The Therapeutic Potential of Quercetin in Parkinson’s Disease: Insights into its Molecular and Cellular Regulation

Abstract

Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disorder characterized by the progressive death of dopaminergic neurons in the substantia nigra pars compacta (SNc). PD is a multifactorial disorder, with several different factors being suggested to play a synergistic pathophysiological role, including oxidative stress, autophagy, underlying pro-inflammatory events and neurotransmitters abnormalities. Overall, PD can be viewed as the product of a complex interaction of environmental factors acting on a given genetic background. The importance of this subject has gained more attention to discover novel therapies to prevent as well as treat PD. According to previous research, drugs used to treat PD have indicated significant limitations. Therefore, the role of flavonoids has been extensively studied in PD treatment. Quercetin, a plant flavonol from the flavonoid group, has been considered as a supplemental therapy for PD. Quercetin has pharmacological functions in PD by controlling different molecular pathways. Although few studies intended to evaluate the basis for the use of quercetin in the context of PD have been conducted so far, at present, there is very little evidence available addressing the underlying mechanisms of action. Various principal aspects of these treatment procedures remain unknown. Here, currently existing knowledge supporting the use of quercetin for the clinical management of PD has been reviewed.

Compound Dihuang Granule Inhibits Nigrostriatal Pathway Apoptosis in Parkinson’s Disease by Suppressing the JNK/AP-1 Pathway

“…Miq. ex Havil, has been reported to ameliorate motor deficits, protect against DA neurodegeneration, and reduce 6-OHDA-induced neurotoxicity and to be an anti-inflammatory agent (Ay et al, 2017;Tamtaji et al, 2020). Tanshinone IIA, a major component of Salvia miltiorrhiza Bge, has been shown to elevate TH protein levels and suppress caspase-3 expression in SNpc, thereby protecting DA neurons (Tian et al, 2018).…”

Control of Reactive Oxygen Species for the Prevention of Parkinson’s Disease: The Possible Application of Flavonoids

“…For these reasons, flavonoids, having potent free radical scavenging activity, have been considered and investigated as dietary supplements that prevent and suppress the PD pathogenesis. So, it has been studied whether the risk of PD pathogenesis can be decreased by a diet with flavonoids, such as fisetin, quercetin, naringin, baicalein, and genistein ( Table 3 ) [ 31 , 41 , 122 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 ].…”

“…Nrf2 acts downstream of multiple cellular signaling pathways, which are associated with antioxidant pathway, heme/iron pathway, glutathione pathway, thioredoxin activity, iron/copper/zinc regulation, and intracellular protein accumulation regulation [ 158 ]. Flavonoids activate Nrf2 by phosphorylating via ERK1/2, JNK, PI3K/Akt/mTOR, and p38 MAPK signaling pathway [ 43 , 133 , 159 , 160 , 161 ]. Phosphorylated Nrf2 is dissociated with Kelch-like ECH-associated protein 1 (Keap1) and translocated into the nucleus inducing expression of anti-oxidative and anti-inflammatory factors [ 43 , 133 ].…”

“…Flavonoids activate Nrf2 by phosphorylating via ERK1/2, JNK, PI3K/Akt/mTOR, and p38 MAPK signaling pathway [ 43 , 133 , 159 , 160 , 161 ]. Phosphorylated Nrf2 is dissociated with Kelch-like ECH-associated protein 1 (Keap1) and translocated into the nucleus inducing expression of anti-oxidative and anti-inflammatory factors [ 43 , 133 ]. Simultaneously, Keap1 inhibits the translocation of a nuclear factor kappa-light-chain-enhancer of activated B cells (NF- Κ B) from cytoplasm to nucleus, resulting in the downregulation of gene expression for pro-inflammatory cytokines, such as TNF-α and IL-1β [ 43 , 86 , 160 ].…”

“…Flavonols: Flavonols, including quercetin, myricetin, fisetin, rutin, and kaempferol, have been investigated as neuroprotective agents against neurodegenerative diseases such as AD and PD. They exhibit anti-oxidative and anti-inflammatory effects via cellular signaling pathways, such as ERK1/2, Akt, GSK-3β, and JNK, and it has been revealed that these flavonols can protect DA neurons in vivo and in vitro ( Table 3 ) [ 45 , 122 , 132 , 133 , 185 , 186 ].…”