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2000
Volume 31, Issue 25
  • ISSN: 1381-6128
  • E-ISSN: 1873-4286

Abstract

Parkinson's Disease (PD) is a neurodegenerative disorder of the central nervous system (CNS). Given the increasing age of the general population, PD has emerged as a significant public health and societal concern, impacting both individual well-being and socioeconomic progress. The present interventions have proven insufficient in impeding the progressive nature of PD. Consequently, it is imperative to promptly identify efficacious strategies for the prevention and treatment of PD. Icaritin (ICT) is a flavonoid extracted from Epimedium Brevicornu Maxim that is a phytoestrogen with antitumour, anti-inflammatory, antioxidant, antiaging, and neuroprotective properties. This paper reviews the protective effect of ICT on dopaminergic neurons through anti-oxidative stress, improving mitochondrial function, inhibiting neuroinflammatory responses, reducing Lewy body formation, and decreasing apoptosis. The primary objective of this article is to provide valuable insights and serve as a reference for the potential use of ICT in the prevention and treatment of PD.

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2025-02-10
2025-10-22
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References

  1. Ben-ShlomoY. DarweeshS. Llibre-GuerraJ. MarrasC. San LucianoM. TannerC. The epidemiology of Parkinson’s disease.Lancet20244031042328329210.1016/S0140‑6736(23)01419‑838245248
    [Google Scholar]
  2. MorrisH.R. SpillantiniM.G. SueC.M. Williams-GrayC.H. The pathogenesis of Parkinson’s disease.Lancet20244031042329330410.1016/S0140‑6736(23)01478‑238245249
    [Google Scholar]
  3. LvQ.K. TaoK.X. WangX.B. YaoX.Y. PangM.Z. LiuJ.Y. WangF. LiuC.F. Role of α-synuclein in microglia: Autophagy and phagocytosis balance neuroinflammation in Parkinson’s disease.Inflamm. Res.202372344346210.1007/s00011‑022‑01676‑x36598534
    [Google Scholar]
  4. ZhangW.D. LiN. DuZ.R. ZhangM. ChenS. ChenW.F. IGF-1 receptor is involved in the regulatory effects of icariin and icaritin in astrocytes under basal conditions and after an inflammatory challenge.Eur. J. Pharmacol.202190617426910.1016/j.ejphar.2021.17426934147477
    [Google Scholar]
  5. ZhangH. WangH. WeiJ. ChenX. SunM. OuyangH. HaoJ. ChangY. DouZ. HeJ. Comparison of the active compositions between raw and processed Epimedium from different species.Molecules2018237165610.3390/molecules2307165629986486
    [Google Scholar]
  6. LiuF.Y. DingD.N. WangY.R. LiuS.X. PengC. ShenF. ZhuX.Y. LiC. TangL.P. HanF.J. Icariin as a potential anticancer agent: A review of its biological effects on various cancers.Front. Pharmacol.202314121636310.3389/fphar.2023.121636337456751
    [Google Scholar]
  7. MaY. ZhaoC. HuH. YinS. Liver protecting effects and molecular mechanisms of icariin and its metabolites.Phytochemistry202321511384110.1016/j.phytochem.2023.11384137660725
    [Google Scholar]
  8. JiangW. DingK. YueR. LeiM. Therapeutic effects of icariin and icariside II on diabetes mellitus and its complications.Crit. Rev. Food Sci. Nutr.2023641758527710.1080/10408398.2022.215931736591787
    [Google Scholar]
  9. ZhengL. WuS. JinH. WuJ. WangX. CaoY. ZhouZ. JiangY. LiL. YangX. ShenQ. GuoS. ShenY. LiC. JiL. Molecular mechanisms and therapeutic potential of icariin in the treatment of Alzheimer’s disease.Phytomedicine202311615489010.1016/j.phymed.2023.15489037229892
    [Google Scholar]
  10. WangY. ShangC. ZhangY. XinL. JiaoL. XiangM. ShenZ. ChenC. DingF. LuY. CuiX. Regulatory mechanism of icariin in cardiovascular and neurological diseases.Biomed. Pharmacother.202315811415610.1016/j.biopha.2022.11415636584431
    [Google Scholar]
