Folia Biologica
Journal of Cellular and Molecular Biology, Charles University 

Crossref logo

Fol. Biol. 2025, 71, 140-148

https://doi.org/10.14712/fb2025071030140

Atractylenolide III Promotes Astrocyte Aβ Clearance by Up-regulating AQP4 to Improve Alzheimer’s Disease

Jingwen HaoID, Qi Wan, Chanjuan ChenID

Department of Neurology, the First Hospital of Changsha City, Changsha, Hunan, China

Received December 6, 2024
Accepted August 8, 2025

References

1. Assefa, B. T., Gebre, A. K., Altaye, B. M. (2018) Reactive astrocytes as drug target in Alzheimer’s disease. Biomed Res. Int. 2018, 4160247. <https://doi.org/10.1155/2018/4160247>
2. Assis-Nascimento, P., Jarvis, K. M., Montague, J. R. et al. (2007) Beta-amyloid toxicity in embryonic rat astrocytes. Neurochem. Res. 32, 1476-1482. <https://doi.org/10.1007/s11064-007-9335-8>
3. Butterfield, D. A., Boyd-Kimball, D. (2004) Amyloid β-pep­tide(1–42) contributes to the oxidative stress and neurodegeneration found in Alzheimer disease brain. Brain Pathol. 14, 426-432. <https://doi.org/10.1111/j.1750-3639.2004.tb00087.x>
4. Chenxing, W., Jie, S., Yajuan, T. et al. (2024) The rhizomes of Atractylodes macrocephala Koidz improve gastrointestinal health and pregnancy outcomes in pregnant mice via mo­dulating intestinal barrier and water-fluid metabolism. J. Ethno­pharmacol. 326, 117971. <https://doi.org/10.1016/j.jep.2024.117971>
5. Choi, S. S., Lee, H. J., Lim, I. et al. (2014) Human astrocytes: secretome profiles of cytokines and chemokines. PLoS One 9, e92325. <https://doi.org/10.1371/journal.pone.0092325>
6. Choi, S. S., Lee, S. R., Lee, H. J. (2016) Neurorestorative role of stem cells in Alzheimer’s disease: astrocyte involvement. Curr. Alzheimer Res. 13, 419-427. <https://doi.org/10.2174/156720501304160314162812>
7. Chung, W. S., Clarke, L. E., Wang, G. X. et al. (2013) Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways. Nature 504, 394-400. <https://doi.org/10.1038/nature12776>
8. Dal Prà, I., Chiarini, A., Pacchiana, R. et al. (2014) Calcium-sensing receptors of human astrocyte-neuron teams: amy­loid-β-driven mediators and therapeutic targets of Alzhei­mer’s disease. Curr. Neuropharmacol. 12, 353-364.
9. Feng, S., Wu, C., Zou, P. et al. (2023) High-intensity interval training ameliorates Alzheimer’s disease-like pathology by regulating astrocyte phenotype-associated AQP4 polarization. Theranostics 13, 3434-3450. <https://doi.org/10.7150/thno.81951>
10. Feng, W., Zhang, Y., Wang, Z. et al. (2020) Microglia prevent beta-amyloid plaque formation in the early stage of an Alzheimer’s disease mouse model with suppression of glymphatic clearance. Alzheimers Res. Ther. 12, 125. <https://doi.org/10.1186/s13195-020-00688-1>
11. Forny-Germano, L., Lyra e Silva, N. M., Batista, A. F. et al. (2014) Alzheimer’s disease-like pathology induced by amyloid-β oligomers in nonhuman primates. J. Neurosci. 34, 13629-13643. <https://doi.org/10.1523/JNEUROSCI.1353-14.2014>
12. Huang, Y., Mucke, L. (2012) Alzheimer mechanisms and therapeutic strategies. Cell 148, 1204-1222. <https://doi.org/10.1016/j.cell.2012.02.040>
13. Iliff, J. J., Wang, M., Liao, Y. et al. (2012) A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci. Transl. Med. 4, 147ra111. <https://doi.org/10.1126/scitranslmed.3003748>
