Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Pharmaceutical Design
  4. Fast Track Articles
  5. Fast Track Article
image of Therapeutic Effects and Mechanisms of Icaritin in Parkinson's Disease

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.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cpd/10.2174/0113816128344629250115074105
2025-02-10
2025-03-30

  • From This Site

    /content/journals/cpd/10.2174/0113816128344629250115074105
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Ben-Shlomo Y. Darweesh S. Llibre-Guerra J. Marras C. San Luciano M. Tanner C. The epidemiology of Parkinson’s disease. Lancet 2024 403 10423 283 292 10.1016/S0140‑6736(23)01419‑8 38245248
    [Google Scholar]
  2. Morris H.R. Spillantini M.G. Sue C.M. Williams-Gray C.H. The pathogenesis of Parkinson’s disease. Lancet 2024 403 10423 293 304 10.1016/S0140‑6736(23)01478‑2 38245249
    [Google Scholar]
  3. Lv Q.K. Tao K.X. Wang X.B. Yao X.Y. Pang M.Z. Liu J.Y. Wang F. Liu C.F. Role of α-synuclein in microglia: autophagy and phagocytosis balance neuroinflammation in Parkinson’s disease. Inflamm. Res. 2023 72 3 443 462 10.1007/s00011‑022‑01676‑x 36598534
    [Google Scholar]
  4. Zhang W.D. Li N. Du Z.R. Zhang M. Chen S. Chen W.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. 2021 906 174269 10.1016/j.ejphar.2021.174269 34147477
    [Google Scholar]
  5. Zhang H. Wang H. Wei J. Chen X. Sun M. Ouyang H. Hao J. Chang Y. Dou Z. He J. Comparison of the active compositions between raw and processed epimedium from different species. Molecules 2018 23 7 1656 10.3390/molecules23071656 29986486
    [Google Scholar]
  6. Liu F.Y. Ding D.N. Wang Y.R. Liu S.X. Peng C. Shen F. Zhu X.Y. Li C. Tang L.P. Han F.J. Icariin as a potential anticancer agent: A review of its biological effects on various cancers. Front. Pharmacol. 2023 14 1216363 10.3389/fphar.2023.1216363 37456751
    [Google Scholar]
  7. Ma Y. Zhao C. Hu H. Yin S. Liver protecting effects and molecular mechanisms of icariin and its metabolites. Phytochemistry 2023 215 113841 10.1016/j.phytochem.2023.113841 37660725
    [Google Scholar]
  8. Jiang W. Ding K. Yue R. Lei M. Therapeutic effects of icariin and icariside II on diabetes mellitus and its complications. Crit. Rev. Food Sci. Nutr. 2023 1 26 36591787
    [Google Scholar]
  9. Zheng L. Wu S. Jin H. Wu J. Wang X. Cao Y. Zhou Z. Jiang Y. Li L. Yang X. Shen Q. Guo S. Shen Y. Li C. Ji L. Molecular mechanisms and therapeutic potential of icariin in the treatment of Alzheimer’s disease. Phytomedicine 2023 116 154890 10.1016/j.phymed.2023.154890 37229892
    [Google Scholar]
  10. Wang Y. Shang C. Zhang Y. Xin L. Jiao L. Xiang M. Shen Z. Chen C. Ding F. Lu Y. Cui X. Regulatory mechanism of icariin in cardiovascular and neurological diseases. Biomed. Pharmacother. 2023 158 114156 10.1016/j.biopha.2022.114156 36584431
    [Google Scholar]
  11. Liu S. Liu C.M. Lai L.J. Li L.D. Progress in the study of the pharmacological effects of Icaritin. J. Gannan Med. Uni. 2017 37 04 631 635
    [Google Scholar]
  12. Xiao Q. Fan H.J. Li Y.R. Sun R.R. Jia L. Xu L. Wei J.Z. Xiao B.G. Ma C.G. Cai Z. Advances in Parkinson’s disease pathogenesis. Med. J. Chinese People’s Liberation Army. 2023 48 08 983 992
    [Google Scholar]
