Skip to content
2000
image of Anti-Alzheimer's Disease Target and Beneficial Effect in Formononetin

Abstract

Introduction

Alzheimer's Disease (AD), a common neurodegenerative relevance of dementia, is spreading in the world. Hitherto, the pharmacological treatment for AD is prescribed limitedly in clinical application. Recently, it has been found that naturally occurring extracts possess promising anti-neurodegenerative properties, including AD.

Method

Our previous study indicated that formononetin (FMN) exerts the anti-AD benefits based on bioinformatics analysis. However, the experimental validation for bioinformatics findings has not been conducted. In this study, we primarily applied the molecule docking analysis to ascertain the pharmacological targets, including cytochrome P450 19A1 (CYP19A1). Transgenic AD mice were used to validate the bioinformatics findings experimentally. Molecular docking data showed that FMN acted directly on CYP19A1 target protein with effective binding sites and potent combining affinity/energy.

Results

Meanwhile, FMN intervention contributed to an increased trend of body weight in transgenic AD mice reduced hippocampal expression of Aβ1-42, and elevated content of CYP19A1. Additionally, FMN intervention showed reduced terminal deoxynucleotidyl Transferase dUTP Nick-End Labeling (TUNEL) expression and increased CYP19A1 and Ki67 expressions in hippocampal sections of transgenic AD mice.

Conclusion

Collectively, FMN may be used for the prevention of AD, and the pharmacological activities are possibly related to reducing Aβ1-42, and TUNEL expressions to increase Ki67 and CYP19A1 activities.

Loading

Article metrics loading...

/content/journals/cnf/10.2174/0115734013305275241022104452
2024-11-01
2024-11-26
Loading full text...

Full text loading...

