Nano-magnolol enhances the modulatory effects of magnolol on cognitive performance and BACE1-related biochemical changes in an STZ-induced rat model of Alzheimer’s disease
Source abstract
Abstract
Abstract Background The Late-onset Alzheimer’s disease (LOAD) is progressive cognitive deficits associated with different abnormalities as cholinergic dysfunction, amyloid accumulation, inflammation, and oxidative stress. Magnolol is a polyphenolic compound that abrogated the neurodegenerative disease. The application of nanoparticles in medicine showed high bioavailability and low side effects for development of novel effective therapies. This study evaluated the neuroprotective potential of magnolol nanoparticles against streptozotocin (STZ) injected in intracerebroventricularly (ICV) induced Alzheimer’s disease (AD) in rats. Methods In current study, six groups of male Wister rats (10 rats/ group) were injected with STZ (2 mg/kg) in ICV bilaterally for induction of pathological features similar to AD. Rats were then treated with either magnolol or nano-magnolol or donepezil ( p.o ). Behavioral analysis was evaluated as the Morris Water Maze (MWM), Y-Maze, Novel Object Recognition (NOR), Passive Avoidance (PA), Elevated plus Maze (EPM), and Open Field Test (OFT). In addition, biochemical markers including brain acetylcholinesterase (AChE), glutathione-S-transferase (GST), B-secretase1 (BACE1) activities and nuclear factor kappa-B (NF-κB) were analyzed in hippocampal tissue. Results Data obtained showed that nano-magnolol significantly showed a neuroprotective effect in LOAD rat model by restoring GST activity and effectively decreased the activities of AChE, BACE1 and level of NF-κB compared to both donepezil and magnolol. Molecular docking studies indicated strengthen the affinity of magnolol to the BACE-1 active site. Conclusion Nano-magnolol is promising in developing a new agent targeting cholinergic function, amyloidogenesis, neuro-inflammation, and oxidative stress reflecting its potent neuroprotective efficacy in AD treatment.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Magnolia and Illicium research · Nuclear Receptors and Signaling · Alkaloids: synthesis and pharmacology
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (87)
Show source-provided references
1. Abdallah HM, El Sayed NS, Sirwi A, Ibrahim SR, Mohamed GA, Abdel Rasheed NO. Mangostanaxanthone IV ameliorates streptozotocin-induced neuro-inflammation, amyloid deposition, and tau hyperphosphorylation via modulating PI3K/Akt/GSK-3β pathway. Biology Basel. 2021;10(12):1298.10.3390/biology10121298 ↗
2. Akhtar A, Dhaliwal J, Saroj P, Uniyal A, Bishnoi M, Sah SP. Chromium picolinate attenuates cognitive deficit in ICV-STZ rat paradigm of sporadic Alzheimer’s-like dementia via targeting neuroinflammatory and IRS-1/PI3K/AKT/GSK-3β pathway. Inflammopharmacology. 2020;28(2):385–400. https://doi.org/10.1007/s10787-019-00681-7.10.1007/s10787-019-00681-7 ↗
3. Almahozi A, Radhi M, Alzayer S, Kamal A. Effects of Memantine in a mouse model of postoperative cognitive dysfunction. Behav Sci. 2019;9(3):Article 3. https://doi.org/10.3390/bs9030024.10.3390/bs9030024 ↗
4. Altinoglu G, Adali T. Alzheimer’s disease targeted nano-based drug delivery systems. Curr Drug Targets. 2020;21(7):628–46.10.2174/1389450120666191118123151 ↗
5. Arabian M, Aboutaleb N, Soleimani M, Ajami M, Habibey R, Rezaei Y, et al. Preconditioning with morphine protects hippocampal CA1 neurons from ischemia–reperfusion injury via activation of the mTOR pathway. Can J Physiol Pharmacol. 2018;96(1):80–7. https://doi.org/10.1139/cjpp-2017-0245.10.1139/cjpp-2017-0245 ↗
6. Bi D, Bao H, Yang X, Wu Z, Yang X, Xu G, et al. BACE1-dependent cleavage of GABAA receptor contributes to neural hyperexcitability and disease progression in Alzheimer’s disease. Neuron. 2025;113(7):1051-1064.e6. https://doi.org/10.1016/j.neuron.2025.01.030.10.1016/j.neuron.2025.01.030 ↗
7. Breijyeh Z, Karaman R. Comprehensive review on Alzheimer’s disease: causes and treatment. Molecules. 2020;25(24):5789. https://doi.org/10.3390/molecules25245789.10.3390/molecules25245789 ↗
