The site of the Media Sphera Publishers contains materials intended solely for healthcare professionals.
By closing this message, you confirm that you are a certified medical professional or a student of a medical educational institution.

Berezutsky M.A.

Razumovsky Saratov State Medical University

Durnova N.A.

V.I. Razumovsky Saratov State Medical University;
I.M. Sechenov First Moscow State Medical University (Sechenov University)

Kurchatova M.N.

V.I. Razumovsky Saratov State Medical University

Matvienko U.A.

V.I. Razumovsky Saratov State Medical University

Neurobiological potential of astragaloside IV and prospects for its use in the treatment of Alzheimer’s disease

Authors:

Berezutsky M.A., Durnova N.A., Kurchatova M.N., Matvienko U.A.

More about the authors

Read: 1653 times


To cite this article:

Berezutsky MA, Durnova NA, Kurchatova MN, Matvienko UA. Neurobiological potential of astragaloside IV and prospects for its use in the treatment of Alzheimer’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;125(2):7‑12. (In Russ.)
https://doi.org/10.17116/jnevro20251250217

Recommended articles:
Como­rbidity of depression and deme­ntia: epidemiological, biological and therapeutic aspe­cts. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(11):113-121
Non-invasive biomarkers for early diagnosis of Alzheimer’s disease in bodily fluids. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(1):8-16
Cyto­kine status of patients with Alzheimer’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(4-2):5-12
Differential diagnosis of Alzheimer’s disease and vascular cognitive diso­rders. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(4-2):26-35
App-based first aid learning: what applications do we have now?. Russian Journal of Anesthesiology and Reanimatology. 2024;(6):89-103

References:

