Unveiling the Potential of Flavonoids in the Regulation of Parkinson's Disease: Special Focus on Quercetin.

Parkinson's disease (PD) is an idiopathic and age-related neurodegenerative disorder, marked by the selective loss of dopaminergic neurons in the SNpc and the formation of α-synuclein aggregates. Consequently, this leads to motor and non-motor complications in PD-like patients. Research on plant-based secondary metabolites, such as polyphenols, confirmed that they may slow the development and progression of PD. Flavonoids generated the peak of interest due to their medicinal properties, including mitigation of the risk of PD. Quercetin, a subclass of flavonol type of flavonoids, attracted attention as a potential neuroprotective agent. Quercetin has been demonstrated to have anti-oxidant, anti-inflammatory, anti-apoptotic, and neuroprotective properties, along with obstruction of α-synuclein accumulation and mitochondrial protection. Moreover, studies also revealed that quercetin ameliorates the striatal dopamine content and distinctly modulates the various signalling pathways, including PI3K/AKT, Nrf2, MAPK and NF-kB that are involved in the disruption of disease. Further, quercetin modulates oxidative stress through upregulation of anti-oxidant enzymes, inhibits neuroinflammation via suppression of pro-inflammatory cytokines, prevents Lewy bodies formation and regulates autophagy along with apoptosis. By exhibiting the aforementioned effects, quercetin protects against the neuronal toxicity induced by various neurotoxins through multiple mechanisms to improve motor and non-motor functions. This highlights quercetin as a potential multifaceted therapeutic candidate for PD intervention. We searched for the published data on quercetin related to PD and summarized them in the current review. This review aims to address the understanding of mechanisms, therapeutic effects of quercetin and various models using neurotoxins to induce PD. This review aims to elucidate the underlying cellular and molecular mechanisms and therapeutic effects of quercetin, as well as to explore the various neurotoxin-induced models of PD used to investigate its efficacy. The major part of this review article discusses the roles of quercetin in the management of PD in animals of several experimental models used by many research studies. Overall, quercetin represents a promising, safe, effective and potentially neuroprotective candidate for disease disease-modifying strategy to combat neurological disorders such as PD.