Review Volume 14, Issue 3 pp 1562—1588

The neuroprotective effects of icariin on ageing, various neurological, neuropsychiatric disorders, and brain injury induced by radiation exposure

Ling Rui Li1, *, , Gautam Sethi2, *, , Xing Zhang1, , Cui Liu Liu1, , Yan Huang1, , Qun Liu1, , Bo Xu Ren1, , Feng Ru Tang3, ,

  • 1 The School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou 434023, Hubei, China
  • 2 Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore
  • 3 Radiation Physiology Lab, Singapore Nuclear Research and Safety Initiative, National University of Singapore, Singapore 138602, Singapore
* Equal contribution

Received: October 18, 2021       Accepted: February 8, 2022       Published: February 14, 2022
How to Cite

Copyright: © 2022 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Epimedium brevicornum Maxim, a Traditional Chinese Medicine, has been used for the treatment of impotence, sinew and bone disorders, “painful impediment caused by wind-dampness,” numbness, spasms, hypertension, coronary heart disease, menopausal syndrome, bronchitis, and neurasthenia for many years in China. Recent animal experimental studies indicate that icariin, a major bioactive component of epimedium may effectively treat Alzheimer’s disease, cerebral ischemia, depression, Parkinson’s disease, multiple sclerosis, as well as delay ageing. Our recent study also suggested that epimedium extract could exhibit radio-neuro-protective effects and prevent ionizing radiation-induced impairment of neurogenesis. This paper reviewed the pharmacodynamics of icariin in treating different neurodegenerative and neuropsychiatric diseases, ageing, and radiation-induced brain damage. The relevant molecular mechanisms and its anti-neuroinflammatory, anti-apoptotic, anti-oxidant, as well as pro-neurogenesis roles were also discussed.


TCM: Traditional Chinese Medicine; CRH: corticotropin releasing hormone; SAMP8: senescence accelerated mouse prone 8; AD: Alzheimer’s disease; Aβ: amyloid-beta; Bcl-2: B-cell lymphoma 2; NaN3: sodium azide; PI3K: phosphoinositide 3-kinase; Akt: protein kinase B; GSK-3β: glycogen synthase kinase-3β; CNS: central nervous system; PD: Parkinson’s disease; MS: multiple sclerosis; MND: Motor neuron diseases; SCA: Spinocerebellar ataxia; HD: Huntington’s disease; APP: amyloid precursor protein; BACE1: β-site APP-cleaving enzyme 1; 2-VO: permanent bilateral ligation of the common carotid arteries; SOD: superoxide dismutase; MDA: malondialdehyde; NO: nitric oxide; sGC: soluble guanylate cyclase; cGMP: cyclic guanosine monophosphate; PKG: protein kinase G; CREB: cyclic adenine monophosphate responsive element binding protein; PDE5: Phosphodiesterase 5; MPTP: 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine; DA: dopaminergic; SNpc: substantia nigra pars compacta; MEK: mitogen-activated protein kinase kinase; ERK: extracellular signal-regulated kinase; LPS: lipopolysaccharide; 6-OHDA: 6-hydroxydopamine; TNF-α: tumor necrosis factor-α; IL-1β: interleukin-1β; NF-ĸB: nuclear factor-ĸB; Nrf2: Nuclear factor erythroid 2 related factor 2; I/R: ischemia-reperfusion; MACO: middle cerebral artery occlusion; PPAR: peroxisome proliferator-activated receptors; OGD: oxygen and glucose deprivation; OGD/R: oxygen-glucose deprivation and reperfusion; SIRT: Sirtuin; MAPK: mitogen-activated protein kinase; PGC-1α: peroxisome proliferator-activated receptor γ coactivator-1α; HPA: hypothalamic-pituitary-adrenal; CMS: chronic mild stress; CRF: corticotropin-releasing factor; CORT: corticosterone; CUMS: chronic unpredictable mild stress; FKBP5: FK506 binding protein 5; SGK-1: glucocorticoid-inducible kinase 1; IL-6: interleukin-6; BDNF: brain-derived neurotrophic factor; PGE: prostaglandin E; COX-2: cyclooxygenase-2; TAK1: TGF-β activated kinase-1; IKK: IκB kinase; NLRP3: nod-like receptor protein 3; HMGB1: High mobility group protein box 1; PRS: prenatal restraint stress; EAAT2: excitatory amino acid transporter 2; mGluR: metabotropic glutamate receptor; UVB: ultraviolet radiation B; EAE: experimental autoimmune encephalomyelitis; SA-β-gal: senescence-associated β-galactosidase; NAD+: Nicotinamide adenine nucleotide; C. elegans: Caenorhabditis elegans; CT: computed tomography; PET: positron emission tomography; FDA: US Food and Drug Administration; MSCs: mesenchymal stem cells; SGZ: subgranular zone; DG: dentate gyrus; ROT: Rotenone; icv: intracerebroventricular; OGD/R: oxygen-glucose deprivation and reperfusion; ER: endoplasmic reticulum; PERK: protein kinase RNA-like ER kinase; Eif2α: eukaryotic initiation factor 2α; H2O2: hydrogen peroxide; IRE1: inositol-requiring enzyme-1; XBP1: X-box-binding protein-1; ROS: reactive oxygen species; RAGE: receptor for advanced glycation end products; NSCs: neural stem cells; SVZ: subventricular zone; LTP: long-term potentiation; CaMKIIα: Ca2+/calmodulin-dependent protein kinase II alpha; MWM: Morris water maze; NGSTH: nanogel loaded self-assembled thermosensitive hydrogel; HSYA: hydroxysafflor yellow A; lncRNA: Lon non-coding RNA.