  11. LiuS. LiuC.M. LaiL.J. LiL.D. Progress in the study of the pharmacological effects of Icaritin.J. Gannan Med. Uni.20173704631635
    [Google Scholar]
  12. XiaoQ. FanH.J. LiY.R. SunR.R. JiaL. XuL. WeiJ.Z. XiaoB.G. MaC.G. CaiZ. Advances in Parkinson’s disease pathogenesis.Med. J. Chinese People’s Liberation Army.20234808983992
    [Google Scholar]
  13. IsikS. KiyakBY AkbayirR. SeyhaliR. ArpaciT. Microglia mediated neuroinflammation in Parkinson’s disease.Cells2023127101210.3390/cells1207101237048085
    [Google Scholar]
  14. YuH. ChangQ. SunT. HeX. WenL. AnJ. FengJ. ZhaoY. Metabolic reprogramming and polarization of microglia in Parkinson’s disease: Role of inflammasome and iron.Ageing Res. Rev.20239010203210.1016/j.arr.2023.10203237572760
    [Google Scholar]
  15. PataniR. HardinghamG.E. LiddelowS.A. Functional roles of reactive astrocytes in neuroinflammation and neurodegeneration.Nat. Rev. Neurol.202319739540910.1038/s41582‑023‑00822‑137308616
    [Google Scholar]
  16. YangY. JiangG.Y. JinM.R. LiJ.J. LiuZ.M. ChenW.F. Neuronal damage caused by lipopolysaccharide-activated mesencephalon glial cell-conditioned medium and the neuroprotective effect of icaritin.J. Qingdao Uni. (Med. Sci.).20215702182185
    [Google Scholar]
  17. WuH. LiuX. GaoZ.Y. LinM. ZhaoX. SunY. PuX.P. Icaritin provides neuroprotection in Parkinson’s disease by attenuating neuroinflammation, oxidative stress, and energy deficiency.Antioxidants202110452910.3390/antiox1004052933805302
    [Google Scholar]
  18. HwangE. LinP. NgoH.T.T. GaoW. WangY.S. YuH.S. YiT.H. Icariin and icaritin recover UVB-induced photoaging by stimulating Nrf2/ARE and reducing AP-1 and NF-κB signaling pathways: A comparative study on UVB-irradiated human keratinocytes.Photochem. Photobiol. Sci.201817101396140810.1039/c8pp00174j30225503
    [Google Scholar]
  19. ArterburnJ.B. ProssnitzE.R. G protein–coupled estrogen receptor GPER: Molecular pharmacology and therapeutic applications.Annu. Rev. Pharmacol. Toxicol.202363129532010.1146/annurev‑pharmtox‑031122‑12194436662583
    [Google Scholar]
  20. ProssnitzE.R. BartonM. The G protein-coupled oestrogen receptor GPER in health and disease: An update.Nat. Rev. Endocrinol.202319740742410.1038/s41574‑023‑00822‑737193881
    [Google Scholar]
  21. FenderD. HarperW.M. GreggP.J. The trent regional arthroplasty study.J. Bone Joint Surg. Br.200082-B794494710.1302/0301‑620X.82B7.082094411041579
    [Google Scholar]
  22. YuT. YangG. HouY. TangX. WuC. WuX. GuoL. ZhuQ. LuoH. DuY. WenS. XuL. YinJ. TuG. LiuM. Cytoplasmic GPER translocation in cancer-associated fibroblasts mediates cAMP/PKA/CREB/glycolytic axis to confer tumor cells with multidrug resistance.Oncogene201736152131214510.1038/onc.2016.37027721408
    [Google Scholar]
  23. KilpatrickL.E. HillS.J. Transactivation of G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs): Recent insights using luminescence and fluorescence technologies.Curr. Opin. Endocr. Metab. Res.20211610211210.1016/j.coemr.2020.10.00333748531
    [Google Scholar]
  24. YuZ. SuG. ZhangL. LiuG. ZhouY. FangS. ZhangQ. WangT. HuangC. HuangZ. LiL. Icaritin inhibits neuroinflammation in a rat cerebral ischemia model by regulating microglial polarization through the GPER–ERK–NF-κB signaling pathway.Mol. Med.202228114210.1186/s10020‑022‑00573‑736447154
    [Google Scholar]
  25. YaoW. TaoR. WangK. DingX. Icariin attenuates vascular endothelial dysfunction by inhibiting inflammation through GPER/Sirt1/HMGB1 signaling pathway in type 1 diabetic rats.Chin. J. Nat. Med.202422429330610.1016/S1875‑5364(24)60618‑738658093
    [Google Scholar]
  26. Yang Y. Experimental study of the anti-inflammatory response to icariin and icaritin via GPER in Parkinson's disease. Qingdao University 2022.