  13. Isik S. Yeman Kiyak B. Akbayir R. Seyhali R. Arpaci T. Microglia mediated neuroinflammation in parkinson’s disease. Cells 2023 12 7 1012 10.3390/cells12071012 37048085
    [Google Scholar]
  14. Yu H. Chang Q. Sun T. He X. Wen L. An J. Feng J. Zhao Y. Metabolic reprogramming and polarization of microglia in Parkinson’s disease: Role of inflammasome and iron. Ageing Res. Rev. 2023 90 102032 10.1016/j.arr.2023.102032 37572760
    [Google Scholar]
  15. Patani R. Hardingham G.E. Liddelow S.A. Functional roles of reactive astrocytes in neuroinflammation and neurodegeneration. Nat. Rev. Neurol. 2023 19 7 395 409 10.1038/s41582‑023‑00822‑1 37308616
    [Google Scholar]
  16. Yang Y. Jiang G.Y. Jin M.R. Li J.J. Liu Z.M. Chen W.F. Neuronal damage caused by lipopolysaccharide-activated mesencephalon glial cell-conditioned medium and the neuroprotective effect of icaritin. J. Qingdao Uni. (Med. Sci.). 2021 57 02 182 185
    [Google Scholar]
  17. Wu H. Liu X. Gao Z.Y. Lin M. Zhao X. Sun Y. Pu X.P. Icaritin provides neuroprotection in parkinson’s disease by attenuating neuroinflammation, oxidative stress, and energy deficiency. Antioxidants 2021 10 4 529 10.3390/antiox10040529 33805302
    [Google Scholar]
  18. Hwang E. Lin P. Ngo H.T.T. Gao W. Wang Y.S. Yu H.S. Yi T.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. 2018 17 10 1396 1408 10.1039/c8pp00174j 30225503
    [Google Scholar]
  19. Arterburn J.B. Prossnitz E.R. G protein–coupled estrogen receptor GPER: Molecular pharmacology and therapeutic applications. Annu. Rev. Pharmacol. Toxicol. 2023 63 1 295 320 10.1146/annurev‑pharmtox‑031122‑121944 36662583
    [Google Scholar]
  20. Prossnitz E.R. Barton M. The G protein-coupled oestrogen receptor GPER in health and disease: An update. Nat. Rev. Endocrinol. 2023 19 7 407 424 10.1038/s41574‑023‑00822‑7 37193881
    [Google Scholar]
  21. Fender D. Harper W.M. Gregg P.J. The Trent regional arthroplasty study. J. Bone Joint Surg. Br. 2000 82-B 7 944 947 10.1302/0301‑620X.82B7.0820944 11041579
    [Google Scholar]
  22. Yu T. Yang G. Hou Y. Tang X. Wu C. Wu X. Guo L. Zhu Q. Luo H. Du Y. Wen S. Xu L. Yin J. Tu G. Liu M. Cytoplasmic GPER translocation in cancer-associated fibroblasts mediates cAMP/PKA/CREB/glycolytic axis to confer tumor cells with multidrug resistance. Oncogene 2017 36 15 2131 2145 10.1038/onc.2016.370 27721408
    [Google Scholar]
  23. Kilpatrick L.E. Hill S.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. 2021 16 102 112 10.1016/j.coemr.2020.10.003 33748531
    [Google Scholar]
  24. Yu Z. Su G. Zhang L. Liu G. Zhou Y. Fang S. Zhang Q. Wang T. Huang C. Huang Z. Li L. Icaritin inhibits neuroinflammation in a rat cerebral ischemia model by regulating microglial polarization through the GPER–ERK–NF-κB signaling pathway. Mol. Med. 2022 28 1 142 10.1186/s10020‑022‑00573‑7 36447154
    [Google Scholar]
  25. Yao W. Tao R. Wang K. Ding X. Icariin attenuates vascular endothelial dysfunction by inhibiting inflammation through GPER/Sirt1/HMGB1 signaling pathway in type 1 diabetic rats. Chin. J. Nat. Med. 2024 22 4 293 306 10.1016/S1875‑5364(24)60618‑7 38658093
    [Google Scholar]
  26. Yang Y. Experimental study of the anti-inflammatory response to icariin and icaritin via GPER in Parkinson's disease. 2022 Qingdao University
    [Google Scholar]
