Manuka Honey Reduces Amyloid-β–Induced Neurotoxicity via Oxidative Stress Pathways
Navarro-Hortal MD, Romero-Márquez JM, Muñoz-Ollero P, Jiménez-Trigo V, Esteban-Muñoz A, Tutusaus K, Giampieri F, Battino M, Sánchez-González C, Rivas-García L, Llopis J, Forbes-Hernández TY, Quiles JL. Amyloid β-but not Tau-induced neurotoxicity is suppressed by Manuka honey via HSP-16.2 and SKN-1/Nrf2 pathways in an in vivo model of Alzheimer’s disease. Food Funct 2022;13(21):11185-11199. doi: 10.1039/d2fo01739c.
Background: Alzheimer’s disease is a progressive neurodegenerative disorder characterized by β-amyloid (Aβ) aggregation and hyperphosphorylated Tau tangles, processes linked to oxidative stress. Natural products with antioxidant properties may ameliorate these pathologies, but the neuroprotective effects of Manuka honey (MH) had not been previously studied.
Hypothesis: This study hypothesized that Manuka honey could alleviate Aβ- and Tau-induced neurotoxicity in Caenorhabditis elegans through modulation of oxidative stress–related pathways.
Methods: The authors used several C. elegans strains, including Aβ- and Tau-expressing transgenics, to evaluate MH effects on oxidative stress, paralysis and locomotion. Phenolic composition and antioxidant capacity were measured, and RNA interference assays targeted stress-related genes. Locomotion parameters such as swimming speed, wavelength, and activity were analyzed using WormLab and the WormLab Imaging System.
Results: Manuka honey significantly reduced reactive oxygen species levels and delayed Aβ-induced paralysis, decreasing β-amyloid aggregation. RNAi experiments indicated that its protective effects required HSP-16.2 and SKN-1/Nrf2 pathways, while DAF-16 was not involved. Conversely, MH impaired locomotion in both wild-type and Tau-transgenic worms, an effect attributed to its sugar content rather than Tau aggregation.
Conclusions: Manuka honey improved oxidative stress resistance and reduced Aβ-induced neurotoxicity via HSP-16.2 and SKN-1/Nrf2 pathways, but its sugars negatively affected locomotor behavior. The study suggests that MH’s antioxidant activity underlies its selective neuroprotective effects.
