Karthik Chintharala¹*, Amritaa Thalla²

¹NRI Academy of Medical Sciences, Guntur, India
²Maheshwara Medical College and Hospital, Telangana, India

*Corresponding Author: Karthik Chintharala, NRI Academy of Medical Sciences, Guntur, India.

Received: May 18, 2026; Published: July 07, 2026

Abstract

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β deposition, tau hyperphosphorylation, mitochondrial dysfunction, oxidative stress, chronic neuroinflammation, synaptic degeneration, and neuronal loss. Although currently available therapies, including acetylcholinesterase inhibitors such as donepezil, NMDA receptor antagonists such as memantine, and anti-amyloid monoclonal antibodies such as donanemab and lecanemab, provide symptomatic or modest disease-modifying benefits, their overall clinical impact remains limited. These limitations have increased interest in naturally derived compounds capable of targeting multiple neuropathological pathways implicated in Alzheimer’s disease. Among these, Litchi chinensis has emerged as a rich source of bioactive phytochemicals with potential neuroprotective properties.

Review Focus: A comprehensive review of the available literature was conducted to evaluate the neuroprotective potential of Litchi chinensis and its phytoconstituents in Alzheimer’s disease. Experimental studies investigating the effects of lychee-derived compounds on amyloid pathology, tau dysfunction, oxidative stress, neuroinflammation, apoptosis, synaptic impairment, and neuronal survival were critically synthesized.

Key Findings: Preclinical studies suggest that Litchi chinensis-derived compounds, including catechins, procyanidins, flavanols, saponins, and oligonol, exert neuroprotective effects through multiple complementary mechanisms. These phytochemicals have been reported to reduce amyloidogenic processing by modulating amyloid precursor protein and β-secretase activity, suppress tau hyperphosphorylation through regulation of the IRS-1/PI3K/Akt/GSK-3β signaling pathway, attenuate oxidative stress by enhancing endogenous antioxidant defences, and inhibit neuroinflammatory responses involving NF-κB and NLRP3 signaling. Additional reported effects include modulation of apoptotic pathways, preservation of synaptic proteins and blood–brain barrier integrity, enhancement of autophagy, and regulation of neurotrophic and metabolic signaling pathways associated with neuronal survival and cognitive function.

Future Perspectives: Current preclinical evidence suggests that Litchi chinensis and its bioactive constituents warrant further investigation as potential adjunctive therapeutic candidates for Alzheimer’s disease. However, clinical translation remains limited, and additional studies are required to establish standardized formulations, characterize pharmacokinetic properties, evaluate long- term safety, and determine therapeutic efficacy in human populations.

Keywords: Alzheimer’s Disease; Litchi chinensis; Lychee; Oligonol; Polyphenols; Amyloid-Β; Tau; Neuroinflammation; Oxidative Stress; Neuroprotection