8. Buccellato FR, D’Anca M, Tartaglia GM, Del Fabbro M, Scarpini E, Galimberti D. Treatment of Alzheimer’s disease: beyond symptomatic therapies. Int J Mol Sci. 2023;24(18):Article 18. https://doi.org/10.3390/ijms241813900.10.3390/ijms241813900 ↗
9. Cavaleri F. Reevaluating the role of amyloid β-peptides in Alzheimer’s disease: from pathogenic agents to protective chelation mechanisms. Front Neurol. 2025;16:1550709. https://doi.org/10.3389/fneur.2025.1550709.10.3389/fneur.2025.1550709 ↗
10. Calderón-Garcidueñas L, Hernández-Luna J, Aiello-Mora M, Brito-Aguilar R, Evelson PA, Villarreal-Ríos R, et al. APOE peripheral and brain impact: APOE4 carriers accelerate their Alzheimer continuum and have a high risk of suicide in PM2.5 polluted cities. Biomolecules. 2023;13(6):927. https://doi.org/10.3390/biom13060927.10.3390/biom13060927 ↗
11. Canady VA. FDA approves new treatment for Alzheimer’s disease. Ment Health Wkly. 2023;33(3):6–7. https://doi.org/10.1002/mhw.33505.10.1002/mhw.33505 ↗
12. Chaudhary S, Zhornitsky S, Chao HH, van Dyck CH, Li C-SR. Emotion processing dysfunction in Alzheimer’s disease: an overview of behavioral findings, systems neural correlates, and underlying neural biology. Am J Alzheimer’s Dis Other Dementias®. 2022;37:15333175221082834. https://doi.org/10.1177/15333175221082834.10.1177/15333175221082834 ↗
13. Chen H, Fu W, Chen H, You S, Liu X, Yang Y, et al. Magnolol attenuates the inflammation and enhances phagocytosis through the activation of MAPK, NF-κB signal pathways in vitro and in vivo. Mol Immunol. 2019;105:96–106.10.1016/j.molimm.2018.11.008 ↗
14. Chen Q, Riviere JE, Lin Z. Toxicokinetics, dose–response, and risk assessment of nanomaterials: methodology, challenges, and future perspectives. WIREs Nanomed Nanobiotechnol. 2022;14(6):e1808. https://doi.org/10.1002/wnan.1808.10.1002/wnan.1808 ↗
15. Cheng J, Dong S, Yi L, Geng D, Liu Q. Magnolol abrogates chronic mild stress-induced depressive-like behaviors by inhibiting neuroinflammation and oxidative stress in the prefrontal cortex of mice. Int Immunopharmacol. 2018;59:61–7.10.1016/j.intimp.2018.03.031 ↗
16. Chiapinotto Spiazzi C, Bucco Soares M, Pinto Izaguirry A, Musacchio Vargas L, Zanchi MM, Frasson Pavin N, et al. Selenofuranoside ameliorates memory loss in Alzheimer-like sporadic dementia: AChE activity, oxidative stress, and inflammation involvement. Oxid Med Cell Longev. 2015;2015(1):976908. https://doi.org/10.1155/2015/976908.10.1155/2015/976908 ↗
17. Chu J, Yang R, Cheng W, Cui L, Pan H, Liu J, et al. Semisynthesis, biological activities, and mechanism studies of Mannich base analogues of magnolol/honokiol as potential α-glucosidase inhibitors. Bioorg Med Chem. 2022;75:117070.10.1016/j.bmc.2022.117070 ↗
18. Culig L, Chu X, Bohr VA. Neurogenesis in aging and age-related neurodegenerative diseases. Ageing Res Rev. 2022;78:101636. https://doi.org/10.1016/j.arr.2022.101636.10.1016/j.arr.2022.101636 ↗
19. Dong N, Ali-Khiavi P, Ghavamikia N, Pakmehr S, Sotoudegan F, Hjazi A, et al. Nanomedicine in the treatment of Alzheimer’s disease: bypassing the blood-brain barrier with cutting-edge nanotechnology. Neurol Sci. 2025;46(4):1489–507. https://doi.org/10.1007/s10072-024-07871-4.10.1007/s10072-024-07871-4 ↗
20. Ellman GL, Courtney KD, Andres V, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961;7(2):88–95. https://doi.org/10.1016/0006-2952(61)90145-9.10.1016/0006-2952(61)90145-9 ↗
21. Elsaesser A, Howard CV. Toxicology of nanoparticles. Adv Drug Deliv Rev. 2012;64(2):129–37.10.1016/j.addr.2011.09.001 ↗
22. Elsayed I, Abdelbary AA, Elshafeey AH. Nanosizing of a poorly soluble drug: technique optimization, factorial analysis, and pharmacokinetic study in healthy human volunteers. Int J Nanomedicine. 2014;9:2943–53. https://doi.org/10.2147/IJN.S63395.10.2147/IJN.S63395 ↗
23. Fania A, Monaco A, Amoroso N, Bellantuono L, Cazzolla Gatti R, Firza N, et al. A dementia mortality rates dataset in Italy (2012–2019). Sci Data. 2023;10(1):564.10.1038/s41597-023-02461-z ↗
24. Gao T, Xu H, Jia S, Cai Z, Chen B, Fan G, et al. Magnolol induces human Ewing sarcoma SK-ES-1 cell apoptosis via the mitochondrial and death receptor pathways. Am J Transl Res. 2020;12(5):1672.
