Research progress on mechanism of traditional Chinese medicine in treating Parkinson disease by interfering with ferroptosis

doi:10.16138/j.1673-6087.2024.05.13

Abstract

Abstract:

Ferroptosis is a newly recognized form of programmed cell death in recent years, and its core mechanism mainly involves the accumulation of iron-dependent lipid peroxides in cells. More and more studies suggest that ferroptosis plays a critical role in the onset and progression of Parkinson disease (PD). This article aims to review the molecular regulatory mechanism of ferroptosis in detail and the latest research progress on ferroptosis in treatment of PD and the therapeutic methods of traditional Chinese medicine for it. Through in-depth discussion of this emerging research field, the current status and progress of active ingredients and compounds of traditional Chinese medicine intervening process of PD through ferroptosis pathway were summarized, which was expected to provide a solid theoretical basis and innovative ideas for the application of targeting ferroptosis in the PD treatment.

Key words: Ferroptosis, Parkinson disease, Lipid peroxidation, Iron metabolism, Alpha-synuclein

CLC Number:

R742

LI Yuanyuan, YAO Xiaoling, QU Yanjie, CHEN Jingxian. Research progress on mechanism of traditional Chinese medicine in treating Parkinson disease by interfering with ferroptosis[J]. Journal of Internal Medicine Concepts & Practice, 2024, 19(05): 351-356.