References

1. Mayeux R and Stern Y. “Epidemiology of Alzheimer disease”. Cold Spring Harbor Perspectives in Medicine 8 (2012): a006239.
2. World Health Organization. “Global status report on the public health response to dementia”. WHO (2021).
3. Sohrabi HR and Weinborn M. “Cognitive Impairments in Alzheimer's Disease and Other Neurodegenerative Diseases”. In Neurodegeneration and Alzheimer's Disease (eds R. N. Martins, C.S. Brennan, W.M.A.D.B. Fernando, M.A. Brennan and S.J. Fuller) (2019).
4. Guerchet M., et al. “Numbers of people with dementia worldwide: an update to the estimates in the World Alzheimer Report”. Alzheimer’s Disease International (2017).
5. Harris GA., et al. “Revisiting the therapeutic landscape of tauopathies: assessing the current pipeline and clinical trials”. Alzheimer’s Research Therapy1 (2025): 129.
6. de Felice FG., et al. “Aβ oligomers induce neuronal oxidative stress and synaptic dysfunction”. Journal of Biological Chemistry 279 (2004): 33139-33145.
7. Wang X., et al. “Oxidative stress and mitochondrial dysfunction in Alzheimer's disease”. Biochimica et Biophysica Acta8 (2014): 1240-1247.
8. Tönnies E and Trushina E. “Oxidative stress, synaptic dysfunction, and mitochondrial failure in Alzheimer’s disease”. Journal of Alzheimer's Disease 57 (2017): 1105-1121.
9. Hansen RA., et al. “Efficacy and safety of donepezil, galantamine, and rivastigmine for Alzheimer’s disease”. Clinical Interventions in Aging 3 (2008): 211-225.
10. Wrigley S., et al. “Monoclonal Antibody Therapies in Alzheimer's Disease: A Guide for Emergency Physicians”. Emergency Medicine Australasia6 (2025): e70167.
11. Yashooa RK., et al. “CRISPR-Cas technologies in neurodegenerative disorders: mechanistic insights, therapeutic potential, and translational challenges”. Frontiers in Neurology 16 (2026): 1737468.
12. Iqubal A., et al. “Current Quest in Natural Bioactive Compounds for Alzheimer’s Disease: Multi-Targeted-Designed-Ligand Based Approach with Preclinical and Clinical Based Evidence”. Current Drug Targets 22 (2021): 685-720.
13. Chen B., et al. “Neuroprotective effects of natural compounds on neurotoxin-induced oxidative stress and cell apoptosis”. Nutritional Neuroscience5 (2022): 1078-1099.
14. Shoaib S., et al. “Plant-Derived Bioactive Compounds in the Management of Neurodegenerative Disorders: Challenges, Future Directions and Molecular Mechanisms Involved in Neuroprotection”. Pharmaceutics 3 (2023): 749.
15. A Mohamed., et al. “Litchi chinensis: Medicinal uses, phytochemistry, and pharmacology”. Journal of Ethnopharmacology 174 (2015).
16. Kanwal Rabia., et al. (2024). Litchi.
17. Choi YY., et al. “Oligonol improves memory and cognition under an amyloid β (25-35)-induced Alzheimer's mouse model”. Nutrition Research7 (2014): 595-603.
18. Desai MK., et al. “Triple-transgenic Alzheimer's disease mice exhibit region-specific abnormalities in brain myelination patterns prior to appearance of amyloid and tau pathology”. Glia1 (2009): 54-65.
19. Jo Y., et al. “Oligonol enhances mitochondrial and synaptic function in aged and Alzheimer’s disease models”. Ageing Research Review (2023).
20. Ibrahim SR and Mohamed GA. “Litchi chinensis: medicinal uses, phytochemistry, and pharmacology”. Journal of Ethnopharmacology 174 (2015): 492-513.
21. Wang X., et al. “Inhibitory Effect of Lychee Seed Saponins on Apoptosis Induced by Aβ25-35 through Regulation of the Apoptotic and NF-κB Pathways in PC12 Cells”. Nutrients4 (2017): 337.
22. Habtemariam S. “Natural Products in Alzheimer's Disease Therapy: Would Old Therapeutic Approaches Fix the Broken Promise of Modern Medicines?” Molecules8 (2019): 1519.
23. Lee AY., et al. “Preventive effect of oligonol on nitric oxide and reactive oxygen species production through regulation of nuclear factor kappa B signaling pathway in RAW 264.7 macrophage cells against sodium nitroprusside”. RSC Advances7 (2019): 3987-3993.
24. Choi SY., et al. “Oligonol enhances brain cognitive function in high-fat diet-fed mice”. Biomed Pharmacotherapy 179 (2024): 117322.
25. Xiong R., et al. “Polyphenols isolated from lychee seed inhibit Alzheimer's disease-associated Tau through improving insulin resistance via the IRS-1/PI3K/Akt/GSK-3β pathway”. Journal of Ethnopharmacology 251 (2020): 112548.
26. Haass C and Selkoe DJ. “Cellular processing of beta-amyloid precursor protein and the genesis of amyloid beta-peptide”. Cell 6 (1993): 1039-1042.
27. Tang Y., et al. “Polyphenols Derived from Lychee Seed Suppress Aβ (1-42)-Induced Neuroinflammation”. International Journal of Molecular Sciences7 (2018): 2109.
28. Barbier P., et al. “Role of Tau as a Microtubule-Associated Protein: Structural and Functional Aspects”. Frontiers in Aging Neuroscience 11 (2019): 204.
29. Long HZ., et al. “PI3K/AKT Signal Pathway: A Target of Natural Products in the Prevention and Treatment of Alzheimer's Disease and Parkinson's Disease”. Frontiers in Pharmacology 12 (2021): 648636.
30. Heneka MT., et al. “Neuroinflammation in Alzheimer's disease”. Lancet Neurology4 (2015): 388-405.
31. Xiong R., et al. “Lychee seed polyphenol protects the blood-brain barrier through inhibiting Aβ (25-35)-induced NLRP3 inflammasome activation via the AMPK/mTOR/ULK1-mediated autophagy in bEnd.3 cells and APP/PS1 mice”. Phytotherapy Research2 (2021): 954-973.
32. Tönnies E and Trushina E. “Oxidative Stress, Synaptic Dysfunction, and Alzheimer's Disease”. Journal of Alzheimer’s Disease4 (2017): 1105-1121.
33. Jo D., et al. “Oligonol ameliorates liver function and brain function in the 5 × FAD mouse model: transcriptional and cellular analysis”. Food Function21 (2023): 9650-9670.
34. Tu S., et al. “Oligomeric Aβ-induced synaptic dysfunction in Alzheimer's disease”. Molecular Neurodegeneration 9 (2014): 48.
35. Budson Andrew E. author.; Solomon, Paul R., author. Edinburgh: Elsevier; 2016 Library Catalog; MMS ID 9916673333406676; ISBN 9780323286619; NLM Unique ID 101667333.
36. Qiu WQ., et al. “Lychee seed polyphenol inhibits Aβ-induced activation of NLRP3 inflammasome via the LRP1/AMPK mediated autophagy induction”. Biomed Pharmacotherapy 130 (2020): 110575.
37. Cryan JF., et al. “The gut microbiome in neurological disorders”. Lancet Neurology2 (2020): 179-194.
38. Chintharala K., et al. “The Gut Microbiome And Its Impact On Neurological Health: A Systematic Review”. Journal of Neurological Sciences and Research1 (2024).
39. Cummings J., et al. “Alzheimer's disease drug development pipeline: 2021”. Alzheimer’s Dement (N Y)1 (2021): e12179.
40. Ringman JM., et al. “A potential role of the curry spice curcumin in Alzheimer's disease”. Current Alzheimer Research 2 (2005): 131-136.
41. Thirunavukkarasu M., et al. “Safety of oligonol, a highly bioavailable lychee-derived polyphenolic antioxidant, on liver, kidney and heart function in rats”. Toxicology Mechanisms and Methods7 (2012): 555-559.

Citation

Citation: Karthik Chintharala and Amritaa Thalla. “From Lychee to Neurotherapeutics: Mechanistic, Gut–Brain, and Translational Perspectives on Litchi chinensis in Alzheimer’s Disease". Acta Scientific Neurology 9.7 (2026): 33-42.

Copyright

Copyright: ©2026 Karthik Chintharala and Amritaa Thalla. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.