  27. Guan J. Yang B. Fan Y. Zhang J. GPER agonist G1 attenuates neuroinflammation and dopaminergic neurodegeneration in parkinson disease. Neuroimmunomodulation 2017 24 1 60 66 10.1159/000478908 28810246
    [Google Scholar]
  28. Mendes-Oliveira J. Lopes Campos F. Videira R.A. Baltazar G. GPER activation is effective in protecting against inflammation-induced nigral dopaminergic loss and motor function impairment. Brain Behav. Immun. 2017 64 296 307 10.1016/j.bbi.2017.04.016 28450223
    [Google Scholar]
  29. Jiang M.C. Chen X.H. Zhao X. Zhang X.J. Chen W.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. 2016 786 53 59 10.1016/j.ejphar.2016.05.031 27238975
    [Google Scholar]
  30. Mishra E. Thakur M.K. Mitophagy: A promising therapeutic target for neuroprotection during ageing and age‐related diseases. Br. J. Pharmacol. 2023 180 12 1542 1561 10.1111/bph.16062 36792062
    [Google Scholar]
  31. Von Stockum S. Nardin A. Schrepfer E. Ziviani E. Mitochondrial dynamics and mitophagy in Parkinson’s disease: A fly point of view. Neurobiol. Dis. 2016 90 58 67 10.1016/j.nbd.2015.11.002 26550693
    [Google Scholar]
  32. Burté F. Carelli V. Chinnery P.F. Yu-Wai-Man P. Disturbed mitochondrial dynamics and neurodegenerative disorders. Nat. Rev. Neurol. 2015 11 1 11 24 10.1038/nrneurol.2014.228 25486875
    [Google Scholar]
  33. Elfawy H.A. Das B. Crosstalk between mitochondrial dysfunction, oxidative stress, and age related neurodegenerative disease: Etiologies and therapeutic strategies. Life Sci. 2019 218 165 184 10.1016/j.lfs.2018.12.029 30578866
    [Google Scholar]
  34. Onyango I.G. Lu J. Rodova M. Lezi E. Crafter A.B. Swerdlow R.H. Regulation of neuron mitochondrial biogenesis and relevance to brain health. Biochim. Biophys. Acta Mol. Basis Dis. 2010 1802 1 228 234 10.1016/j.bbadis.2009.07.014 19682571
    [Google Scholar]
  35. Chen Y. Zhu G. Yuan T. Ma R. Zhang X. Meng F. Yang A. Du T. Zhang J. Subthalamic nucleus deep brain stimulation alleviates oxidative stress via mitophagy in Parkinson’s disease. NPJ Parkinsons Dis. 2024 10 1 52 10.1038/s41531‑024‑00668‑4 38448431
    [Google Scholar]
  36. Jomova K. Raptova R. Alomar S.Y. Alwasel S.H. Nepovimova E. Kuca K. Valko M. Reactive oxygen species, toxicity, oxidative stress, and antioxidants: Chronic diseases and aging. Arch. Toxicol. 2023 97 10 2499 2574 10.1007/s00204‑023‑03562‑9 37597078
    [Google Scholar]
  37. Teleanu D.M. Niculescu A.G. Lungu I.I. Radu C.I. Vladâcenco O. Roza E. Costăchescu B. Grumezescu A.M. Teleanu R.I. An overview of oxidative stress, neuroinflammation, and neurodegenerative diseases. Int. J. Mol. Sci. 2022 23 11 5938 10.3390/ijms23115938 35682615
    [Google Scholar]
  38. Park J.S. Davis R.L. Sue C.M. Mitochondrial dysfunction in parkinson’s disease: New mechanistic insights and therapeutic perspectives. Curr. Neurol. Neurosci. Rep. 2018 18 5 21 10.1007/s11910‑018‑0829‑3 29616350
    [Google Scholar]
  39. Franco-Iborra S. Vila M. Perier C. Mitochondrial quality control in neurodegenerative diseases: Focus on parkinson’s disease and huntington’s disease. Front. Neurosci. 2018 12 342 10.3389/fnins.2018.00342 29875626
    [Google Scholar]
  40. Ganguly G. Chakrabarti S. Chatterjee U. Saso L. Proteinopathy, oxidative stress and mitochondrial dysfunction: cross talk in Alzheimer’s disease and Parkinson’s disease. Drug Des. Devel. Ther. 2017 11 797 810 10.2147/DDDT.S130514 28352155