14. Jeong, Y. H., Li, W., Go, Y. et al. (2019) 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. 20, 4015. <https://doi.org/10.3390/ijms20164015>
15. Ji, G. Q., Chen, R. Q.,Wang, L. (2016) Anti-inflammatory activity of atractylenolide III through inhibition of nuclear factor-κB and mitogen-activated protein kinase pathways in mouse macrophages. Immunopharmacol. Immunotoxicol. 38, 98-102. <https://doi.org/10.3109/08923973.2015.1122617>
16. Kim, S., Chun, H., Kim, Y. et al. (2024) Astrocytic autophagy plasticity modulates Aβ clearance and cognitive function in Alzheimer’s disease. Mol. Neurodegener. 19, 55. <https://doi.org/10.1186/s13024-024-00740-w>
17. Lemus Silva, E. G., Delgadillo, Y., White, R. E. et al. (2023) Beclin 1 regulates astrocyte phagocytosis and phagosomal recruitment of retromer. Tissue Cell 82, 102100. <https://doi.org/10.1016/j.tice.2023.102100>
18. Li, C., Zhao, R., Gao, K. et al. (2011) Astrocytes: implications for neuroinflammatory pathogenesis of Alzheimer’s disease. Curr. Alzheimer Res. 8, 67-80. <https://doi.org/10.2174/156720511794604543>
19. Liu, G., Xie, R., Tan, Q. et al. (2024) Pharmacokinetic study and neuropharmacological effects of atractylenolide Ⅲ to improve cognitive impairment via PI3K/AKT/GSK3β pathway in intracerebroventricular-streptozotocin rats. J. Ethnopharmacol. 333, 118420. <https://doi.org/10.1016/j.jep.2024.118420>
20. Luo, Y., Wang, Q., Zhang, Y. (2016) A systems pharmacology approach to decipher the mechanism of danggui-shaoyao-san decoction for the treatment of neurodegenerative diseases. J. Ethnopharmacol. 178, 66-81. <https://doi.org/10.1016/j.jep.2015.12.011>
21. Maresca, B., Spagnuolo, M. S., Cigliano, L. (2015) Haptoglobin modulates beta-amyloid uptake by U-87 MG astrocyte cell line. J. Mol. Neurosci. 56, 35-47. <https://doi.org/10.1007/s12031-014-0465-6>
22. Min, L. J., Kobayashi, Y., Mogi, M. et al. (2017) Administration of bovine casein-derived peptide prevents cognitive decline in Alzheimer disease model mice. PLoS One 12, e0171515. <https://doi.org/10.1371/journal.pone.0171515>
23. Mulder, S. D., Veerhuis, R., Blankenstein, M. A. et al. (2012) The effect of amyloid associated proteins on the expression of genes involved in amyloid-β clearance by adult human astrocytes. Exp. Neurol. 233, 373-379. <https://doi.org/10.1016/j.expneurol.2011.11.001>
24. Nagelhus, E. A., Ottersen, O. P. (2013) Physiological roles of aquaporin-4 in brain. Physiol. Rev. 93, 1543-1562. <https://doi.org/10.1152/physrev.00011.2013>
25. Pedersen, T. J., Keil, S. A., Han, W. et al. (2023) The effect of aquaporin-4 mis-localization on Aβ deposition in mice. Neurobiol. Dis. 181, 106100. <https://doi.org/10.1016/j.nbd.2023.106100>
26. Peng, W., Achariyar, T. M., Li, B. et al. (2016) Suppression of glymphatic fluid transport in a mouse model of Alzheimer’s disease. Neurobiol. Dis. 93, 215-225. <https://doi.org/10.1016/j.nbd.2016.05.015>
27. Rosu, G. C., Catalin, B., Balseanu, T. A. et al. (2020) Inhibition of aquaporin 4 decreases amyloid Aβ40 drainage around cerebral vessels. Mol. Neurobiol. 57, 4720-4734. <https://doi.org/10.1007/s12035-020-02044-8>