  1. Gavrilova SI, Kolykhalov IV, Kulik AS, et al. Clinical experience of the use of memantal in patients with moderate and severe Alzheimer’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2016;116(2):52-57. (In Russ.). https://doi.org/10.17116/jnevro20161162152-57
  2. Lane CA, Hardy J, Schott JM. Alzheimer’s disease. Eur J Neurol. 2018;25(1):59-70.  https://doi.org/10.1111/ene.13439
  3. Kovalenko EA, Makhnovich EV, Osinovskaya NA, et al. Focused ultrasound as a non-invasive method with therapeutic potential in patients with Alzheimer’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2022;122(10):38-45. (In Russ.). https://doi.org/10.17116/jnevro202212210138
  4. Sachan A, Singh S, Singh HK, et al. An experimental study to evaluate the effect of mucuna pruriens on learning and memory in mice. Int J Innov Sci Res. 2015;4(4):144-148. 
  5. Costa IM, Lima FO, Fernandes LC, et al. Astragaloside IV supplementation promotes a neuroprotective effect in experimental models of neurological disorders: a systematic review. Curr Neuropharmacol. 2019;17(7):648-665.  https://doi.org/10.2174/1570159X16666180911123341
  6. Yao J, Liu J, He Y, et al. Systems pharmacology reveals the mechanism of Astragaloside IV in improving immune activity on cyclophosphamide-induced immunosuppressed mice. J Ethnopharmacol. 2023;313:116533. https://doi.org/10.1016/j.jep.2023.116533
  7. Li L, Hou X, Xu R, et al. Research review on the pharmacological effects of astragaloside IV. Fundam Clin Pharmacol. 2017;31(1):17-36.  https://doi.org/10.1111/fcp.12232
  8. Zhou L, Li M, Chai Z, et al. Anticancer effects and mechanisms of astragaloside-IV. Oncol Rep. 2023;49(1):1-15.  https://doi.org/10.3892/or.2022.8442
  9. Berezutskii MA, Yakubova LR, Durnova NA, et al. Pharmacological properties of preparations based on Astragalus extract. Pharmaceutical Chemistry Journal. 2020;54(4):372-376.  https://doi.org/10.1007/s11094-020-02206-x
  10. Hsieh HL, Liu SH, Chen YL, et al. Astragaloside IV suppresses inflammatory response via suppression of NF-κB, and MAPK signalling in human bronchial epithelial cells. Arch Physiol Biochem. 2022;128(3):757-766.  https://doi.org/10.1080/13813455.2020.1727525
  11. Yuan F, Yang Y, Liu L, et al. Research progress on the mechanism of astragaloside IV in the treatment of asthma. Heliyon. 2023;9(11):e22149. https://doi.org/10.1016/j.heliyon.2023.e22149
  12. Qu C, Tan X, Hu Q, et al. A systematic review of astragaloside IV effects on animal models of diabetes mellitus and its complications. Heliyon. 2024;10(5):e26863. https://doi.org/10.1016/j.heliyon.2024.e26863
  13. Indu P, Arunagirinathan N, Rameshkumar MR, et al. Antiviral activity of astragaloside II, astragaloside III and astragaloside IV compounds against dengue virus: computational docking and in vitro studies. Microb Pathog. 2021;152:104563. https://doi.org/10.1016/j.micpath.2020.104563
  14. Berezutsky MA, Durnova NA, Vlasova IA. Experimental and clinical studies of mechanisms of the anti-aging effects of chemical compounds in Astragalus membranaceus (review). Advances in Gerontology= Uspekhi Gerontologii. 2019;32(5):702-710. 
  15. Stępnik K, Kukula-Koch W. In silico studies on triterpenoid saponins permeation through the blood–brain barrier combined with postmortem research on the brain tissues of mice affected by Astragaloside IV Administration. Int J Mol Sci. 2020;21(7):2534. https://doi.org/10.3390/ijms21072534
  16. Chen G, Ding H, Liu Y, et al. Study on phase I clinical tolerance of the astragalus a glycoside of glucose injection (Chin). Pharmacol. Clinics Chin Mat Medica. 2012;28:134-136. 
  17. Heppner FL, Ransohoff RM., Becher B. Immune attack: the role of inflammation in Alzheimer disease. Nat Rev Neurosci. 2015;16(6):358-372.  https://doi.org/10.1038/nrn3880
  18. Prokop S, Miller KR, Heppner FL. Microglia actions in Alzheimer’s disease. Acta Neuropathol. 2013;126(4):461-477.  https://doi.org/10.1007/s00401-013-1182-x
  19. Malashenkova IK, Hailov NA, Krynskiy SA, et al. Levels of proinflammatory cytokines and VEGF in patients with Alzheimer’s disease and mild cognitive impairment. S.S. Korsakov Journal of Neurology and Psychiatry. 2016;116(3):39-43. (In Russ.). https://doi.org/10.17116/jnevro20161163139-43
  20. He L, Sun J, Miao Z, et al. Astragaloside IV attenuates neuroinflammation and ameliorates cognitive impairment in Alzheimer’s disease via inhibiting NF-κB signaling pathway. Heliyon. 2023;9(2):e13411. https://doi.org/10.1016/j.heliyon.2023.e13411
  21. Liu HS, Shi HL, Huang F, et al. Astragaloside IV inhibits microglia activation via glucocorticoid receptor mediated signaling pathway. Sci Rep. 2016;6:19137. https://doi.org/10.1038/srep19137
