Neurotherapeutic Effects of Quercetin and Its Metabolite Compounds on Cognitive Impairment and Parkinson's Disease: An In Silico Study

by Selleckchem | Mar 22 2023

Background and objective: Little is known about the metabolomic profile of quercetin and its biological effects. This study aimed to determine the biological activities of quercetin and its metabolite products, as well as the molecular mechanisms of quercetin in cognitive impairment (CI) and Parkinson's disease (PD).

Methods: Key methods used were MetaTox, PASS Online, ADMETlab 2.0, SwissADME, CTD MicroRNA MIENTURNE, AutoDock, and Cytoscape.

Results: A total of 28 quercetin metabolite compounds were identified by phase I reactions (hydroxylation and hydrogenation reactions) and phase II reactions (methylation, O-glucuronidation, and O-sulfation reactions). Quercetin and its metabolites were found to inhibit cytochrome P450 (CYP) 1A, CYP1A1, and CYP1A2. The studied compounds demonstrated significant gastrointestinal absorption and satisfied Lipinsky's criterion. Due to their high blood-brain barrier permeability, P-glycoprotein inhibition, anticancer, anti-inflammatory, and antioxidant capabilities, quercetin and its metabolite products have been proposed as promising molecular targets for the therapy of CI and PD. By regulating the expression of crucial signaling pathways [mitogen-activated protein kinase (MAPK) signaling pathway, and neuroinflammation and glutamatergic signaling], genes [brain derived neurotrophic factor (BDNF), human insulin gene (INS), and dopamine receptor D2 (DRD2), miRNAs (hsa-miR-16-5p, hsa-miR-26b-5p, hsa-miR-30a-5p, hsa-miR-125b-5p, hsa-miR-203a-3p, and hsa-miR-335-5p], and transcription factors [specificity protein 1 (SP1), v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA), and nuclear factor Kappa B subunit 1 (NFKB1)], quercetin exhibited its neurotherapeutic effects in CI and PD. In addition to inhibiting β-N-acetylhexosaminidase, quercetin also showed robust interactions and binding affinities with heme oxygenase 1 (HMOX1), superoxide dismutase 2 (SOD2), tumor necrosis factor (TNF), nitric oxide synthase 2 (NOS2), brain-derived neurotrophic factor (BDNF), INS, DRD2, and γ-aminobutyric acid type A (GABAa).

Conclusion: This study identified 28 quercetin metabolite products. The metabolites have similar characteristics to quercetin such as physicochemical properties, absorption, distribution, metabolism, and excretion (ADME), and biological activities. More research, especially clinical trials, is needed to find out how quercetin and its metabolites protect against CI and PD.

Comments：

Overall, this study provides valuable insights into the metabolomic profile and biological activities of quercetin and its metabolite products in relation to cognitive impairment and Parkinson's disease. The study suggests that quercetin and its metabolites have promising therapeutic potential due to their ability to regulate crucial signaling pathways, genes, miRNAs, and transcription factors. The study also suggests that quercetin and its metabolites possess robust interactions and binding affinities with key proteins involved in neuroprotection, such as HMOX1, SOD2, and BDNF.

However, it is important to note that the findings of this study are based on in silico and in vitro experiments and further research is needed to confirm the potential therapeutic effects of quercetin and its metabolites in vivo and in human clinical trials. Additionally, the study did not address potential adverse effects or toxicity of quercetin and its metabolites, which should also be investigated in future research.