References

  1. Soria Lopez J.A. González H.M. Léger G.C. Alzheimer’s disease. Handb. Clin. Neurol. 2019 167 231 255 10.1016/B978‑0‑12‑804766‑8.00013‑3 31753135
    [Google Scholar]
  2. 2023 Alzheimer’s disease facts and figures. Alzheimers Dement. 2023 19 4 1598 1695 10.1002/alz.13016 36918389
    [Google Scholar]
  3. Wang Q. Gao F. Dai L.N. Zhang J. Bi D. Shen Y. Clinical research investigating alzheimer’s disease in China: Current status and future perspectives toward prevention. J. Prev. Alzheimers Dis. 2022 9 3 532 541 35841254
    [Google Scholar]
  4. Rostagno A.A. Pathogenesis of alzheimer’s disease. Int. J. Mol. Sci. 2022 24 1 107 10.3390/ijms24010107 36613544
    [Google Scholar]
  5. Briggs R. Kennelly S.P. O’Neill D. Drug treatments in alzheimer’s disease. Clin. Med. 2016 16 3 247 253 10.7861/clinmedicine.16‑3‑247 27251914
    [Google Scholar]
  6. Pei H. Ma L. Cao Y. Wang F. Li Z. Liu N. Liu M. Wei Y. Li H. Traditional Chinese medicine for alzheimer’s disease and other cognitive impairment: A review. Am. J. Chin. Med. 2020 48 3 487 511 10.1142/S0192415X20500251 32329645
    [Google Scholar]
  7. Ding M.R. Qu Y.J. Hu B. An H.M. Signal pathways in the treatment of Alzheimer’s disease with traditional Chinese medicine. Biomed. Pharmacother. 2022 152 113208 10.1016/j.biopha.2022.113208 35660246
    [Google Scholar]
  8. Machado Dutra J. Espitia P.J.P. Andrade Batista R. Formononetin: Biological effects and uses – A review. Food Chem. 2021 359 129975 10.1016/j.foodchem.2021.129975 33962193
    [Google Scholar]
  9. Ding M. Bao Y. Liang H. Zhang X. Li B. Yang R. Zeng N. Potential mechanisms of formononetin against inflammation and oxidative stress: A review. Front. Pharmacol. 2024 15 1368765 10.3389/fphar.2024.1368765 38799172
    [Google Scholar]
  10. Ma X. Wang J. Formononetin: A pathway to protect neurons. Front. Integr. Nuerosci. 2022 16 908378 10.3389/fnint.2022.908378 35910340
    [Google Scholar]
  11. Singh L. Kaur H. Chandra Arya G. Bhatti R. Neuroprotective potential of formononetin, a naturally occurring isoflavone phytoestrogen. Chem. Biol. Drug Des. 2024 103 1 e14353 10.1111/cbdd.14353 37722967
    [Google Scholar]
  12. Tian J. Wang X.Q. Tian Z. Focusing on formononetin: Recent perspectives for its neuroprotective potentials. Front. Pharmacol. 2022 13 905898 10.3389/fphar.2022.905898 35712702
    [Google Scholar]
  13. Xiao H. Qin X. Wan J. Li R. Pharmacological targets and the biological mechanisms of formononetin for alzheimer’s disease: A network analysis. Med. Sci. Monit. 2019 25 4273 4277 10.12659/MSM.916662 31175839
    [Google Scholar]
  14. Saikia S. Bordoloi M. Molecular docking: Challenges, advances and its use in drug discovery perspective. Curr. Drug Targets 2019 20 5 501 521 10.2174/1389450119666181022153016 30360733
    [Google Scholar]
  15. Bitam S. Hamadache M. Hanini S. Targeting bladder cancer with Trigonella foenum-graecum: A computational study using network pharmacology and molecular docking. J. Biomol. Struct. Dyn. 2024 42 6 3286 3293 10.1080/07391102.2023.2217926 37232424
    [Google Scholar]
  16. Fei H.X. Zhang Y.B. Liu T. Zhang X.J. Wu S.L. Neuroprotective effect of formononetin in ameliorating learning and memory impairment in mouse model of Alzheimer’s disease. Biosci. Biotechnol. Biochem. 2018 82 1 57 64 10.1080/09168451.2017.1399788 29191087
    [Google Scholar]
  17. Ashrafian H. Zadeh E.H. Khan R.H. Review on Alzheimer’s disease: Inhibition of amyloid beta and tau tangle formation. Int. J. Biol. Macromol. 2021 167 382 394 10.1016/j.ijbiomac.2020.11.192 33278431
    [Google Scholar]
  18. Pinheiro L. Faustino C. Therapeutic strategies targeting amyloid-β in alzheimer’s disease. Curr. Alzheimer Res. 2019 16 5 418 452 10.2174/1567205016666190321163438 30907320
    [Google Scholar]
  19. Butterfield D.A. Swomley A.M. Sultana R. Amyloid β-peptide (1-42)-induced oxidative stress in Alzheimer disease: importance in disease pathogenesis and progression. Antioxid. Redox Signal. 2013 19 8 823 835 10.1089/ars.2012.5027 23249141
    [Google Scholar]
  20. Leong Y.Q. Ng K.Y. Chye S.M. Ling A.P.K. Koh R.Y. Mechanisms of action of amyloid-beta and its precursor protein in neuronal cell death. Metab. Brain Dis. 2020 35 1 11 30 10.1007/s11011‑019‑00516‑y 31811496
    [Google Scholar]
  21. Kam M.K. Kim B. Lee D.G. Lee H.J. Park Y.H. Lee D.S. Amyloid beta oligomers-induced parkin aggravates ER stress-mediated cell death through a positive feedback loop. Neurochem. Int. 2022 155 105312 10.1016/j.neuint.2022.105312 35231558
    [Google Scholar]
  22. Kyrylkova K. Kyryachenko S. Leid M. Kioussi C. Detection of apoptosis by TUNEL assay. Methods Mol. Biol. 2012 887 41 47 10.1007/978‑1‑61779‑860‑3_5 22566045
    [Google Scholar]
  23. Mirzayans R. Murray D. Do TUNEL and other apoptosis assays detect cell death in preclinical studies? Int. J. Mol. Sci. 2020 21 23 9090 10.3390/ijms21239090 33260475
    [Google Scholar]
  24. Graefe C. Eichhorn L. Wurst P. Kleiner J. Heine A. Panetas I. Abdulla Z. Hoeft A. Frede S. Kurts C. Endl E. Weisheit C.K. Optimized Ki-67 staining in murine cells: A tool to determine cell proliferation. Mol. Biol. Rep. 2019 46 4 4631 4643 10.1007/s11033‑019‑04851‑2 31093875
    [Google Scholar]
  25. Murata Y. Jo J.I. Tabata Y. Molecular beacon imaging to visualize ki67 mrna for cell proliferation ability. Tissue Eng. Part A 2021 27 9-10 526 535 10.1089/ten.tea.2020.0127 32723028
    [Google Scholar]
  26. Parween S. DiNardo G. Baj F. Zhang C. Gilardi G. Pandey A.V. Differential effects of variations in human P450 oxidoreductase on the aromatase activity of CYP19A1 polymorphisms R264C and R264H. J. Steroid Biochem. Mol. Biol. 2020 196 105507 10.1016/j.jsbmb.2019.105507 31669572
    [Google Scholar]
  27. Lu X. Duan A. Ma X. Liang S. Deng T. Knockdown of CYP19A1 in buffalo follicular granulosa cells results in increased progesterone secretion and promotes cell proliferation. Front. Vet. Sci. 2020 7 539496 10.3389/fvets.2020.539496 33102564
    [Google Scholar]
  28. Li Q. Du X. Liu L. Liu H. Pan Z. Li Q. Upregulation of miR-146b promotes porcine ovarian granulosa cell apoptosis by attenuating CYP19A1. Domest. Anim. Endocrinol. 2021 74 106509 10.1016/j.domaniend.2020.106509 32653739
    [Google Scholar]
/content/journals/cnf/10.2174/0115734013305275241022104452
Loading
/content/journals/cnf/10.2174/0115734013305275241022104452
Loading

Data & Media loading...


  • Article Type:
    Research Article
Keywords: biomarker ; Alzheimer's disease ; cell growth ; pharmacological activity ; Formononetin
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