  22. Li C, Yang F, Liu F, et al. NRF2/HO-1 activation via ERK pathway involved in the anti-neuroinflammatory effect of Astragaloside IV in LPS induced microglial cells. Neurosci Lett. 2018;666:104-110.  https://doi.org/10.1016/j.neulet.2017.12.039
  23. Yu J, Guo M, Li Y, et al. Astragaloside IV protects neurons from microglia-mediated cell damage through promoting microglia polarization. Folia Neuropathol. 2019;57(2):170-181.  https://doi.org/10.5114/fn.2019.86299
  24. Chen F, Yang D, Cheng XY, et al. Astragaloside IV ameliorates cognitive impairment and neuroinflammation in an oligomeric Aβ induced Alzheimer’s disease mouse model via inhibition of microglial activation and NADPH oxidase expression. Biol Pharm Bull. 2021;44(11):1688-1696. https://doi.org/10.1248/bpb.b21-00381
  25. Feng YS, Tan ZX, Wu LY, et al. The involvement of NLRP3 infammasome in the treatment of Alzheimer’s disease. Ageing Res Rev. 2020;64:101192. https://doi.org/10.1016/j.arr.2020.101192
  26. Song MT, Ruan J, Zhang RY, et al. Astragaloside IV ameliorates neuroinflammation-induced depressive-like behaviors in mice via the PPARγ/NF-κB/NLRP3 inflammasome axis. Acta Pharmacol Sin. 2018;39(10):1559-1570. https://doi.org/10.1038/aps.2017.208
  27. Huijbers W, Mormino EC, Schultz AP, et al. Amyloid-β Deposition in Mild Cognitive Impairment Is Associated with Increased Hippocampal Activity, Atrophy and Clinical Progression. Brain. 2015;138(Pt 4):1023-1035.
  28. Huijbers W, Schultz AP, Papp KV, et al. Tau Accumulation in Clinically Normal Older Adults Is Associated with Hippocampal Hyperactivity. J Neurosci. 2019;39(3):548-556.  https://doi.org/10.1523/JNEUROSCI.1397-18.2018
  29. Ghatak S, Dolatabadi N, Trudler D, et al. Mechanisms of hyperexcitability in Alzheimer’s disease hiPSC-derived neurons and cerebral organoids vs isogenic controls. Elife. 2019;8:e50333. https://doi.org/10.7554/eLife.50333
  30. Yue R, Li X, Chen B, et al. Astragaloside IV attenuates glutamate-induced neurotoxicity in PC12 cells through Raf-MEK-ERK pathway. PLoS One. 2015;10(5):e0126603. https://doi.org/10.1371/journal.pone.0126603
  31. Misrani A, Tabassum S, Yang L. Mitochondrial dysfunction and oxidative stress in Alzheimer’s disease. Front Aging Neurosci. 2021;13:617588. https://doi.org/10.3389/fnagi.2021.617588
  32. Llanos-Gonzalez E, Henares-Chavarino AA, Pedrero-Prieto CM, et al. Interplay Between Mitochondrial Oxidative Disorders and Proteostasis in Alzheimer’s Disease. Front Neurosci. 2020;13:1444. https://doi.org/10.3389/fnins.2019.01444
  33. Rak M, Benit P, Chretien D, et al. Mitochondrial cytochrome c oxidase deficiency. Clin Sci (Lond). 2016;130(6):393-407.  https://doi.org/10.1042/CS20150707
  34. Elgenaidi IS, Spiers JP. Regulation of the phosphoprotein phosphatase 2A system and its modulation during oxidative stress: A potential therapeutic target? Pharmacol Ther. 2019;198:68-89.  https://doi.org/10.1016/j.pharmthera.2019.02.011
  35. Toral-Rios D, Pichardo-Rojas PS, Alonso-Vanegas M, et al. GSK3β and Tau Protein in Alzheimer’s Disease and Epilepsy. Front Cell Neurosci. 2020;14:19.  https://doi.org/10.3389/fncel.2020.00019
  36. Liu Y, Chong E, Li X, et al. Astragaloside IV rescues MPP+-induced mitochondrial dysfunction through upregulation of methionine sulfoxide reductase A. Exp Ther Med. 2017;14(3):2650-2656. https://doi.org/10.3892/etm.2017.4834
  37. Ben Y, Hao J, Zhang Z, et al. Astragaloside IV inhibits mitochondrial-dependent apoptosis of the dorsal root ganglion in diabetic peripheral neuropathy rats through modulation of the SIRT1/p53 signaling pathway. Diabetes Metab Syndr Obes. 2021;14:1647-1661. https://doi.org/10.2147/DMSO.S301068
  38. Sun Q, Jia N, Wang W, et al. Protective effects of astragaloside IV against amyloid beta1-42 neurotoxicity by inhibiting the mitochondrial permeability transition pore opening. PloS One. 2014;9(6):e98866. https://doi.org/10.1371/journal.pone.0098866
  39. Qu M, Zhou Z, Chen C, et al. Inhibition of mitochondrial permeability transition pore opening is involved in the protective effects of mortalin overexpression against beta-amyloid-induced apoptosis in SH-SY5Y cells. Neurosci Res. 2012;72(1):94-102.  https://doi.org/10.1016/j.neures.2011.09.009
  40. Chen W, Chan Y, Wan W, et al. Aβ1-42 induces cell damage via RAGE-dependent endoplasmic reticulum stress in bEnd.3 cells. Exp Cell Res. 2018;362(1):83-89.  https://doi.org/10.1016/j.yexcr.2017.11.005
