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Abstract

Introduction

Neuroinflammation plays a pivotal role in diabetes-associated cognitive dysfunction. Icariin (ICA), a bioactive flavonoid from Epimedium, shows neuroprotective potential, though its mechanism remains unclear.

Methods

Potential ICA targets and diabetic cognitive impairment-related genes were identified through database mining. A protein-protein interaction network was constructed (STRING database) and analyzed (Cytoscape) to identify hub genes. Molecular docking and dynamics simulations validated key targets, followed by validation using high glucose-induced HT22 cells.

Results

Network pharmacology suggested ICA's neuroprotection involves MAPK pathway modulation and anti-inflammatory effects. studies confirmed ICA suppressed pro-inflammatory cytokine release and regulated MAPK signaling.

Discussion

ICA's neuroprotection aligns with known flavonoid anti-inflammatory properties. However, limitations include single-cell line use and potentially non-physiological concentrations. Future studies should assess ICA in diabetic animal models, blood-brain barrier penetration, and synergy with antidiabetic drugs.

Conclusion

ICA protects HT22 cells from high glucose-induced damage MAPK signaling and reduces inflammation, suggesting therapeutic potential for diabetic cognitive impairment. Further validation is warranted.

© 2025 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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2025-10-07
2025-11-13

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References

  1. Biessels G.J. Whitmer R.A. Cognitive dysfunction in diabetes: How to implement emerging guidelines. Diabetologia 2020 63 1 3 9 10.1007/s00125‑019‑04977‑9 31420699
    [Google Scholar]
  2. Biessels G.J. Reagan L.P. Hippocampal insulin resistance and cognitive dysfunction. Nat. Rev. Neurosci. 2015 16 11 660 671 10.1038/nrn4019 26462756
    [Google Scholar]
  3. Jiang T. Li Y. He S. Reprogramming astrocytic NDRG2/NF-κB/C3 signaling restores the diabetes-associated cognitive dysfunction. EBioMedicine 2023 93 104653 10.1016/j.ebiom.2023.104653 37329577
    [Google Scholar]
  4. Jones N. Riby L. Mitchell R. Smith M. Type 2 diabetes and memory: Using neuroimaging to understand the mechanisms. Curr. Diabetes Rev. 2014 10 2 118 123 10.2174/1573399810666140425160811 24766069
    [Google Scholar]
  5. den Heijer T. Vermeer S.E. van Dijk E.J. Type 2 diabetes and atrophy of medial temporal lobe structures on brain MRI. Diabetologia 2003 46 12 1604 1610 10.1007/s00125‑003‑1235‑0 14595538
    [Google Scholar]
  6. Biessels G.J. Despa F. Cognitive decline and dementia in diabetes mellitus: Mechanisms and clinical implications. Nat. Rev. Endocrinol. 2018 14 10 591 604 10.1038/s41574‑018‑0048‑7 30022099
    [Google Scholar]
  7. Cheng G. Huang C. Deng H. Wang H. Diabetes as a risk factor for dementia and mild cognitive impairment: A meta‐analysis of longitudinal studies. Intern. Med. J. 2012 42 5 484 491 10.1111/j.1445‑5994.2012.02758.x 22372522
    [Google Scholar]
  8. Exalto L.G. Biessels G.J. Karter A.J. Risk score for prediction of 10 year dementia risk in individuals with type 2 diabetes: A cohort study. Lancet Diabetes Endocrinol. 2013 1 3 183 190 10.1016/S2213‑8587(13)70048‑2 24622366
    [Google Scholar]