28. Scheltens, P., De Strooper, B., Kivipelto, M. et al. (2021) Alzheimer’s disease. Lancet 397, 1577-1590. <https://doi.org/10.1016/S0140-6736(20)32205-4>
29. Simon, M., Wang, M. X., Ismail, O. et al. (2022) Loss of perivascular aquaporin-4 localization impairs glymphatic exchange and promotes amyloid β plaque formation in mice. Alzheimers Res. Ther. 14, 59. <https://doi.org/10.1186/s13195-022-00999-5>
30. Tarasoff-Conway, J. M., Carare, R. O., Osorio, R. S. et al. (2015) Clearance systems in the brain - implications for Alzheimer disease. Nat. Rev. Neurol. 11, 457-470. <https://doi.org/10.1038/nrneurol.2015.119>
31. Thal, D. R. (2012) The role of astrocytes in amyloid β-protein toxicity and clearance. Exp. Neurol. 236, 1-5. <https://doi.org/10.1016/j.expneurol.2012.04.021>
32. van Kralingen, C., Kho, D. T., Costa, J. et al. (2013) Exposure to inflammatory cytokines IL-1β and TNFα induces compromise and death of astrocytes; implications for chronic neuroinflammation. PLoS One 8, e84269. <https://doi.org/10.1371/journal.pone.0084269>
33. Wang, K. T., Chen, L. G., Wu, C. H. et al. (2010) Gastroprotective activity of atractylenolide III from Atractylodes ovata on ethanol-induced gastric ulcer in vitro and in vivo. J. Pharm. Pharmacol. 62, 381-388. <https://doi.org/10.1211/jpp.62.03.0014>
34. Wei, Z., Chen, X.-C., Song, Y. et al. (2016) Amyloid β protein aggravates neuronal senescence and cognitive deficits in 5XFAD mouse model of Alzheimer’s disease. Chin. Med. J. (Engl.) 129, 1835-1844. <https://doi.org/10.4103/0366-6999.186646>
35. Xie, L., Jiang, C., Wang, Z. et al. (2016) Effect of Huperzine A on Aβ-induced p65 of astrocyte in vitro. Biosci. Biotechnol. Biochem. 80, 2334-2337. <https://doi.org/10.1080/09168451.2016.1222265>
36. Xu, Z., Xiao, N., Chen, Y. et al. (2015) Deletion of aquaporin-4 in APP/PS1 mice exacerbates brain Aβ accumulation and memory deficits. Mol. Neurodegener. 10, 58. <https://doi.org/10.1186/s13024-015-0056-1>
37. Yang, W., Wu, Q., Yuan, C. et al. (2012) Aquaporin-4 mediates astrocyte response to β-amyloid. Mol. Cell. Neurosci. 49, 406-414. <https://doi.org/10.1016/j.mcn.2012.02.002>
38. Zhang, F., Cao, R. L., Liu, P. et al. (2023) The bexarotene derivative OAB-14 ameliorates cognitive decline in APP/PS1 transgenic mice by suppressing microglia-mediated neuroinflammation through the PPAR-γ pathway. Int. Immunopharmacol. 124, 110911. <https://doi.org/10.1016/j.intimp.2023.110911>
39. Zhao, H., Ji, Z. H., Liu, C., et al. (2015) Neuroprotection and mechanisms of atractylenolide III in preventing learning and memory impairment induced by chronic high-dose homo­cysteine administration in rats. Neuroscience 290, 485-491. <https://doi.org/10.1016/j.neuroscience.2015.01.060>
40. Zhao, X., Sun, J., Xiong, L. et al. (2023) β-amyloid binds to microglia Dectin-1 to induce inflammatory response in the pathogenesis of Alzheimer’s disease. Int. J. Biol. Sci. 19, 3249-3265. <https://doi.org/10.7150/ijbs.81900>
41. Zhu, B., Zhang, Q. L., Hua, J. W. et al. (2018) The traditional uses, phytochemistry, and pharmacology of Atractylodes macrocephala Koidz.: a review. J. Ethnopharmacol. 226, 143-167. <https://doi.org/10.1016/j.jep.2018.08.023>
front cover

ISSN 0015-5500 (Print) ISSN 2533-7602 (Online)

Open access journal

Submissions

Archive