  27. GuanJ. YangB. FanY. ZhangJ. GPER agonist G1 attenuates neuroinflammation and dopaminergic neurodegeneration in Parkinson disease.Neuroimmunomodulation2017241606610.1159/00047890828810246
    [Google Scholar]
  28. Mendes-OliveiraJ. CamposFL VideiraR.A. BaltazarG. GPER activation is effective in protecting against inflammation-induced nigral dopaminergic loss and motor function impairment.Brain Behav. Immun.20176429630710.1016/j.bbi.2017.04.01628450223
    [Google Scholar]
  29. JiangM.C. ChenX.H. ZhaoX. ZhangX.J. ChenW.F. Involvement of IGF-1 receptor signaling pathway in the neuroprotective effects of Icaritin against MPP(+)-induced toxicity in MES23.5 cells.Eur. J. Pharmacol.2016786535910.1016/j.ejphar.2016.05.03127238975
    [Google Scholar]
  30. MishraE. ThakurM.K. Mitophagy: A promising therapeutic target for neuroprotection during ageing and age-related diseases.Br. J. Pharmacol.2023180121542156110.1111/bph.1606236792062
    [Google Scholar]
  31. Von StockumS. NardinA. SchrepferE. ZivianiE. Mitochondrial dynamics and mitophagy in Parkinson’s disease: A fly point of view.Neurobiol. Dis.201690586710.1016/j.nbd.2015.11.00226550693
    [Google Scholar]
  32. BurtéF. CarelliV. ChinneryP.F. Yu-Wai-ManP. Disturbed mitochondrial dynamics and neurodegenerative disorders.Nat. Rev. Neurol.2015111112410.1038/nrneurol.2014.22825486875
    [Google Scholar]
  33. ElfawyH.A. DasB. Crosstalk between mitochondrial dysfunction, oxidative stress, and age related neurodegenerative disease: Etiologies and therapeutic strategies.Life Sci.201921816518410.1016/j.lfs.2018.12.02930578866
    [Google Scholar]
  34. OnyangoI.G. LuJ. RodovaM. LeziE. CrafterA.B. SwerdlowR.H. Regulation of neuron mitochondrial biogenesis and relevance to brain health.Biochim. Biophys. Acta Mol. Basis Dis.20101802122823410.1016/j.bbadis.2009.07.01419682571
    [Google Scholar]
  35. ChenY. ZhuG. YuanT. MaR. ZhangX. MengF. YangA. DuT. ZhangJ. Subthalamic nucleus deep brain stimulation alleviates oxidative stress via mitophagy in Parkinson’s disease.NPJ Parkinsons Dis.20241015210.1038/s41531‑024‑00668‑438448431
    [Google Scholar]
  36. JomovaK. RaptovaR. AlomarS.Y. AlwaselS.H. NepovimovaE. KucaK. ValkoM. Reactive oxygen species, toxicity, oxidative stress, and antioxidants: Chronic diseases and aging.Arch. Toxicol.202397102499257410.1007/s00204‑023‑03562‑937597078
    [Google Scholar]
  37. TeleanuD.M. NiculescuA.G. LunguI.I. RaduC.I. VladâcencoO. RozaE. CostăchescuB. GrumezescuA.M. TeleanuR.I. An overview of oxidative stress, neuroinflammation, and neurodegenerative diseases.Int. J. Mol. Sci.20222311593810.3390/ijms2311593835682615
    [Google Scholar]
  38. ParkJ.S. DavisR.L. SueC.M. Mitochondrial dysfunction in Parkinson’s disease: New mechanistic insights and therapeutic perspectives.Curr. Neurol. Neurosci. Rep.20181852110.1007/s11910‑018‑0829‑329616350
    [Google Scholar]
  39. Franco-IborraS. VilaM. PerierC. Mitochondrial quality control in neurodegenerative diseases: Focus on Parkinson’s disease and Huntington’s disease.Front. Neurosci.20181234210.3389/fnins.2018.0034229875626
    [Google Scholar]