  9. Brands A.M.A. Biessels G.J. de Haan E.H.F. Kappelle L.J. Kessels R.P.C. The effects of type 1 diabetes on cognitive performance: A meta-analysis. Diabetes Care 2005 28 3 726 735 10.2337/diacare.28.3.726 15735218
    [Google Scholar]
  10. Wrighten S.A. Piroli G.G. Grillo C.A. Reagan L.P. A look inside the diabetic brain: Contributors to diabetes-induced brain aging. Biochim. Biophys. Acta Mol. Basis Dis. 2009 1792 5 444 453 10.1016/j.bbadis.2008.10.013 19022375
    [Google Scholar]
  11. Okereke O.I. Kang J.H. Cook N.R. Type 2 diabetes mellitus and cognitive decline in two large cohorts of community-dwelling older adults. J. Am. Geriatr. Soc. 2008 56 6 1028 1036 10.1111/j.1532‑5415.2008.01686.x 18384580
    [Google Scholar]
  12. Brands A.M.A. Biessels G.J. Kappelle L.J. Cognitive functioning and brain MRI in patients with type 1 and type 2 diabetes mellitus: A comparative study. Dement. Geriatr. Cogn. Disord. 2007 23 5 343 350 10.1159/000100980 17374953
    [Google Scholar]
  13. Nagayach A. Bhaskar R. Patro I. Microglia activation and inflammation in hippocampus attenuates memory and mood functions during experimentally induced diabetes in rat. J. Chem. Neuroanat. 2022 125 102160 10.1016/j.jchemneu.2022.102160 36089179
    [Google Scholar]
  14. Stranahan A.M. Hao S. Dey A. Yu X. Baban B. Blood–brain barrier breakdown promotes macrophage infiltration and cognitive impairment in leptin receptor-deficient mice. J. Cereb. Blood Flow Metab. 2016 36 12 2108 2121 10.1177/0271678X16642233 27034250
    [Google Scholar]
  15. Xu T. Liu J. Li X. The mTOR/NF-κB pathway mediates neuroinflammation and synaptic plasticity in diabetic encephalopathy. Mol. Neurobiol. 2021 58 8 3848 3862 10.1007/s12035‑021‑02390‑1 33860440
    [Google Scholar]
  16. Suzuki M. Umegaki H. Ieda S. Mogi N. Iguchi A. Factors associated with cognitive impairment in elderly patients with diabetes mellitus. J. Am. Geriatr. Soc. 2006 54 3 558 559 10.1111/j.1532‑5415.2006.00643_11.x 16551341
    [Google Scholar]
  17. Ma S. Bi W. Liu X. Single-cell sequencing analysis of the db/db mouse hippocampus reveals cell-type-specific insights into the pathobiology of diabetes-associated cognitive dysfunction. Front. Endocrinol. 2022 13 891039 10.3389/fendo.2022.891039 35721719
    [Google Scholar]
  18. Lu F. Li L. Zheng B. Icariin alleviates cognitive dysfunction by reducing neuroinflammation via the cGAS-STING pathway. J. Ethnopharmacol. 2025 350 120010 10.1016/j.jep.2025.120010 40403897
    [Google Scholar]
  19. Lei X. Wen D. Huang Z. Icariin attenuates oxidative stress via SIRT1/PGC-1α pathway in SAH mice. Exp. Neurol. 2025 390 115303 10.1016/j.expneurol.2025.115303 40345568
    [Google Scholar]
  20. Liu Z.Q. Luo X.Y. Sun Y.X. The antioxidative effect of icariin in human erythrocytes against free-radical-induced haemolysis. J. Pharm. Pharmacol. 2004 56 12 1557 1562 10.1211/0022357044869 15563763
    [Google Scholar]
  21. 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]
  22. Zheng H. Qu L. Yang L. Xie X. Song L. Xie Q. An injectable hydrogel loaded with Icariin attenuates cartilage damage in rabbit knee osteoarthritis via Wnt/β-catenin signaling pathway. Int. Immunopharmacol. 2025 145 113725 10.1016/j.intimp.2024.113725 39667046
    [Google Scholar]
  23. Ma D. Zhu Z. Tan X. Validation of peripheral neuromodulation mechanisms of Icariin in knee osteoarthritis–related chronic pain. J. Cell. Mol. Med. 2024 28 23 e70223 10.1111/jcmm.70223 39622788
    [Google Scholar]