    [Google Scholar]
  41. Klemmensen M.M. Borrowman S.H. Pearce C. Pyles B. Chandra B. Mitochondrial dysfunction in neurodegenerative disorders. Neurotherapeutics 2024 21 1 e00292 10.1016/j.neurot.2023.10.002 38241161
    [Google Scholar]
  42. Du X. Xie X. Liu R. The role of α-synuclein oligomers in parkinson’s disease. Int. J. Mol. Sci. 2020 21 22 8645 10.3390/ijms21228645 33212758
    [Google Scholar]
  43. Liu C. Ding X. Guo X. Zhao M. Zhang X. Li Z. Zhao R. Cao Y. Xing J. Recombinant human HspB5-ACD structural domain inhibits neurotoxicity by regulating pathological α-Syn aggregation. Int. J. Biol. Macromol. 2024 255 128311 10.1016/j.ijbiomac.2023.128311 37992927
    [Google Scholar]
  44. Sommer S.P. Sommer S. Sinha B. Walter D. Aleksic I. Gohrbandt B. Otto C. Leyh R.G. Glutathione preconditioning ameliorates mitochondria dysfunction during warm pulmonary ischemia-reperfusion injury. Eur. J. Cardiothorac. Surg. 2012 41 1 140 148 21596579
    [Google Scholar]
  45. Picca A. Guerra F. Calvani R. Romano R. Coelho-Júnior H.J. Bucci C. Marzetti E. Mitochondrial dysfunction, protein misfolding and neuroinflammation in parkinson’s disease: Roads to biomarker discovery. Biomolecules 2021 11 10 1508 10.3390/biom11101508 34680141
    [Google Scholar]
  46. Zhou X. Huang N. Hou X. Zhu L. Xie Y. Ba Z. Luo Y. Icaritin attenuates 6-OHDA-induced MN9D cell damage by inhibiting oxidative stress. PeerJ 2022 10 e13256 10.7717/peerj.13256 35433120
    [Google Scholar]
  47. Li Q. Huai L. Zhang C. Wang C. Jia Y. Chen Y. Yu P. Wang H. Rao Q. Wang M. Wang J. Icaritin induces AML cell apoptosis via the MAPK/ERK and PI3K/AKT signal pathways. Int. J. Hematol. 2013 97 5 617 623 10.1007/s12185‑013‑1317‑9 23550021
    [Google Scholar]
  48. Lou Y. Zou L. Shen Z. Zheng J. Lin Y. Zhang Z. Chen X. Pan J. Zhang X. Protective effect of dexmedetomidine against delayed bone healing caused by morphine via PI3K/Akt mediated Nrf2 antioxidant defense system. Front. Pharmacol. 2024 15 1396713 10.3389/fphar.2024.1396713 38863982
    [Google Scholar]
  49. Ulasov A.V. Rosenkranz A.A. Georgiev G.P. Sobolev A.S. Nrf2/Keap1/ARE signaling: Towards specific regulation. Life Sci. 2022 291 120111 10.1016/j.lfs.2021.120111 34732330
    [Google Scholar]
  50. Chen G.H. Song C.C. Pantopoulos K. Wei X.L. Zheng H. Luo Z. Mitochondrial oxidative stress mediated Fe-induced ferroptosis via the NRF2-ARE pathway. Free Radic. Biol. Med. 2022 180 95 107 10.1016/j.freeradbiomed.2022.01.012 35045311
    [Google Scholar]
  51. Dinkova-Kostova AT Abramov AY The emerging role of Nrf2 in mitochondrial function. Free Radic Biol Med 2015 88 Pt B 179 188 10.1016/j.freeradbiomed.2015.04.036 25975984
    [Google Scholar]
  52. Vasconcelos A.R. dos Santos N.B. Scavone C. Munhoz C.D. Nrf2/ARE pathway modulation by dietary energy regulation in neurological disorders. Front. Pharmacol. 2019 10 33 10.3389/fphar.2019.00033 30778297
    [Google Scholar]
  53. Zhang B. Wang G. He J. Yang Q. Li D. Li J. Zhang F. Icariin attenuates neuroinflammation and exerts dopamine neuroprotection via an Nrf2-dependent manner. J. Neuroinflammation 2019 16 1 92 10.1186/s12974‑019‑1472‑x 31010422
    [Google Scholar]
  54. Wu J. Xu H. Wong P.F. Xia S. Xu J. Dong J. Icaritin attenuates cigarette smoke-mediated oxidative stress in human lung epithelial cells via activation of PI3K-AKT and Nrf2 signaling. Food Chem. Toxicol. 2014 64 307 313 10.1016/j.fct.2013.12.006 24333105
