprotective effect of calycosin on cerebral ischemia and reperfusion injury in rats [J]. J Ethnopharmacol, 2012, 144(3): 768-774.
36	Liu H, Zhao Z, Yan M, et al. Calycosin decreases cerebral ischemia/reperfusion injury by suppressing ACSL4-dependent ferroptosis [J]. Arch Biochem Biophys, 2023, 734: 109488.
37	Guan X, Li Z, Zhu S, et al. Galangin attenuated cerebral ischemia-reperfusion injury by inhibition of ferroptosis through activating the SLC7A11/GPX4 axis in gerbils [J]. Life Sci, 2021, 264: 118660.
38	刘敏, 肖颖, 左爱仁, 等. 槲皮素、根皮素、水飞蓟宾清除自由基和抑制脂质过氧化活性研究 [J]. 中成药, 2012, 34(4): 753-756.
39	杨迎暴, 朴英杰. 白藜芦醇对急性脊髓损伤早期脂质过氧化反应和活性氧水平的抑制作用 [J]. 中国临床药理学与治疗学, 2002, 7(3): 193-196.
40	Li X, Shang N, Kang Y, et al. Caffeic acid alleviates cerebral ischemic injury in rats by resisting ferroptosis via Nrf2 signaling pathway [J]. Acta Pharmacol Sin, 2024, 45(2): 248-267.
41	商廿颍, 李鑫楠, 刘梦瑶, 等. 咖啡酸对于脑缺血损伤的保护作用及机制 [J]. 中国药理学与毒理学杂志, 2023, 37(7): 518.
42	李含雪, 任秋月, 张嘉敏, 等. 葛根素多靶向抗氧化机制及其疾病干预策略 [J]. 中草药, 2026, 57(5): 1924-1937.
43	崔丹丹, 张小强. 原花青素通过Nrf2抑制Erastin介导的细胞铁死亡 [J]. 营养学报, 2024, 46(1): 40-47, 55.
44	张修红, 傅开龙, 林侃, 等. 补阳还五汤通过miR-26a-5p激活PTEN/PI3K/Akt信号通路减轻大鼠脑缺血再灌注损伤 [J]. 中国中药杂志, 2024, 49(15): 4197-4206.
45	张维轩, 郑洁, 柏鲁宁. 通窍活血汤对脑缺血大鼠铁死亡与炎症反应的影响 [J]. 中西医结合心脑血管病杂志, 2026, 24(3): 371-375.
46	何信用, 王俊岩, 宋囡, 等. 二陈汤合桃红四物汤调控p53/SLC7A11介导的氧化损伤及铁死亡抗动脉粥样硬化的作用及机制研究 [J]. 中华中医药杂志, 2020, 35(5): 2344-2348.
47	王文凤, 廖君, 张秀丽, 等. 脑泰方通过Nrf2调控抑制神经元铁死亡与焦亡减轻脑缺血再灌注损伤 [J]. 中国中药杂志, 2026, 51(2): 553-564.
48	贺超, 廖君, 兰斌, 等. 脑泰方对脑梗死后铁死亡-脂质代谢通路蛋白表达的影响 [J]. 中华中医药杂志, 2020, 35(11): 5491-5494.
49	向军军, 李丽琴, 李建铮, 等. 基于铁死亡探讨温阳复元方对脑缺血再灌注损伤大鼠神经损伤的保护机制 [J]. 中药新药与临床药理, 2023, 34(12): 1649-1657.
50	宋振海, 高峰. 胞磷胆碱联合醒脑静对高血压脑出血患者氧化应激、炎症反应以及神经功能的影响观察 [J]. 现代诊断与治疗, 2023, 34(14): 2124-2126.
51	黄贵金凤, 尚津锋, 文胤琏, 等. 脑心通胶囊通过铁死亡机制减轻大鼠脑缺血再灌注损伤研究 [J]. 中草药, 2025, 56(4): 1224-1233.
52	崔一然, 尚津锋, 焦家康, 等. 活血化瘀中药通过抑制铁死亡对MCAO大鼠脑缺血损伤的保护作用机制 [J]. 中华中医药杂志, 2023, 38(7): 3080-3085.
53	Ge Q, Wang Z, Yu J, et al. Chuanxiong Rhizoma regulates ferroptosis and the immune microenvironment in ischemic stroke through the JAK-STAT3 pathway [J]. Sci Rep, 2024, 14(1): 31224.
54	许卢春, 唐向盛, 俞兴, 等. 基于GPX4-ACSL4轴探讨补阳还五汤抑制铁死亡促进脊髓损伤后神经功能恢复的作用机制 [J]. 中国实验方剂学杂志, 2025, 31(5): 20-30.