  24. Xiao J. Luo C. Li A. Icariin inhibits chondrocyte ferroptosis and alleviates osteoarthritis by enhancing the SLC7A11/GPX4 signaling. Int. Immunopharmacol. 2024 133 112010 10.1016/j.intimp.2024.112010 38636375
    [Google Scholar]
  25. Zou J. peng, wang, Xu, Shi C, Liu Q. Icariin ameliorates osteoporosis by activating autophagy in ovariectomized rats. Adv. Clin. Exp. Med. 2024 33 9 941 952 10.17219/acem/174078 38235994
    [Google Scholar]
  26. Xiang S. Zhao L. Tang C. Icariin inhibits osteoblast ferroptosis via Nrf2/HO-1 signaling and enhances healing of osteoporotic fractures. Eur. J. Pharmacol. 2024 965 176244 10.1016/j.ejphar.2023.176244 38092316
    [Google Scholar]
  27. Zhao F. Chen H. Wang S. Effects of icariin as a feed additive on the reproductive function in bucks (Capra hircus). Front. Vet. Sci. 2024 11 1467947 10.3389/fvets.2024.1467947 39575435
    [Google Scholar]
  28. Liu F. Liao B. Ling Y.L. Icariin protects testicular damage in streptozotocin-induced diabetic rats through regulation of glycolysis pathway. Int. J. Immunopathol. Pharmacol. 2024 38 03946320241279525 10.1177/03946320241279525 39180223
    [Google Scholar]
  29. Lu C.S. Wu C.Y. Wang Y.H. The protective effects of icariin against testicular dysfunction in type 1 diabetic mice via AMPK-mediated Nrf2 activation and NF-κB p65 inhibition. Phytomedicine 2024 123 155217 10.1016/j.phymed.2023.155217 37992492
    [Google Scholar]
  30. Yao W. Tao R. Xu Y. Chen Z.S. Ding X. Wan L. AR/RKIP pathway mediates the inhibitory effects of icariin on renal fibrosis and endothelial-to-mesenchymal transition in type 2 diabetic nephropathy. J. Ethnopharmacol. 2024 320 117414 10.1016/j.jep.2023.117414 37977422
    [Google Scholar]
  31. Zhao Y. Yang W. Zhang X. Lv C. Lu J. Icariin, the main prenylflavonoid of Epimedii Folium, ameliorated chronic kidney disease by modulating energy metabolism via AMPK activation. J. Ethnopharmacol. 2023 312 116543 10.1016/j.jep.2023.116543 37088241
    [Google Scholar]
  32. Liu B. Xu C. Wu X. Icariin exerts an antidepressant effect in an unpredictable chronic mild stress model of depression in rats and is associated with the regulation of hippocampal neuroinflammation. Neuroscience 2015 294 193 205 10.1016/j.neuroscience.2015.02.053 25791226
    [Google Scholar]
  33. Wang G.Q. Li D.D. Huang C. RETRACTED: Icariin reduces dopaminergic neuronal loss and microglia-mediated inflammation in vivo and in vitro. Front. Mol. Neurosci. 2018 10 441 10.3389/fnmol.2017.00441 29375304
    [Google Scholar]
  34. Khezri M.R. Ghasemnejad-Berenji M. Icariin: A potential neuroprotective agent in Alzheimer’s disease and Parkinson’s disease. Neurochem. Res. 2022 47 10 2954 2962 10.1007/s11064‑022‑03667‑0 35802286
    [Google Scholar]
  35. Ru J. Li P. Wang J. TCMSP: A database of systems pharmacology for drug discovery from herbal medicines. J. Cheminform. 2014 6 1 13 10.1186/1758‑2946‑6‑13 24735618
    [Google Scholar]
  36. Amberger J.S. Bocchini C.A. Schiettecatte F. Scott A.F. Hamosh A. OMIM.org: Online Mendelian Inheritance in Man (OMIM®), an online catalog of human genes and genetic disorders. Nucleic Acids Res. 2015 43 D1 D789 D798 10.1093/nar/gku1205 25428349
    [Google Scholar]
  37. Szklarczyk D. Kirsch R. Koutrouli M. The STRING database in 2023: Protein-protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res. 2023 51 D1 D638 D646 10.1093/nar/gkac1000 36370105
    [Google Scholar]