  40. GangulyG. ChakrabartiS. ChatterjeeU. SasoL. Proteinopathy, oxidative stress and mitochondrial dysfunction: Cross talk in Alzheimer’s disease and Parkinson’s disease.Drug Des. Devel. Ther.20171179781010.2147/DDDT.S13051428352155
    [Google Scholar]
  41. KlemmensenM.M. BorrowmanS.H. PearceC. PylesB. ChandraB. Mitochondrial dysfunction in neurodegenerative disorders.Neurotherapeutics2024211e0029210.1016/j.neurot.2023.10.00238241161
    [Google Scholar]
  42. DuX. XieX. LiuR. The role of α-synuclein oligomers in Parkinson’s disease.Int. J. Mol. Sci.20202122864510.3390/ijms2122864533212758
    [Google Scholar]
  43. LiuC. DingX. GuoX. ZhaoM. ZhangX. LiZ. ZhaoR. CaoY. XingJ. Recombinant human HspB5-ACD structural domain inhibits neurotoxicity by regulating pathological α-Syn aggregation.Int. J. Biol. Macromol.202425512831110.1016/j.ijbiomac.2023.12831137992927
    [Google Scholar]
  44. SommerS.P. SommerS. SinhaB. WalterD. AleksicI. GohrbandtB. OttoC. LeyhR.G. Glutathione preconditioning ameliorates mitochondria dysfunction during warm pulmonary ischemia-reperfusion injury.Eur. J. Cardiothorac. Surg.201241114014821596579
    [Google Scholar]
  45. PiccaA. GuerraF. CalvaniR. RomanoR. Coelho-JúniorH.J. BucciC. MarzettiE. Mitochondrial dysfunction, protein misfolding and neuroinflammation in Parkinson’s disease: Roads to biomarker discovery.Biomolecules20211110150810.3390/biom1110150834680141
    [Google Scholar]
  46. ZhouX. HuangN. HouX. ZhuL. XieY. BaZ. LuoY. Icaritin attenuates 6-OHDA-induced MN9D cell damage by inhibiting oxidative stress.PeerJ202210e1325610.7717/peerj.1325635433120
    [Google Scholar]
  47. LiQ. HuaiL. ZhangC. WangC. JiaY. ChenY. YuP. WangH. RaoQ. WangM. WangJ. Icaritin induces AML cell apoptosis via the MAPK/ERK and PI3K/AKT signal pathways.Int. J. Hematol.201397561762310.1007/s12185‑013‑1317‑923550021
    [Google Scholar]
  48. LouY. ZouL. ShenZ. ZhengJ. LinY. ZhangZ. ChenX. PanJ. ZhangX. Protective effect of dexmedetomidine against delayed bone healing caused by morphine via PI3K/Akt mediated Nrf2 antioxidant defense system.Front. Pharmacol.202415139671310.3389/fphar.2024.139671338863982
    [Google Scholar]
  49. UlasovA.V. RosenkranzA.A. GeorgievG.P. SobolevA.S. Nrf2/Keap1/ARE signaling: Towards specific regulation.Life Sci.202229112011110.1016/j.lfs.2021.12011134732330
    [Google Scholar]
  50. ChenG.H. SongC.C. PantopoulosK. WeiX.L. ZhengH. LuoZ. Mitochondrial oxidative stress mediated Fe-induced ferroptosis via the NRF2-ARE pathway.Free Radic. Biol. Med.20221809510710.1016/j.freeradbiomed.2022.01.01235045311
    [Google Scholar]
  51. Dinkova-KostovaAT AbramovAY The emerging role of Nrf2 in mitochondrial function.Free Radic Biol Med201588Pt B17918810.1016/j.freeradbiomed.2015.04.03625975984
    [Google Scholar]
  52. VasconcelosA.R. dos SantosN.B. ScavoneC. MunhozC.D. Nrf2/ARE pathway modulation by dietary energy regulation in neurological disorders.Front. Pharmacol.2019103310.3389/fphar.2019.0003330778297
    [Google Scholar]
  53. ZhangB. WangG. HeJ. YangQ. LiD. LiJ. ZhangF. Icariin attenuates neuroinflammation and exerts dopamine neuroprotection via an Nrf2-dependent manner.J. Neuroinflammation20191619210.1186/s12974‑019‑1472‑x31010422
    [Google Scholar]