    [Google Scholar]
  55. Martínez-Limón A. Joaquin M. Caballero M. Posas F. de Nadal E. The p38 pathway: From biology to cancer therapy. Int. J. Mol. Sci. 2020 21 6 1913 10.3390/ijms21061913 32168915
    [Google Scholar]
  56. Gravandi M.M. Abdian S. Tahvilian M. Iranpanah A. Moradi S.Z. Fakhri S. Echeverría J. Therapeutic targeting of Ras/Raf/MAPK pathway by natural products: A systematic and mechanistic approach for neurodegeneration. Phytomedicine 2023 115 154821 10.1016/j.phymed.2023.154821 37119761
    [Google Scholar]
  57. Pyakurel A. Savoia C. Hess D. Scorrano L. Extracellular regulated kinase phosphorylates mitofusin 1 to control mitochondrial morphology and apoptosis. Mol. Cell 2015 58 2 244 254 10.1016/j.molcel.2015.02.021 25801171
    [Google Scholar]
  58. Bohush A. Niewiadomska G. Filipek A. Role of mitogen activated protein kinase signaling in parkinson’s disease. Int. J. Mol. Sci. 2018 19 10 2973 10.3390/ijms19102973 30274251
    [Google Scholar]
  59. Iba M. Kim C. Kwon S. Szabo M. Horan-Portelance L. Peer C.J. Figg W.D. Reed X. Ding J. Lee S.J. Rissman R.A. Cookson M.R. Overk C. Wrasidlo W. Masliah E. Inhibition of p38α MAPK restores neuronal p38γ MAPK and ameliorates synaptic degeneration in a mouse model of DLB/PD. Sci. Transl. Med. 2023 15 695 eabq6089 10.1126/scitranslmed.abq6089 37163617
    [Google Scholar]
  60. Mattson M.P. Neuronal life-and-death signaling, apoptosis, and neurodegenerative disorders. Antioxid. Redox Signal. 2006 8 11-12 1997 2006 10.1089/ars.2006.8.1997 17034345
    [Google Scholar]
  61. Novikova L. Garris B.L. Garris D.R. Lau Y.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. Neuroscience 2006 140 1 67 76 10.1016/j.neuroscience.2006.02.007 16533572
    [Google Scholar]
  62. Ghavami S. Shojaei S. Yeganeh B. Ande S.R. Jangamreddy J.R. Mehrpour M. Christoffersson J. Chaabane W. Moghadam A.R. Kashani H.H. Hashemi M. Owji A.A. Łos M.J. Autophagy and apoptosis dysfunction in neurodegenerative disorders. Prog. Neurobiol. 2014 112 24 49 10.1016/j.pneurobio.2013.10.004 24211851
    [Google Scholar]
  63. Fuchs Y. Steller H. Programmed cell death in animal development and disease. Cell 2011 147 4 742 758 10.1016/j.cell.2011.10.033 22078876
    [Google Scholar]
  64. Qiao C. Ye W. Li S. Wang H. Ding X. Icariin modulates mitochondrial function and apoptosis in high glucose-induced glomerular podocytes through G protein-coupled estrogen receptors. Mol. Cell. Endocrinol. 2018 473 146 155 10.1016/j.mce.2018.01.014 29373840
    [Google Scholar]
  65. Wang K. Zheng X. Pan Z. Yao W. Gao X. Wang X. Ding X. 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. 2020 8 559 10.3389/fcell.2020.00559 32766240
    [Google Scholar]
/content/journals/cpd/10.2174/0113816128344629250115074105
Loading
Therapeutic Effects and Mechanisms of Icaritin in Parkinson's Disease
Bentham Science Publishers ; https://doi.org/10.2174/0113816128344629250115074105
/content/journals/cpd/10.2174/0113816128344629250115074105
/content/journals/cpd/10.2174/0113816128344629250115074105
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: neuroprotection ; Parkinson's disease ; icaritin ; neuroinflammation ; oxidative stress

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test