25. Gáspár A, Hutka B, Ernyey AJ, Tajti BT, Varga BT, Zádori ZS, et al. Performance of the intracerebroventricularly injected streptozotocin Alzheimer’s disease model in a translationally relevant, aged and experienced rat population. Sci Rep. 2022;12(1):20247. https://doi.org/10.1038/s41598-022-24292-5.10.1038/s41598-022-24292-5 ↗
26. Grayson B, Leger M, Piercy C, Adamson L, Harte M, Neill JC. Assessment of disease-related cognitive impairments using the novel object recognition (NOR) task in rodents. Behav Brain Res. 2015;285:176–93. https://doi.org/10.1016/j.bbr.2014.10.025.10.1016/j.bbr.2014.10.025 ↗
27. Hampel H, Vassar R, De Strooper B, Hardy J, Willem M, Singh N, et al. The β-Secretase BACE1 in Alzheimer’s Disease. Biol Psychiatry. 2021;89(8):745–56. https://doi.org/10.1016/j.biopsych.2020.02.001.10.1016/j.biopsych.2020.02.001 ↗
28. Hao L, Zhong X, Yu R, Chen J, Li W, Chen Y, et al. Integrating network pharmacology and experimental validation to Decipher the anti-inflammatory effects of magnolol on LPS-inducedRAW264.7 cells. Comb Chem High Throughput Screen. 2024;27(3):462–78. https://doi.org/10.2174/0113862073255964230927105959.10.2174/0113862073255964230927105959 ↗
29. Hu L, Tao Y, Jiang Y, Qin F. Recent progress of nanomedicine in the treatment of Alzheimer’s disease. Front Cell Dev Biol. 2023;11:1228679. https://doi.org/10.3389/fcell.2023.1228679.10.3389/fcell.2023.1228679 ↗
30. Huang H, Su L, Sun Y, Li B, Deng J, Cao Z. Dietary magnolol inclusion improves the antioxidant and immune responses, and resistance to Aeromonas hydrophila in genetically improved farmed tilapia (Oreochromis niloticus). Aquac Rep. 2022;23:101017.10.1016/j.aqrep.2022.101017 ↗
31. Igartúa DE, Gómez Martínez C, Alonso S del V, Prieto MJ. Combined therapy for Alzheimer’s disease. AAPS PharmSciTech 2020;21. https://sedici.unlp.edu.ar/handle/10915/13923710.1208/s12249-020-01652-w ↗
32. Jia J, Zhao S, Zhao J, Gao Y. Engineered nanoparticles for the treatment of Alzheimer’s disease. Front Pharmacol. 2025;16:1510798. https://doi.org/10.3389/fphar.2025.1510798.10.3389/fphar.2025.1510798 ↗
33. Joe E, Ringman JM. Cognitive symptoms of Alzheimer’s disease: clinical management and prevention. BMJ. 2019;367:l6217. https://doi.org/10.1136/bmj.l6217.10.1136/bmj.l6217 ↗
34. Kaliappan S, Liu C, Jain Y, Karkar R, Saha K. Online communities as a support system for Alzheimer Disease and Dementia Care: large-scale exploratory study. JMIR Aging. 2025;8(1):e68890. https://doi.org/10.2196/68890.10.2196/68890 ↗