  41. Ma Y, Xiong L. Astragaloside IV ameliorates endoplasmic reticulum stress-induced apoptosis of Aβ25-35-treated PC12 cells by inhibiting the p38 MAPK signaling pathway. Mol Med Rep. 2019;19(3):2005-2012. https://doi.org/10.3892/mmr.2019.9855
  42. Gao ML, Zhang YD, Li N, et al. Bone marrow mesenchymal stem cells transplanted into a rat model of Alzheimer’s disease: improvement in the learning and memory ability. Zhongguo Zuzhi Gongcheng Yanjiu. 2016;20:2059-2065.
  43. Sultana R, Banks WA, Butterfield DA. Decreased levels of PSD95 and two associated proteins and increased levels of BCl2 and caspase 3 in hippocampus from subjects with amnestic mild cognitive impairment: Insights into their potential roles for loss of synapses and memory, accumulation of Abeta, and neurodegeneration in a prodromal stage of Alzheimer’s disease. J Neurosci Res. 2010;88(3):469-477.  https://doi.org/10.1002/jnr.22227
  44. Wang X, Gao F, Xu W, et al. Depichering the effects of astragaloside IV on AD‐like phenotypes: a systematic and experimental investigation. Oxid Med Cell Longev. 2021;2021:1020614. https://doi.org/10.1155/2021/1020614
  45. Schliebs R, Arendt T. The significance of the cholinergic system in the brain during aging and in Alzheimer’s disease. J Neural Transm (Vienna). 2006;113(11):1625-1644. https://doi.org/10.1007/s00702-006-0579-2
  46. Colović MB, Krstić DZ, Lazarević-Pašti TD, et al. Acetylcholinesterase inhibitors: Pharmacology and toxicology. Curr Neuropharmacol. 2013;11(3):315-335.  https://doi.org/10.2174/1570159X11311030006
  47. Chang Y, Bai M, Zhang X, et al. Neuroprotective and acetylcholinesterase inhibitory activities of alkaloids from Solanum lyratum Thunb.: An in vitro and in silico analyses. Phytochemistry. 2023;209:113623. https://doi.org/10.1016/j.phytochem.2023.113623
  48. Stępnik K, Kukula-Koch W, Plazinski W, et al. Significance of astragaloside IV from the roots of Astragalus mongholicus as an acetylcholinesterase inhibitor—From the computational and biomimetic analyses to the in vitro and in vivo studies of safety. Int J Mol Sci. 2023;24(11):9152. https://doi.org/10.3390/ijms24119152
  49. Govindarajulu M, Pinky PD, Bloemer J, et al. Signaling mechanisms of selective PPARγ modulators in Alzheimer’s disease. PPAR Res. 2018;2018:2010675. https://doi.org/10.1155/2018/2010675
  50. Michailidis M, Moraitou D, Tata DA, et al. Alzheimer’s disease as type 3 diabetes: common pathophysiological mechanisms between Alzheimer’s disease and type 2 diabetes. Int J Mol Sci. 2022;23(5):2687. https://doi.org/10.3390/ijms23052687
  51. Landreth G, Jiang Q, Mandrekar S, et al. PPARγ agonists as therapeutics for the treatment of Alzheimer’s disease. Neurotherapeutics. 2008;5(3):481-489. 
  52. Wang X, Wang Y, Hu JP, et al. Astragaloside IV, a natural PPARγ agonist, reduces Aβ production in Alzheimer’s disease through inhibition of BACE1. Mol Neurobiol. 2017;54(4):2939-2949. https://doi.org/10.1007/s12035-016-9874-6
  53. Wang X, Xu W, Chen H, et al. Astragaloside IV prevents Aβ1-42 oligomers-induced memory impairment and hippocampal cell apoptosis by promoting PPARγ/BDNF signaling pathway. Brain Res. 2020;1747:147041. https://doi.org/10.1016/j.brainres.2020.147041
  54. Rodríguez JJ, Jones VC, Tabuchi M, et al. Impaired adult neurogenesis in the dentate gyrus of a triple transgenic mouse model of Alzheimer’s Ddisease. PLoS ONE. 2008;3(8):e2935. https://doi.org/10.1371/journal.pone.0002935
  55. Jin K, Peel AL, Mao XO, et al. Increased hippocampal neurogenesis in Alzheimer’s disease. Proc Natl Acad Sci U S A. 2004;101(1):343-347.  https://doi.org/10.1073/pnas.2634794100
  56. Haiyan H, Rensong Y, Guoqin J, et al. Effect of astragaloside IV on neural stem cell transplantation in Alzheimer’s disease rat models. Evid Based Complement Alternat Med. 2016;2016:3106980. https://doi.org/10.1155/2016/3106980
  57. Yin Y, Yan L, Huang LQ, et al. Anti-apoptosis effect of astragaloside IV on Alzheimer’s disease rat model via enhancing the expression of Bcl-2 and Bcl-xl. Scand J Lab Anim Sci. 2010;37(2):75-82.  https://doi.org/10.23675/sjlas.v37i2.206
  58. Yu C, Zhang J, Li X, et al. Astragaloside IV-induced Nrf2 nuclear translocation ameliorates lead-related cognitive impairments in mice. Biochim Biophys Acta Mol Cell Res. 2021;1868(1):118853. https://doi.org/10.1016/j.bbamcr.2020.118853

Email Confirmation

An email was sent to test@gmail.com with a confirmation link. Follow the link from the letter to complete the registration on the site.

Email Confirmation

We use cооkies to improve the performance of the site. By staying on our site, you agree to the terms of use of cооkies. To view our Privacy and Cookie Policy, please. click here.