The Use of Nanocarriers to Enhance the Anti-neuroinflammatory Potential of Dietary Flavonoids in Animal Models of Neurodegenerative Diseases: A Systematic Review

Background: Neurodegenerative diseases (NDs) have become a common and growing cause of mortality and morbidity worldwide, especially in older adults. The natural flavonoids found in fruits and vegetables have been shown to have therapeutic effects against many diseases, including NDs; however, in general, flavonoids have limited bioavailability to the target cells. One promising strategy to increase bioavailability is to entrap them in nanocarriers. Objective: This article aims to review the potential role of nanocarriers in enhancing the antineuroinflammatory efficacy of flavonoids in experimentally induced ND. Methods: A literature search was conducted in the scientific databases using the keywords “neurodegenerative”, “anti-neuroinflammatory”, “dietary flavonoids,” “nanoparticles”, and “therapeutic mechanisms”. Results: A total of 289 articles were initially identified, of which 45 articles reported on flavonoids. After completion of the selection process, five articles that met the criteria of the review were selected for analysis. Preclinical studies identified in this review showed that nanoencapsulated flavonoids attenuated cognitive impairment and seizure, improved behavioral patterns, and reduced levels of astrocytes. Importantly, they exhibited strong antioxidant properties, increasing the levels of antioxidant enzymes and reducing oxidative stress (OS) biomarkers. Moreover, nanocarrier-complexed flavonoids decreased the levels of the pro-inflammatory cytokines, interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α), by inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ΚB) and nod-like receptor protein 3 inflammasome activation (NLRP3). They also had remarkable effects on important ND-related neurotransmitters, improved cognitive function via cholinergic neurotransmission, and increased prefrontal cortical and hippocampal norepinephrine (NE) and 5-hydroxytryptamine (5-HT). Conclusion: Nanoencapsulated flavonoids should, therefore, be considered a novel therapeutic approach for the treatment of NDs.