35. Kareva I. The many roads to dementia: A systems view of Alzheimer’s disease (No. arXiv:2504.05441). arXiv. 2025. https://doi.org/10.48550/arXiv.2504.0544110.48550/arXiv.2504.05441 ↗
36. Knezovic A, Hosch M, Hamann CS, Popp S, Ortega G, Osmanovic-Barilar J, et al. Approaching therapy of Alzheimer’s disease via the antidiabetic drug liraglutide: a study with streptozotocin intracerebroventricularly treated Wistar rats. J Neural Transm. 2025. https://doi.org/10.1007/s00702-025-02979-z.10.1007/s00702-025-02979-z ↗
37. Knezovic A, Osmanovic-Barilar J, Curlin M, Hof PR, Simic G, Riederer P, et al. Staging of cognitive deficits and neuropathological and ultrastructural changes in streptozotocin-induced rat model of Alzheimer’s disease. J Neural Transm. 2015;122(4):577–92. https://doi.org/10.1007/s00702-015-1394-4.10.1007/s00702-015-1394-4 ↗
38. Kraeuter A-K, Guest PC, Sarnyai Z. The Y-maze for assessment of spatial working and reference memory in mice. In: Guest PC, editor. Pre-clinical models. Springer New York; 2019. Vol. 1916, pp. 105–111. https://doi.org/10.1007/978-1-4939-8994-2_1010.1007/978-1-4939-8994-2_10 ↗
39. Labban S, Alghamdi BS, Alshehri FS, Kurdi M. Effects of melatonin and resveratrol on recognition memory and passive avoidance performance in a mouse model of Alzheimer’s disease. Behav Brain Res. 2021;402:113100. https://doi.org/10.1016/j.bbr.2020.113100.10.1016/j.bbr.2020.113100 ↗
40. Li H, Zhao Z, Fassini A, Lee HK, Green RJ, Gomperts SN. Impaired hippocampal circuit function underlying memory encoding and consolidation precede robust Aβ deposition in a mouse model of alzheimer’s disease. Sci Rep. 2025;15(1):21957. https://doi.org/10.1038/s41598-025-05653-2.10.1038/s41598-025-05653-2 ↗
41. Lin Y, Li Y, Zeng Y, Tian B, Qu X, Yuan Q, et al. Pharmacology, toxicity, bioavailability, and formulation of magnolol: an update. Front Pharmacol. 2021;12:632767.10.3389/fphar.2021.632767 ↗
42. Liu S, Jie C, Zheng W, Cui J, Wang Z. Investigation of underlying association between whole brain regions and Alzheimer’s disease: a research based on an artificial intelligence model. Front Aging Neurosci. 2022;14:872530.10.3389/fnagi.2022.872530 ↗
43. Lu Q, Meng Y, Feng H, Di X, Guo X. Evaluation of the anti-Alzheimer activity of Lycium barbarum polysaccharide in Aβ1–42-induced neurotoxicity in rat model. Curr Issues Mol Biol. 2025;47(4):Article 4. https://doi.org/10.3390/cimb47040226.10.3390/cimb47040226 ↗
44. Lueptow LM. Novel object recognition test for the investigation of learning and memory in mice. J Vis Exp. 2017;126:55718.
