Long-Term Ingestion of Sicilian Black Bee Chestnut Honey and/or D-Limonene Counteracts Brain Damage Induced by High Fat-Diet in Obese Mice

• Published in: International journal of molecular sciences Vol. 24; no. 4; p. 3467
• Main Authors: Terzo, Simona, Calvi, Pasquale, Nuzzo, Domenico, Picone, Pasquale, Allegra, Mario, Mulè, Flavia, Amato, Antonella
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.02.2023; MDPI
• Subjects: Alzheimer's disease; Amyloid; Analysis; Animals; Apoptosis; Bees; BIM protein; Brain - metabolism; Brain damage; Brain Injuries - metabolism; Brain injury; Brain-derived neurotrophic factor; D-limonene; Diet; Diet, High-Fat; Eating; Gene expression; Genes; High fat diet; Honey; Inflammation; Inflammation - metabolism; Ingestion; Interleukin 6; Limonene; Mice; Mice, Inbred C57BL; Mice, Obese; Neurodegeneration; neuronal damage; Neurons; Nitric-oxide synthase; Obesity; Obesity - metabolism; Oils & fats; Oxidative stress; Phosphorylation; Tau protein; Tumor necrosis factor-α; D-limonene; neurodegeneration; neuronal damage; honey; obesity; high-fat diet
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24043467

Obesity is linked to neurodegeneration, which is mainly caused by inflammation and oxidative stress. We analyzed whether the long-term intake of honey and/or D-limonene, which are known for their antioxidant and anti-inflammatory actions, when ingested separately or in combination, can counteract the neurodegeneration occurring in high fat diet (HFD)-induced obesity. After 10 weeks of HFD, mice were divided into: HFD-, HFD + honey (HFD-H)-, HFD + D-limonene (HFD-L)-, HFD + honey + D-limonene (HFD-H + L)-fed groups, for another 10 weeks. Another group was fed a standard diet (STD). We analyzed the brain neurodegeneration, inflammation, oxidative stress, and gene expression of Alzheimer's disease (AD) markers. The HFD animals showed higher neuronal apoptosis, upregulation of pro-apoptotic genes Fas-L, Bim P27 and downregulation of anti-apoptotic factors BDNF and BCL2; increased gene expression of the pro-inflammatory IL-1β, IL-6 and TNF-α and elevated oxidative stress markers COX-2, iNOS, ROS and nitrite. The honey and D-limonene intake counteracted these alterations; however, they did so in a stronger manner when in combination. Genes involved in amyloid plaque processing (APP and TAU), synaptic function (Ache) and AD-related hyperphosphorylation were higher in HFD brains, and significantly downregulated in HFD-H, HFD-L and HFD-H + L. These results suggest that honey and limonene ingestion counteract obesity-related neurodegeneration and that joint consumption is more efficacious than a single administration.