Abstract
Obesity is a global epidemic that affects people of all ages, genders, and backgrounds. It can lead to a plethora of disorders, including diabetes mellitus, renal dysfunction, musculoskeletal problems, metabolic syndrome, cardiovascular, and neurodegenerative abnormalities. Obesity has also been linked to neurological diseases such as cognitive decline, dementia, and Alzheimer’s disease (AD), caused by oxidative stress, pro-inflammatory cytokines, and the production of reactive oxygen free radicals (ROS). Secretion of insulin hormone is impaired in obese people, leading to hyperglycaemia and increased accumulation of amyloid-β in the brain. Acetylcholine, a key neurotransmitter necessary for forming new neuronal connections in the brain, decreases in AD patients. To alleviate acetylcholine deficiency, researchers have proposed dietary interventions and adjuvant therapies that enhance the production of acetylcholine and assist in the management of AD patients. Such measures include dietary intervention with antioxidant and anti-inflammatory flavonoid-rich diets, which have been found to bind to tau receptors, reduce gliosis, and reduce neuroinflammatory markers in animal models. Furthermore, flavonoids like curcumin, resveratrol, epigallocatechin-3-gallate, morin, delphinidins, quercetin, luteolin, and oleocanthal have shown to cause significant reductions in interleukin-1β, increase BDNF levels, stimulate hippocampal neurogenesis and synapse formation, and ultimately prevent the loss of neurons in the brain. Thus, flavonoid-rich nutraceuticals can be a potential cost-effective therapeutic option for treating obesity-induced AD, but further well-designed, randomized, and placebo-controlled clinical studies are needed to assess their optimal dosages, efficacy, and long-term safety of flavonoids in humans. The main objectives of this review are to underscore the therapeutic potential of different nutraceuticals containing flavonoids that can be added in the daily diet of AD patients to enhance acetylcholine and reduce neuronal inflammation in the brain.
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Data availability
The data used and analyzed during the present study are available from the corresponding. Provided on reasonable request.
Abbreviations
- BDNF:
-
Brain-derived neurotrophic factor
- BBB:
-
Blood–brain barrier
- Aβ:
-
Amyloid beta
- IL-1β:
-
Interleukin-1β
- AD:
-
Alzheimer’s disease
- A:
-
Amyloid peptide
- IGF1:
-
Insulin-like growth factor-1
- MAPK:
-
Mitogen-activated protein kinase
- GSK3β:
-
Glycogen synthase kinase 3 beta
- IDE:
-
Insulin degrading enzyme
- PP2A:
-
Protein phosphatase 2A
- WAT:
-
White adipose tissue
- NFTs:
-
Neurofibrillary tangles
- ACH:
-
Amyloid cascade hypothesis
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GK visualized the presented idea and contributed to the manuscript writing. SK contributed to literature searches and the preparation of the manuscript. HB and HT supervised and contributed to the final manuscript approval. GK revised and approved the manuscript. The authors confirm that no paper mill and artificial intelligence was used.
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Kothawade, S.M., Buttar, H.S., Tuli, H.S. et al. Therapeutic potential of flavonoids in the management of obesity-induced Alzheimer’s disease: an overview of preclinical and clinical studies. Naunyn-Schmiedeberg's Arch Pharmacol 396, 2813–2830 (2023). https://doi.org/10.1007/s00210-023-02529-y
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DOI: https://doi.org/10.1007/s00210-023-02529-y