References 48

[1]	Tolosa E, Garrido A, Scholz SW, et al. Challenges in the diagnosis of Parkinson’s disease[J]. Lancet Neurol, 2021, 20(5):385-397.
[2]	Tan C, Liu X, Chen J. Microarray analysis of the molecular mechanism involved in Parkinson’s disease[J]. Parkinsons Dis, 2018, 2018:1590465.
[3]	Xia J, Si H, Yao W, et al. Research progress on the mechanism of ferroptosis and its clinical application[J]. Exp Cell Res, 2021, 409(2):112932.
[4]	Dong-Chen X, Yong C, Yang X, et al. Signaling pathways in Parkinson’s disease: molecular mechanisms and therapeutic interventions[J]. Signal Transduct Target Ther, 2023, 8(1):73.
[5]	Ward RJ, Zucca FA, Duyn JH, et al. The role of iron in brain ageing and neurodegenerative disorders[J]. Lancet Neurol, 2014, 13(10):1045-1060. doi: 10.1016/S1474-4422(14)70117-6 pmid: 25231526
[6]	Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death[J]. Cell, 2012, 149(5):1060-1072. doi: 10.1016/j.cell.2012.03.042 pmid: 22632970
[7]	Chen H, Chen L, Wang W. Mechanisms and active substances of targeting lipid peroxidation in ferroptosis regulation[J]. Food Science and Human Wellness, 2024, 13(5):2502-2518.
[8]	Conrad M, Angeli JP, Vandenabeele P, et al. Regulated necrosis: disease relevance and therapeutic opportunities[J]. Nat Rev Drug Discov, 2016, 15(5):348-366. doi: 10.1038/nrd.2015.6 pmid: 26775689
[9]	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. doi: 10.1038/nchembio.2238 pmid: 27842066
[10]	Pietrangelo A. Hereditary hemochromatosis: pathogenesis, diagnosis, and treatment[J]. Gastroenterology, 2010, 139(2):393-408. doi: 10.1053/j.gastro.2010.06.013 pmid: 20542038
[11]	Plays M, Müller S, Rodriguez R. Chemistry and biology of ferritin[J]. Metallomics, 2021, 13(5):mfab021.
[12]	Hentze MW, Muckenthaler MU, Galy B, et al. Two to tango: regulation of Mammalian iron metabolism[J]. Cell, 2010, 142(1):24-38. doi: 10.1016/j.cell.2010.06.028 pmid: 20603012
[13]	Donovan A, Lima CA, Pinkus JL, et al. The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis[J]. Cell Metab, 2005, 1(3):191-200. doi: 10.1016/j.cmet.2005.01.003 pmid: 16054062
[14]	Kell DB. Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases[J]. BMC Med Genomics, 2009, 2:2. doi: 10.1186/1755-8794-2-2 pmid: 19133145
[15]	Sharon R, Bar-Joseph I, Frosch MP, et al. The formation of highly soluble oligomers of alpha-synuclein is regulated by fatty acids and enhanced in Parkinson’s disease[J]. Neuron, 2003, 37(4):583-595. doi: 10.1016/s0896-6273(03)00024-2 pmid: 12597857
[16]	Burré J, Sharma M, Tsetsenis T, et al. Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro[J]. Science, 2010, 329(5999):1663-1667.
[17]	Angelova PR, Choi ML, Berezhnov AV, et al. Alpha synuclein aggregation drives ferroptosis: an interplay of iron, calcium and lipid peroxidation[J]. Cell Death Differ, 2020, 27(9):2747. doi: 10.1038/s41418-020-0552-x pmid: 32409771
[18]	Baksi S, Tripathi AK, Singh N. Alpha-synuclein modulates retinal iron homeostasis by facilitating the uptake of transferrin-bound iron: implications for visual manifestations of Parkinson’s disease[J]. Free Radic Biol Med, 2016, 97:292-306.
[19]	Bi M, Du X, Jiao Q, et al. α-synuclein regulates iron homeostasis via preventing parkin-mediated DMT1 ubiquitylation in Parkinson’s disease models[J]. ACS Chem Neurosci, 2020, 11(11):1682-1691.
[20]	Do Van B, Gouel F, Jonneaux A, et al. Ferroptosis, a newly characterized form of cell death in Parkinson’s disease that is regulated by PKC[J]. Neurobiol Dis, 2016, 94:169-178.
[21]	Zecca L, Wilms H, Geick S, et al. Human neuromelanin induces neuroinflammation and neurodegeneration in the rat substantia nigra: implications for Parkinson’s disease[J]. Acta Neuropathol, 2008, 116(1):47-55.
[22]	Mahoney-Sánchez L, Bouchaoui H, Ayton S, et al. Ferroptosis and its potential role in the physiopathology of Parkinson’s Disease[J]. Prog Neurobiol, 2021, 196:101890.
[23]	Zheng K, Dong Y, Yang R, et al. Regulation of ferroptosis by bioactive phytochemicals: implications for medical nutritional therapy[J]. Pharmacol Res, 2021, 168:105580.
