Neuroprotective Properties of Litchi chinensis and Its Phytochemicals in Preclinical Models of Alzheimer's Disease.

PURPOSE: Alzheimer's disease (AD) is a progressive neurodegenerative disorder involving amyloid-β deposition, tau hyperphosphorylation, oxidative stress, and neuroinflammation. This review systematically evaluates the neuroprotective effects of Litchi chinensis and its phytochemicals against AD, focusing on modulation of Aβ accumulation, tau pathology, oxidative stress, neuroinflammation, apoptosis, and synaptic dysfunction using available preclinical evidence. METHOD: A systematic literature search was conducted in PubMed, Scopus, Web of Science, ScienceDirect, and Google Scholar up to August 2025 using relevant keywords. Studies investigating neuroprotective effects of Litchi chinensis extracts or compounds in in vitro or in vivo AD models were included, while unrelated studies, duplicates, abstracts, and non-full-text articles were excluded. RESULTS: Litchi chinensis extracts and phytochemicals demonstrated broad neuroprotective actions. In triple-transgenic mice, oligonol treatment (0.25-0.50 mg/mL) significantly reduced amyloid precursor protein (APP), β-secretase, and amyloid-β levels, while also decreasing tau hyperphosphorylation. Seed extracts (0.7-2.8 g/kg/day) reduced amyloid-β accumulation and neuronal injury in Sprague-Dawley rats. Anti-inflammatory effects were evident through decreased tumor necrosis factor-α, IL-1β, IL-6, and interferon gamma, alongside increased IL-4. Antioxidant defenses were enhanced via upregulation of antioxidant enzymes such as glutathione peroxidase-1 and superoxide dismutase-2, while apoptosis was suppressed by increasing Bcl-2 and reducing Bax and caspase activity. Synaptic integrity was preserved through upregulation of PSD95, synaptophysin, and serotonin receptor proteins, resulting in improved learning and memory in AD models. Additional benefits included enhanced mitochondrial and proteasomal activity, alleviation of endoplasmic reticulum (ER) stress, and induction of neurotrophic factors like insulin-like growth factor 2 and fibroblast growth factor 21. CONCLUSION: Litchi chinensis demonstrates a multitargeted neuroprotective role, making it a promising natural therapeutic candidate for Alzheimer's management. However, as most findings are limited to preclinical models, further clinical studies are necessary to validate efficacy, ensure safety, and explore its translational potential.