  38. Huang D.W. Sherman B.T. Lempicki R.A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 2009 4 1 44 57 10.1038/nprot.2008.211 19131956
    [Google Scholar]
  39. Liu Y. Grimm M. Dai W. Hou M. Xiao Z.X. Cao Y. CB-Dock: A web server for cavity detection-guided protein-ligand blind docking. Acta Pharmacol. Sin. 2020 41 1 138 144 10.1038/s41401‑019‑0228‑6 31263275
    [Google Scholar]
  40. Zhang K.S. Zhou Q. Wang Y.F. Liang L.J. Killing effects of different physical factors on extracorporeal HepG2 human hepatoma cells. Asian Pac. J. Cancer Prev. 2012 13 3 1025 1029 10.7314/APJCP.2012.13.3.1025 22631632
    [Google Scholar]
  41. Dong C. Davis R.J. Flavell R.A. MAP kinases in the immune response. Annu. Rev. Immunol. 2002 20 1 55 72 10.1146/annurev.immunol.20.091301.131133 11861597
    [Google Scholar]
  42. Duncan B.B. Schmidt M.I. The epidemiology of low-grade chronic systemic inflammation and type 2 diabetes. Diabetes Technol. Ther. 2006 8 1 7 17 10.1089/dia.2006.8.7 16472046
    [Google Scholar]
  43. De La Monte S.M. Insulin resistance and Alzheimer’s disease. BMB Rep. 2009 42 8 475 481 10.5483/BMBRep.2009.42.8.475 19712582
    [Google Scholar]
  44. Tuttle K.R. Linking metabolism and immunology: Diabetic nephropathy is an inflammatory disease. J. Am. Soc. Nephrol. 2005 16 6 1537 1538 10.1681/ASN.2005040393 15872083
    [Google Scholar]
  45. Wang Z. Huang Y. Cheng Y. Endoplasmic reticulum stress-induced neuronal inflammatory response and apoptosis likely plays a key role in the development of diabetic encephalopathy. Oncotarget 2016 7 48 78455 78472 10.18632/oncotarget.12925 27793043
    [Google Scholar]
  46. Jawale A. Datusalia A.K. Bishnoi M. Sharma S.S. Reversal of diabetes-induced behavioral and neurochemical deficits by cinnamaldehyde. Phytomedicine 2016 23 9 923 930 10.1016/j.phymed.2016.04.008 27387400
    [Google Scholar]
  47. Thomas G.M. Huganir R.L. MAPK cascade signalling and synaptic plasticity. Nat. Rev. Neurosci. 2004 5 3 173 183 10.1038/nrn1346 14976517
    [Google Scholar]
  48. Liu R.Y. Zhang Y. Smolen P. Cleary L.J. Byrne J.H. Defective synaptic plasticity in a model of Coffin–Lowry syndrome is rescued by simultaneously targeting PKA and MAPK pathways. Learn. Mem. 2022 29 12 435 446 10.1101/lm.053625.122 36446603
    [Google Scholar]
  49. Ojea Ramos S. Feld M. Fustiñana M.S. Contributions of extracellular-signal regulated kinase 1/2 activity to the memory trace. Front. Mol. Neurosci. 2022 15 988790 10.3389/fnmol.2022.988790 36277495
    [Google Scholar]
  50. Jayaraj R.L. Azimullah S. Beiram R. Jalal F.Y. Rosenberg G.A. Neuroinflammation: Friend and foe for ischemic stroke. J. Neuroinflammation 2019 16 1 142 10.1186/s12974‑019‑1516‑2 31291966
    [Google Scholar]
  51. Liu P. Zhou Y. Shi J. Myricetin improves pathological changes in 3×Tg-AD mice by regulating the mitochondria-NLRP3 inflammasome-microglia channel by targeting P38 MAPK signaling pathway. Phytomedicine 2023 115 154801 10.1016/j.phymed.2023.154801 37086707
    [Google Scholar]
  52. Han X. He G. Wang J. Xifeng Jiannao pill mitigates MPTP-induced neuronal apoptosis by reducing inflammation and oxidative stress via MAPK signaling. Metab. Brain Dis. 2025 40 4 170 10.1007/s11011‑025‑01597‑8 40183980
    [Google Scholar]
  53. Zhang X. Wang Y. Lv J. STAT4 targets KISS1 to inhibit the oxidative damage, inflammation and neuronal apoptosis in experimental PD models by inactivating the MAPK pathway. Neurochem. Int. 2024 175 105683 10.1016/j.neuint.2024.105683 38341034
