Honey as a Neuroprotective Agent: Molecular Perspectives on Its Role in Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is the most prevalent form of dementia and a major global health challenge, characterized by progressive cognitive decline and neurodegeneration. Despite decades of research, there is currently no cure, and available treatments provide only limited symptomatic relief without halting disease progression. In this context, natural compounds with multi-targeted biological activities are being explored as potential complementary therapeutic strategies. Honey, a complex natural substance rich in bioactive phytochemicals, has emerged as a promising candidate due to its antioxidant, anti-inflammatory, anti-apoptotic, and enzyme-inhibitory properties. This review summarizes the molecular mechanisms underlying the neuroprotective effects of honey in the context of AD, with a particular focus on its ability to modulate oxidative stress, mitochondrial dysfunction, inflammation, apoptosis, β-amyloid accumulation, tau hyperphosphorylation, and neurotransmission-related enzymes. Notably, the botanical origin of honey significantly influences its composition and biological activity, as evidenced by studies on avocado, manuka, acacia, kelulut, chestnut, coffee, or tualang honeys. While preclinical findings are encouraging, especially in vitro and in invertebrate and rodent models, clinical validation is still lacking. Therefore, further research, including well-designed in vivo and human studies, is needed to clarify the therapeutic relevance of honey in AD. Overall, honey may represent a promising natural adjunct in the prevention or management of AD, but current evidence remains preliminary.