  54. WuJ. XuH. WongP.F. XiaS. XuJ. DongJ. Icaritin attenuates cigarette smoke-mediated oxidative stress in human lung epithelial cells via activation of PI3K-AKT and Nrf2 signaling.Food Chem. Toxicol.20146430731310.1016/j.fct.2013.12.00624333105
    [Google Scholar]
  55. Martínez-LimónA. JoaquinM. CaballeroM. PosasF. de NadalE. The p38 pathway: From biology to cancer therapy.Int. J. Mol. Sci.2020216191310.3390/ijms2106191332168915
    [Google Scholar]
  56. GravandiM.M. AbdianS. TahvilianM. IranpanahA. MoradiS.Z. FakhriS. EcheverríaJ. Therapeutic targeting of Ras/Raf/MAPK pathway by natural products: A systematic and mechanistic approach for neurodegeneration.Phytomedicine202311515482110.1016/j.phymed.2023.15482137119761
    [Google Scholar]
  57. PyakurelA. SavoiaC. HessD. ScorranoL. Extracellular regulated kinase phosphorylates mitofusin 1 to control mitochondrial morphology and apoptosis.Mol. Cell201558224425410.1016/j.molcel.2015.02.02125801171
    [Google Scholar]
  58. BohushA. NiewiadomskaG. FilipekA. Role of mitogen activated protein kinase signaling in Parkinson’s disease.Int. J. Mol. Sci.20181910297310.3390/ijms1910297330274251
    [Google Scholar]
  59. IbaM. KimC. KwonS. SzaboM. Horan-PortelanceL. PeerC.J. FiggW.D. ReedX. DingJ. LeeS.J. RissmanR.A. CooksonM.R. OverkC. WrasidloW. MasliahE. Inhibition of p38α MAPK restores neuronal p38γ MAPK and ameliorates synaptic degeneration in a mouse model of DLB/PD.Sci. Transl. Med.202315695eabq608910.1126/scitranslmed.abq608937163617
    [Google Scholar]
  60. MattsonM.P. Neuronal life-and-death signaling, apoptosis, and neurodegenerative disorders.Antioxid. Redox Signal.2006811-121997200610.1089/ars.2006.8.199717034345
    [Google Scholar]
  61. NovikovaL. GarrisB.L. GarrisD.R. LauY.S. Early signs of neuronal apoptosis in the substantia nigra pars compacta of the progressive neurodegenerative mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid model of Parkinson’s disease.Neuroscience20061401677610.1016/j.neuroscience.2006.02.00716533572
    [Google Scholar]
  62. GhavamiS. ShojaeiS. YeganehB. AndeS.R. JangamreddyJ.R. MehrpourM. ChristofferssonJ. ChaabaneW. MoghadamA.R. KashaniH.H. HashemiM. OwjiA.A. ŁosM.J. Autophagy and apoptosis dysfunction in neurodegenerative disorders.Prog. Neurobiol.2014112244910.1016/j.pneurobio.2013.10.00424211851
    [Google Scholar]
  63. FuchsY. StellerH. Programmed cell death in animal development and disease.Cell2011147474275810.1016/j.cell.2011.10.03322078876
    [Google Scholar]
  64. QiaoC. YeW. LiS. WangH. DingX. Icariin modulates mitochondrial function and apoptosis in high glucose-induced glomerular podocytes through G protein-coupled estrogen receptors.Mol. Cell. Endocrinol.201847314615510.1016/j.mce.2018.01.01429373840
    [Google Scholar]
  65. WangK. ZhengX. PanZ. YaoW. GaoX. WangX. DingX. Icariin prevents extracellular matrix accumulation and ameliorates experimental diabetic kidney disease by inhibiting oxidative stress via GPER mediated p62-dependent keap1 degradation and Nrf2 activation.Front. Cell Dev. Biol.2020855910.3389/fcell.2020.0055932766240
    [Google Scholar]
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