45. Mertaş B, Boşgelmez İİ. The role of genetic, environmental, and dietary factors in Alzheimer’s disease: a narrative review. Int J Mol Sci. 2025;26(3):1222. https://doi.org/10.3390/ijms26031222.10.3390/ijms26031222 ↗
46. Millot P, San C, Bennana E, Porte B, Vignal N, Hugon J, et al. STAT3 inhibition protects against neuroinflammation and BACE1 upregulation induced by systemic inflammation. Immunol Lett. 2020;228:129–34. https://doi.org/10.1016/j.imlet.2020.10.004.10.1016/j.imlet.2020.10.004 ↗
47. Mohapatra TK, Nayak RR, Ganeshpurkar A, Tiwari P, Kumar D. Navigating the treatment landscape of Alzheimer’s disease: current strategies and future directions. Ibrain. 2025;11(2):162–84. https://doi.org/10.1002/ibra.12197.10.1002/ibra.12197 ↗
48. Moreira-Silva D, Vizin RCL, Martins TMS, Ferreira TL, Almeida MC, Carrettiero DC. Intracerebral injection of streptozotocin to model Alzheimer disease in rats. Bio Protoc. 2019;9(20):e3397. https://doi.org/10.21769/BioProtoc.3397.PMID:33654898;PMCID:PMC7853929.10.21769/BioProtoc.3397.PMID:33654898;PMCID:PMC7853929 ↗
49. Moreta MP-G, Burgos-Alonso N, Torrecilla M, Marco-Contelles J, Bruzos-Cidón C. Efficacy of acetylcholinesterase inhibitors on cognitive function in Alzheimer’s disease. Rev Rev Biomed. 2021;9(11):1689. https://doi.org/10.3390/biomedicines9111689.10.3390/biomedicines9111689 ↗
50. Noor NA, Hosny EN, Khadrawy YA, Mourad IM, Othman AI, Aboul Ezz HS, et al. Effect of curcumin nanoparticles on streptozotocin-induced male Wistar rat model of Alzheimer’s disease. Metab Brain Dis. 2022;37(2):343–57. https://doi.org/10.1007/s11011-021-00897-z.10.1007/s11011-021-00897-z ↗
51. Oehlrich D, Peschiulli A, Tresadern G, Van Gool M, Vega JA, De Lucas AI, et al. Evaluation of a series of β-secretase 1 inhibitors containing novel heteroaryl-fused-piperazine amidine warheads. ACS Med Chem Lett. 2019;10(8):1159–65. https://doi.org/10.1021/acsmedchemlett.9b00181.10.1021/acsmedchemlett.9b00181 ↗
52. Olas B. The cardioprotective effect of Magnolia officinalis and its major bioactive chemical constituents. Int J Mol Sci. 2025;26(9):4380.10.3390/ijms26094380 ↗
53. Panegyres PK, Chen H-Y. Differences between early and late onset Alzheimer’s disease. Am J Neurodegener Dis. 2013;2(4):300–6.
54. Parray HA, Lone J, Park JP, Choi JW, Yun JW. Magnolol promotes thermogenesis and attenuates oxidative stress in 3T3-L1 adipocytes. Nutrition. 2018;50:82–90.10.1016/j.nut.2018.01.017 ↗
55. Puranik N, Kumari M, Tiwari S, Dhakal T, Song M. Resveratrol as a therapeutic agent in Alzheimer’s disease: evidence from clinical studies. Nutrients. 2025;17(15):2557. https://doi.org/10.3390/nu17152557.10.3390/nu17152557 ↗
56. Qiao A, Li J, Hu Y, Wang J, Zhao Z. Reduction BACE1 expression via suppressing NF-κB mediated signaling by Tamibarotene in a mouse model of Alzheimer’s disease. IBRO Neurosci Rep. 2021;10:153–60. https://doi.org/10.1016/j.ibneur.2021.02.004.10.1016/j.ibneur.2021.02.004 ↗
57. Rabinovici GD. Late-onset Alzheimer disease. Continuum. 2019;25(1):14–33. https://doi.org/10.1212/CON.0000000000000700.10.1212/CON.0000000000000700 ↗
58. Rossier B, Jordan O, Allémann E, Rodríguez-Nogales C. Nanocrystals and nanosuspensions: an exploration from classic formulations to advanced drug delivery systems. Drug Deliv Transl Res. 2024;14(12):3438–51. https://doi.org/10.1007/s13346-024-01559-0.10.1007/s13346-024-01559-0 ↗
59. Sahraei R, Aminyavari S, Hosseini M, Hassanzadeh-Taheri M, Foadoddini M, Saebipour MR. The ameliorative impact of Centella asiatica on the working memory deficit in Streptozotocin-induced rat model of Alzheimer disease. Basic Clin Neurosci J. 2022;13(1):25–34. https://doi.org/10.32598/bcn.2021.144.4.10.32598/bcn.2021.144.4 ↗
