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Review
. 2025 Jun 30.
doi: 10.1007/s13346-025-01906-9. Online ahead of print.

Plant-based flavonoids and their nanoparticles: Latest arsenal against Alzheimer's disease

Popat S Kumbhar #  1 , Kaustubh Ajit Kolekar #  2 , Sukriti Vishwas  3 , Vikas Kamble  4 , Bushra Bashir  2 , Kalpana S Patil  5 , Durgacharan Bhagwat  6 , Guarav Gupta  7   8 , Parteek Prasher  9 , Manisha Singh  10 , Sachin Kumar Singh  11   12 , John Disouza  13 , Vandana B Patravale  14
Affiliations
Review

Plant-based flavonoids and their nanoparticles: Latest arsenal against Alzheimer's disease

Popat S Kumbhar et al. Drug Deliv Transl Res. .

Abstract

Alzheimer's disease (AD) is the most prevalent and emerging neurodegenerative disease and serves as the seventh biggest cause of mortality across the globe. The pathogenesis of AD is linked with multiple hallmarks. The applications of anti-AD therapeutics approved by the FDA have been restricted because of the least permeability, bioavailability, negative effects, and huge cost. Various flavonoids have attenuated the potential pathogenic biomarkers of Alzheimer's disease (AD) and reduced disease progression. However, the presence of the blood-brain barrier (BBB), limited permeability, bioavailability, and low stability are chief concerns associated with their delivery against AD. Therefore, they have been loaded into various nanoformulations, including PLGA nanoparticles, gold nanoparticles, NLCs, exosomes, cell membrane-coated nanocarriers, and microneedles, to improve brain targeting and enhance therapeutic effects at the site of action. This review focuses on the flavonoid as a potential natural therapeutics against AD. Diverse flavonoids explored to manage AD are discussed with their multiple anti-AD mechanisms. AD pathophysiology, current treatment strategies and its challenges, and the significance of using flavonoids against AD are explained. Moreover, role of NSCs in AD and potential of flavonoids in targeting NSCs is briefed. Challenges in the delivery of flavonoids against AD and diverse ground-breaking nanotechnological strategies employed to deliver these flavonoid-based therapeutics are discussed with manifold case studies. Also, the mechanisms of transport of NCs are explained. Further, flavonoids in clinical trials are briefed with conclusions and future concerns. In conclusion, flavonoid-based therapeutics and their delivery using breakthrough nanotechnological approaches hold promise for successfully managing AD.

Keywords: Alzheimer’s disease; Blood brain barriers; Clinical trials; Flavonoids; Nanocarriers; Neural stem cells.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not Applicable. Consent for publication: Not Applicable. Competing interests: The authors declare no competing interests.

References

    1. Hassan NA, Alshamari AK, Hassan AA, Elharrif MG, Alhajri AM, Sattam M, Khattab RR. Advances on therapeutic strategies for Alzheimer’s disease: from medicinal plant to nanotechnology. Molecules. 2022;27(15):4839. https://doi.org/10.3390/molecules27154839 . - DOI - PubMed - PMC
    1. Pei J, Kumarasamy RV, Jayaraman S, Kanniappan GV, Long Q, Palanisamy CP. Quercetin-functionalized nanomaterials: innovative therapeutic avenues for Alzheimer’s disease management. Ageing Res Rev. 2025;104: 102665. https://doi.org/10.1016/j.arr.2025.102665 . - DOI - PubMed
    1. Piccialli I, Tedeschi V, Caputo L, D’Errico S, Ciccone R, De Feo V, Secondo A, Pannaccione A. Exploring the therapeutic potential of phytochemicals in Alzheimer’s disease: focus on polyphenols and monoterpenes. Front Pharmacol. 2022;13:876614. https://doi.org/10.3389/fphar.2022.876614 . - DOI - PubMed - PMC
    1. Zhong X, Na Y, Yin S, Yan C, Gu J, Zhang N, Geng F. Cell membrane biomimetic nanoparticles with potential in treatment of Alzheimer’s disease. Molecules. 2023;28(5):2336. https://doi.org/10.3390/molecules28052336 . - DOI - PubMed - PMC
    1. He Z, Li X, Wang Z, Cao Y, Han S, Li N, Cai J, Cheng S, Liu Q. Protective effects of luteolin against amyloid beta-induced oxidative stress and mitochondrial impairments through peroxisome proliferator-activated receptor γ-dependent mechanism in Alzheimer’s disease. Redox Biol. 2023;66: 102848. https://doi.org/10.1016/j.redox.2023.102848 . - DOI - PubMed - PMC

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