    [Google Scholar]
  54. Jeong Y.H. Li W. Go Y. Oh Y.C. Atractylodis rhizoma alba attenuates neuroinflammation in BV2 microglia upon LPS stimulation by inducing HO-1 activity and inhibiting NF-κB and MAPK. Int. J. Mol. Sci. 2019 20 16 4015 10.3390/ijms20164015 31426492
    [Google Scholar]
  55. Plastira I. Bernhart E. Joshi L. MAPK signaling determines lysophosphatidic acid (LPA)-induced inflammation in microglia. J. Neuroinflammation 2020 17 1 127 10.1186/s12974‑020‑01809‑1 32326963
    [Google Scholar]
  56. Jie Z. Jing L. Jie C. Narirutin attenuates LPS-induced neuroinflammatory responses in both microglial cells and wild-type mice. Int. Immunopharmacol. 2025 159 114954 10.1016/j.intimp.2025.114954 40424653
    [Google Scholar]
  57. Huang L. Wang S. Zhang Q. Zhang J. Sun J. Fucosterol ameliorates depressive-like behaviours by suppressing microglial activation and neuroinflammation via inhibition the MAPK/ERK1/2 signaling pathway. Int. Immunopharmacol. 2025 158 114821 10.1016/j.intimp.2025.114821 40349406
    [Google Scholar]
  58. Liu Y. Zhai Y. Ma L. Colchicine alleviates ischemic white matter lesions and cognitive deficits by inhibiting microglia inflammation via the TAK1/MAPK/NF-κB signaling pathway. Behav. Brain Res. 2025 490 115619 10.1016/j.bbr.2025.115619 40334945
    [Google Scholar]
  59. Liu D. Zhu Y. Hou Z. Wang H. Li Q. Polysaccharides from Astragalus membranaceus Bunge alleviate LPS-induced neuroinflammation in mice by modulating microbe-metabolite-brain axis and MAPK/NF-κB signaling pathway. Int. J. Biol. Macromol. 2025 304 Pt 1 140885 10.1016/j.ijbiomac.2025.140885 39938846
    [Google Scholar]
  60. Sun J. Nan G. The extracellular signal-regulated kinase 1/2 pathway in neurological diseases: A potential therapeutic target Review. Int. J. Mol. Med. 2017 39 6 1338 1346 [ 10.3892/ijmm.2017.2962 28440493
    [Google Scholar]
  61. Shah S.A. Lee H.Y. Bressan R.A. Yun D.J. Kim M.O. Novel osmotin attenuates glutamate-induced synaptic dysfunction and neurodegeneration via the JNK/PI3K/Akt pathway in postnatal rat brain. Cell Death Dis. 2014 5 1 e1026 10.1038/cddis.2013.538 24481440
    [Google Scholar]
  62. Li T. Chen J. Xie Z. Ginsenoside Ro ameliorates cognitive impairment and neuroinflammation in APP/PS1 mice via the IBA1/GFAP-MAPK signaling pathway. Front. Pharmacol. 2025 16 1528590 10.3389/fphar.2025.1528590 40066331
    [Google Scholar]
  63. Liu Y. Xu X. Wu X. TMF attenuates cognitive impairment and neuroinflammation by inhibiting the MAPK/NF-κB pathway in Alzheimer’s disease: A multi-omics analysis. Mar. Drugs 2025 23 2 74 10.3390/md23020074 39997198
    [Google Scholar]
  64. Liu H. Zhou L. Wang X. PIEZO1 as a new target for hyperglycemic stress-induced neuropathic injury: The potential therapeutic role of bezafibrate. Biomed. Pharmacother. 2024 176 116837 10.1016/j.biopha.2024.116837 38815290
    [Google Scholar]
  65. Chen Q. Zheng Q. Yang Y. 12/15-lipoxygenase regulation of diabetic cognitive dysfunction is determined by interfering with inflammation and cell apoptosis. Int. J. Mol. Sci. 2022 23 16 8997 10.3390/ijms23168997 36012263
    [Google Scholar]
  66. Xia M. Zhang Y. Wu H. Forsythoside B attenuates neuro-inflammation and neuronal apoptosis by inhibition of NF-κB and p38-MAPK signaling pathways through activating Nrf2 post spinal cord injury. Int. Immunopharmacol. 2022 111 109120 10.1016/j.intimp.2022.109120 35944463
    [Google Scholar]