60. Salkovic-Petrisic M, Knezovic A, Hoyer S, Riederer P. What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer’s disease, about the therapeutic strategies in Alzheimer’s research. J Neural Transm. 2013;120(1):233–52. https://doi.org/10.1007/s00702-012-0877-9.10.1007/s00702-012-0877-9 ↗
61. Salkovic-Petrisic M, Perhoc AB, Homolak J, Knezovic A, Osmanovic Barilar J, Riederer P. Experimental approach to Alzheimer’s disease with emphasis on insulin resistance in the brain. In: Handbook of neurotoxicity. Cham: Springer; 2022. p. 1657–708. https://doi.org/10.1007/978-3-031-15080-7_98.10.1007/978-3-031-15080-7_98 ↗
62. Scheltens P, Strooper BD, Kivipelto M, Holstege H, Chételat G, Teunissen CE, et al. Alzheimer’s disease. Lancet. 2021;397(10284):1577–90. https://doi.org/10.1016/S0140-6736(20)32205-4.10.1016/S0140-6736(20)32205-4 ↗
63. Scioscia NP, Pensel PE, Denegri GM, Elissondo MC. Development of an improved anesthesia protocol to increase CF1 mice survival in a portal vein infection with Echinococcus granulosus sensu lato protoscoleces. Heliyon. 2021;7(3):e06496. https://doi.org/10.1016/j.heliyon.2021.e06496.10.1016/j.heliyon.2021.e06496 ↗
64. Shao S, Ye X, Su W, Wang Y. Curcumin alleviates Alzheimer’s disease by inhibiting inflammatory response, oxidative stress and activating the AMPK pathway. J Chem Neuroanat. 2023;134:102363. https://doi.org/10.1016/j.jchemneu.2023.102363.10.1016/j.jchemneu.2023.102363 ↗
65. Silva SSL, Tureck LV, Souza LC, Mello-Hortega JV, Piumbini AL, Teixeira MD, et al. Animal model of Alzheimer’s disease induced by streptozotocin: new insights about cholinergic pathway. Brain Res. 2023;1799:148175. https://doi.org/10.1016/j.brainres.2022.148175.10.1016/j.brainres.2022.148175 ↗
66. Sivamaruthi BS, Raghani N, Chorawala M, Bhattacharya S, Prajapati BG, Elossaily GM, et al. NF-κB pathway and its inhibitors: a promising frontier in the management of Alzheimer’s disease. Biomedicines. 2023;11(9):2587. https://doi.org/10.3390/biomedicines11092587.10.3390/biomedicines11092587 ↗
67. Sonkusare S, Srinivasan K, Kaul C, Ramarao P. Effect of donepezil and lercanidipine on memory impairment induced by intracerebroventricular streptozotocin in rats. Life Sci. 2005;77(1):1–14. https://doi.org/10.1016/j.lfs.2004.10.036.10.1016/j.lfs.2004.10.036 ↗
68. Sultana N, Sayeed MA, Islam M, Azad SAK, Tareq SB, Yeasmin F. Potential role of Magnolol: a comprehensive review on its efficacy in managing neurological disorders. Brain Disord. 2025. https://doi.org/10.1016/j.dscb.2025.100231.10.1016/j.dscb.2025.100231 ↗
69. Sun E, Motolani A, Campos L, Lu T. The pivotal role of NF-kB in the pathogenesis and therapeutics of Alzheimer’s disease. Int J Mol Sci. 2022;23(16):8972. https://doi.org/10.3390/ijms23168972.10.3390/ijms23168972 ↗
70. Sun N, Deng X, Kong H, Zhi Z, Jiang G, Xiong J, et al. Magnolol as an antibacterial agent against drug-resistant bacteria targeting filamentous temperature-sensitive mutant Z. Chem Biodivers. 2025;22(5):e202402800. https://doi.org/10.1002/cbdv.202402800.10.1002/cbdv.202402800 ↗
71. Szałabska-Rąpała K, Borymska W, Kaczmarczyk-Sedlak I. Effectiveness of magnolol, a lignan from Magnolia bark, in diabetes, its complications and comorbidities: a review. Int J Mol Sci. 2021;22(18):10050.10.3390/ijms221810050 ↗
72. Tai XY, Veldsman M, Lyall DM, Littlejohns TJ, Langa KM, Husain M, et al. Cardiometabolic multimorbidity, genetic risk, and dementia: a prospective cohort study. Lancet Healthy Longev. 2022;3(6):e428–36. https://doi.org/10.1016/S2666-7568(22)00117-9.10.1016/S2666-7568(22)00117-9 ↗