[24]	Lou JS, Zhao LP, Huang ZH, et al. Ginkgetin derived from Ginkgo biloba leaves enhances the therapeutic effect of cisplatin via ferroptosis-mediated disruption of the Nrf2/HO-1 axis in EGFR wild-type non-small-cell lung cancer[J]. Phytomedicine, 2021, 80:153370.
[25]	Kong N, Chen X, Feng J, et al. Baicalin induces ferroptosis in bladder cancer cells by downregulating FTH1[J]. Acta Pharm Sin B, 2021, 11(12):4045-4054.
[26]	李毛, 杨东东, 徐江雁. 莫诺苷药理作用研究进展[J]. 中华中医药学刊, 2023, 41(10):70-75.
[27]	Li M, Zhang J, Jiang L, et al. Neuroprotective effects of morroniside from Cornus officinalis sieb. Et zucc against Parkinson’s disease via inhibiting oxidative stress and ferroptosis[J]. BMC Complement Med Ther, 2023, 23(1):218.
[28]	Zhang L, Deng M, Wang SY, et al. Mitigation of paeoniae radix alba extracts on H2O2-induced oxidative damage in HepG2 cells and hyperglycemia in zebrafish, and identification of phytochemical constituents[J]. Front Nutr, 2023, 10:1135759.
[29]	贾岚, 王蕾蕾, 孟靓, 等. 白芍对酒精性肝损伤肝阴虚证的保护功效和机制[J]. 北京中医药大学学报, 2020, 43(3):203-211.
[30]	Wang L, An H, Yu F, et al. The neuroprotective effects of paeoniflorin against MPP⁺-induced damage to dopaminergic neurons via the Akt/Nrf2/GPX4 pathway[J]. J Chem Neuroanat, 2022, 122:102103.
[31]	Guo K, Zhang Y, Li L, et al. Neuroprotective effect of paeoniflorin in the mouse model of Parkinson’s disease through α-synuclein/protein kinase C δ subtype signaling pathway[J]. Neuroreport, 2021, 32(17):1379-1387.
[32]	Liu L, Yang S, Wang H. α-Lipoic acid alleviates ferroptosis in the MPP⁺ -induced PC12 cells via activating the PI3K/Akt/Nrf2 pathway[J]. Cell Biol Int, 2021, 45(2):422-431.
[33]	Abo Laban AI, El-Bassossy HM, Hassan NA. Hinokitiol produces vasodilation in aortae from normal and angiotensin Ⅱ- induced hypertensive rats via endothelial-dependent and independent pathways[J]. Vascul Pharmacol, 2022, 146:107092.
[34]	Jin X, Zhang M, Lu J, et al. Hinokitiol chelates intracellular iron to retard fungal growth by disturbing mitochondrial respiration[J]. J Adv Res, 2021, 34:65-77. doi: 10.1016/j.jare.2021.06.016 pmid: 35024181
[35]	Che Z, Liu Y, Chen L, et al. Synthesis of hinokitiol sulfonate derivatives and their anti-oomycete and nematicidal activities[J]. Chem Biodivers, 2022, 19(9):e202200580.
[36]	Qiao Y, Zhang M, Cao Y, et al. Postharvest sclerotinia rot control in carrot by the natural product hinokitiol and the potential mechanisms involved[J]. Int J Food Microbiol, 2022, 383:109939.
[37]	Xi J, Zhang Z, Wang Z, et al. Hinokitiol functions as a ferroptosis inhibitor to confer neuroprotection[J]. Free Radic Biol Med, 2022, 190:202-215.
[38]	Jiang Y, Xie G, Alimujiang A, et al. Protective effects of querectin against MPP+-induced dopaminergic neurons injury via the Nrf2 signaling pathway[J]. Front Biosci (Landmark Ed), 2023, 28(3):42.
[39]	刘佳, 朱柏雨, 杨星, 等. 赶黄草活性成分及主要功效作用研究进展[J]. 四川农业科技, 2024(2):137-140.
[40]	Sun Y, He L, Wang W, et al. Activation of Atg7-dependent autophagy by a novel inhibitor of the Keap1-Nrf2 protein-protein interaction from Penthorum chinense Pursh. attenuates 6-hydroxydopamine-induced ferroptosis in zebrafish and dopaminergic neurons[J]. Food Funct, 2022, 13(14):7885-7900.
[41]	梁子红, 谢鹏, 朱润秀, 等. 银杏叶提取物对神经系统疾病作用的研究进展[J]. 中国实用神经疾病杂志, 2018, 21(5):570-575.
[42]	张辉, 马惠清, 王晓娟. 银杏叶提取物通过激活Nrf2-ARE信号通路对帕金森病大鼠发挥脑保护作用[J]. 沈阳药科大学报, 2018, 35(8):675-679+695.
[43]	Yang K, Zeng L, Zeng J, et al. Research progress in the molecular mechanism of ferroptosis in Parkinson’s disease and regulation by natural plant products[J]. Ageing Res Rev, 2023, 91:102063.
[44]	Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death[J]. Cell, 2012, 149(5):1060-1072. doi: 10.1016/j.cell.2012.03.042 pmid: 22632970
[45]	Bartzokis G, Cummings JL, Markham CH, et al. MRI evaluation of brain iron in earlier- and later-onset Parkinson’s disease and normal subjects[J]. Magn Reson Imaging, 1999, 17(2):213-222. doi: 10.1016/s0730-725x(98)00155-6 pmid: 10215476
[46]	Lewis MM, Du G, Baccon J, et al. Susceptibility MRI captures nigral pathology in patients with parkinsonian syndromes[J]. Mov Disord, 2018, 33(9):1432-1439.
[47]	郭宇婷. 天麻钩藤饮调控ACSL4介导的脂质过氧化抑制细胞铁死亡延缓PD进程的初步研究[D]. 安徽中医药大学, 2022.
[48]	李晨, 王鹏, 王亮, 等. 补肾活血颗粒对亚急性帕金森病模型小鼠脑黑质多巴胺神经元铁死亡的影响[J]. 中医杂志, 2022, 63(15):1463-1469.