[1]	Juanmin Zhang, Hai Wang, Yina Cao, Xin Zeng, Xiangjun Zha, Ying Liu, Hong Zhou, Yang Zhou. A responsive nanoplatform enabling high-intensity focused ultrasound-synergized ferroptosis and immunotherapy for triple-negative breast cancer [J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2026, 23(01): 67-76.
[2]	Chi Zhang, Yuhao Dong, Senming Cao, Chuang Wang, Yan Huang, Xu Zhang. APR-246 induces ferroptosis and cell cycle arrest in bladder cancer cells through reactivation of mutant p53 [J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2026, 16(01): 1-12.
[3]	Tiexin Liu, Zhenxia Wang. Research progress in cancer-associated fibroblasts in pancreatic ductal adenocarcinoma [J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2026, 15(01): 124-131.
[4]	Chenlong Liu, Yilei Xiao, Xiaohui Xing, Xueyuan Li. Research progress of miRNAs in modulating inflammatory responses via the NF-κB pathway to implicate for spinal cord injury prognosis [J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2026, 12(01): 52-56.
[5]	Liang Wang, Xiao Qu, Ping Lu, Lan Jiang, Qiong Liu, Jian Zou, Bin He. Research on PRDM5 in Crohn's disease through the Wnt/β-Catenin signaling pathway [J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2026, 16(02): 137-145.
[6]	Yi Zhou, Ronghua Huang, Zhengjiang Liu. Research progress of 5-hydroxytryptamine and ferroptosis-mediated septic cardiomyopathy [J]. Chinese Journal of Clinicians(Electronic Edition), 2025, 19(08): 612-617.
[7]	Yufeng Jiang, Rui Zhang, Hongwei Min. Heterotopic ossification following total joint arthroplasty: A review [J]. Chinese Journal of Clinicians(Electronic Edition), 2025, 19(07): 526-531.
[8]	Hailan Chen, Lizhou Wang. Mitophagy in cerebral ischemia-reperfusion injury: mechanisms and therapeutic implications [J]. Chinese Journal of Interventional Radiology(Electronic Edition), 2026, 14(01): 103-108.
[9]	Fenghua Xu, Tong Lu, Lian lian Zhu, Huan Wang, Lizhi Bai, Yi Song, Libin Zhan, Xiaoguang Lu. Mechanism of Dahuang Fuzi decoction inhibiting ferroptosis induced by hypoxia and reoxygenation in Caco-2 cells via SLC7A11/GPX4 pathway [J]. Chinese Journal of Hygiene Rescue(Electronic Edition), 2025, 11(06): 380-387.
[10]	Ziheng Shan, Fan Wang, Li Ma, Tao Zhang, Li Shao. Efficacy of head and neck CT angiography combined with head CT perfusion imaging for assessing short-term prognosis in patients with acute ischemic stroke [J]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), 2026, 20(02): 164-169.
[11]	Junyan Huo, Cuiting Zhu, Mingyue He, Xiuzhao Hu, Yun Wang. Analysis of factors influencing nutritional risk on admission in patients with acute ischemic stroke [J]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), 2026, 20(02): 170-177.
[12]	Hongrui Wang, Qian Jiang, Changqing Mu, Xiang Li, Xiaokun Geng, Fengwu Li. Dynamin-related protein 1-mediated mitochondrial fission regulates PANoptosis in ischemic neurons [J]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), 2026, 20(02): 185-196.
[13]	Zheng Long, Yi Ren, Peipei Li, Xiaoran Wang, He Bian, Yang Zhang, Yingmei Deng, Bingxin Ji, Qingfeng Ma. Analysis of the influencing factors of the length of stay for ischemic stroke patients based on data from the first page of medical records [J]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), 2026, 20(01): 16-24.
[14]	Wenguang Lin, Xinyi Liu, Lingfeng Wu. Research advances in diagnosis and treatment of progressive ischemic stroke [J]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), 2026, 20(01): 77-81.
[15]	Qiuhui Huang, Xuhui Deng, Hua Huang, Zhijian Liang. Research progress of endovascular thrombectomy in acute ischemic stroke patients beyond 24 hours [J]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), 2026, 20(01): 96-100.

Please choose a citation manager

Content to export