73. Tamagno E, Guglielmotto M, Vasciaveo V, Tabaton M. Oxidative stress and beta amyloid in Alzheimer’s disease which comes first: the chicken or the egg? Antioxid Basel. 2021;10(9):Article 9. https://doi.org/10.3390/antiox10091479.10.3390/antiox10091479 ↗
74. Tocci D, Fogel M, Gupta V, Kim P, Latimer J, Adlimoghaddam A, et al. Beyond expectations: investigating nilotinib’s potential in attenuating neurodegeneration in Alzheimer’s disease. Alzheimers Res Ther. 2025;17(1):60. https://doi.org/10.1186/s13195-025-01706-w.10.1186/s13195-025-01706-w ↗
75. Vorhees CV, Williams MT. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc. 2006;1(2):848–58.10.1038/nprot.2006.116 ↗
76. Wang C, Guo J, Guo R. Effect of XingPiJieYu decoction on spatial learning and memory and cAMP-PKA-CREB-BDNF pathway in rat model of depression through chronic unpredictable stress. BMC Complement Altern Med. 2017;17(1):73. https://doi.org/10.1186/s12906-016-1543-9.10.1186/s12906-016-1543-9 ↗
77. Wang H, Yan Z, Yang W, Liu R, Fan G, Gu Z, et al. A strategy of monitoring acetylcholinesterase and screening of natural inhibitors from *Uncaria* for Alzheimer’s disease therapy based on near-infrared fluorescence probe. Sens Actuators B Chem. 2025;424:136895. https://doi.org/10.1016/j.snb.2024.136895.10.1016/j.snb.2024.136895 ↗
78. Wang X, Jia J. Magnolol improves Alzheimer’s disease-like pathologies and cognitive decline by promoting autophagy through activation of the AMPK/mTOR/ULK1 pathway. Biomed Pharmacother. 2023;161:114473.10.1016/j.biopha.2023.114473 ↗
79. Wang X, Liu Q, Fu Y, Ding R-B, Qi X, Zhou X, et al. Magnolol as a potential anticancer agent: a proposed mechanistic insight. Molecules. 2022;27(19):6441.10.3390/molecules27196441 ↗
80. Xian Y-F, Qu C, Liu Y, Ip S-P, Yuan Q-J, Yang W, et al. Magnolol ameliorates behavioral impairments and neuropathology in a transgenic mouse model of Alzheimer’s disease. Oxid Med Cell Longev. 2020;2020(1):5920476. https://doi.org/10.1155/2020/5920476.10.1155/2020/5920476 ↗
81. Xu Y, Liu X, Lian R, Zheng S, Yin Z, Lu Y, et al. Enhanced dissolution and oral bioavailability of aripiprazole nanosuspensions prepared by nanoprecipitation/homogenization based on acid–base neutralization. Int J Pharm. 2012;438(1–2):287–95.10.1016/j.ijpharm.2012.09.020 ↗
82. Yang H, Tan H, Wen H, Xin P, Liu Y, Deng Z, et al. Recent progress in nanomedicine for the diagnosis and treatment of Alzheimer’s diseases. ACS Nano. 2024;18(50):33792–826. https://doi.org/10.1021/acsnano.4c11966.10.1021/acsnano.4c11966 ↗
83. Yu J, Gao X, Zhang L, Shi H, Yan Y, Han Y, et al. Magnolol extends lifespan and improves age-related neurodegeneration in *Caenorhabditis elegans* via increase of stress resistance. Sci Rep. 2024;14(1):3158. https://doi.org/10.1038/s41598-024-53374-9.10.1038/s41598-024-53374-9 ↗
84. Zhan Q, Kong F, Shao S, Zhang B, Huang S. Pathogenesis of depression in Alzheimer’s disease. Neurochem Res. 2024;49(3):548–56. https://doi.org/10.1007/s11064-023-04061-0.10.1007/s11064-023-04061-0 ↗
85. Zhang L, Ding X, Wu Z, Wang M, Tian M. Curcumin alleviates pain and improves cognitive impairment in a rat model of cobra venom-induced trigeminal neuralgia. J Pain Res. 2018;11:1095–104. https://doi.org/10.2147/JPR.S162668.10.2147/JPR.S162668 ↗
86. Zhang W, Lukacsovich D, Young JI, Gomez L, Schmidt MA, Martin ER, et al. DNA methylation signature of a lifestyle-based resilience index for cognitive health. Alzheimers Res Ther. 2025;17(1):88. https://doi.org/10.1186/s13195-025-01733-7.10.1186/s13195-025-01733-7 ↗
87. Zhou J, Singh N, Galske J, Hudobenko J, Hu X, Yan R. BACE1 regulates expression of clusterin in astrocytes for enhancing clearance of β-amyloid peptides. Mol Neurodegener. 2023;18(1):31. https://doi.org/10.1186/s13024-023-00611-w.10.1186/s13024-023-00611-w ↗