  67. Yoon S.Y. Park J.S. Choi J.E. Rosiglitazone reduces tau phosphorylation via JNK inhibition in the hippocampus of rats with type 2 diabetes and tau transfected SH-SY5Y cells. Neurobiol. Dis. 2010 40 2 449 455 10.1016/j.nbd.2010.07.005 20655383
    [Google Scholar]
  68. Guo J. Zhang Q.Y. Xu L. Li M. Sun Q.Y. Icariin ameliorates LPS-induced acute lung injury in mice via complement C5a-C5aR1 and TLR4 signaling pathways. Int. Immunopharmacol. 2024 131 111802 10.1016/j.intimp.2024.111802 38467082
    [Google Scholar]
  69. Gao S. Zhang X. Liu J. Icariin induces triple-negative breast cancer cell apoptosis and suppresses invasion by inhibiting the JNK/c-Jun signaling pathway. Drug Des. Devel. Ther. 2023 17 821 836 10.2147/DDDT.S398887 36969705
    [Google Scholar]
  70. Lee H.R. Yoo S.J. Kim J. Apurinic/apyrimidinic endonuclease 1 alleviates inflammation in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Cent. Eur. J. Immunol. 2024 49 2 113 125 10.5114/ceji.2024.141946 39381557
    [Google Scholar]
  71. Pang Y. Zhao L. Ji X. Guo K. Yin X. Analyses of transcriptomics upon IL-1β-stimulated mouse chondrocytes and the protective effect of catalpol through the NOD2/NF-κB/MAPK signaling pathway. Molecules 2023 28 4 1606 10.3390/molecules28041606 36838594
    [Google Scholar]
  72. Li W.W. Gao X.M. Wang X.M. Guo H. Zhang B.L. Icariin inhibits hydrogen peroxide-induced toxicity through inhibition of phosphorylation of JNK/p38 MAPK and p53 activity. Mutat. Res. 2011 708 1-2 1 10 10.1016/j.mrfmmm.2010.12.017 21236269
    [Google Scholar]
  73. Zhu T. Zhang F. Li H. Long-term icariin treatment ameliorates cognitive deficits via CD4+ T cell-mediated immuno-inflammatory responses in APP/PS1 mice. Clin. Interv. Aging 2019 14 817 826 10.2147/CIA.S208068 31190768
    [Google Scholar]
  74. Choi A.Y. Choi J.H. Lee J.Y. Apigenin protects HT22 murine hippocampal neuronal cells against endoplasmic reticulum stress-induced apoptosis. Neurochem. Int. 2010 57 2 143 152 10.1016/j.neuint.2010.05.006 20493918
    [Google Scholar]
  75. Chen L. Ou S. Zhou L. Tang H. Xu J. Guo K. Formononetin attenuates Aβ25-35-induced cytotoxicity in HT22 cells via PI3K/Akt signaling and non-amyloidogenic cleavage of APP. Neurosci. Lett. 2017 639 36 42 10.1016/j.neulet.2016.12.064 28034780
    [Google Scholar]
  76. Boraschi D. Italiani P. Migliorini P. Bossù P. Cause or consequence? The role of IL-1 family cytokines and receptors in neuroinflammatory and neurodegenerative diseases. Front. Immunol. 2023 14 1128190 10.3389/fimmu.2023.1128190 37223102
    [Google Scholar]
  77. Golan H. Levav T. Mendelsohn A. Huleihel M. Involvement of tumor necrosis factor alpha in hippocampal development and function. Cereb. Cortex 2004 14 1 97 105 10.1093/cercor/bhg108 14654461
    [Google Scholar]
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Multi-Method Investigation of Icariin's Effects on Diabetic Cognitive Impairment: From Network Prediction to Experimental Confirmation
Bentham Science Publishers ; https://doi.org/10.2174/0118715273406743250831224035
/content/journals/cnsnddt/10.2174/0118715273406743250831224035
/content/journals/cnsnddt/10.2174/0118715273406743250831224035
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  • Article Type:     Research Article
Keywords: MAPK pathway ; neuroinflammation ; diabetes ; diabetic cognitive impairment ; inflammation ; network pharmacology ; Icariin

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