Unravelling the Molecular Mechanisms of a Quercetin Nanocrystal for Treating Potential Parkinson’s Disease in a Rotenone Model: Supporting Evidence of Network Pharmacology and In Silico Data Analysis
The prevalence of Parkinson’s disease places a significant burden on society; therefore, there is an urgent need to develop more effective drugs. However, the development of these drugs is both expensive and risky. Quercetin (QUE) has potent pharmacological effects on neurodegenerative diseases, but...
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MDPI AG
2023-10-01
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| author | Yeruva Sai Lakshmi D. S. N. B. K. Prasanth Karumuri Taraka Sunil Kumar Sheikh F. Ahmad Seemaladinne Ramanjaneyulu Nalluri Rahul Praveen Kumar Pasala |
| author_facet | Yeruva Sai Lakshmi D. S. N. B. K. Prasanth Karumuri Taraka Sunil Kumar Sheikh F. Ahmad Seemaladinne Ramanjaneyulu Nalluri Rahul Praveen Kumar Pasala |
| author_sort | Yeruva Sai Lakshmi |
| collection | DOAJ |
| description | The prevalence of Parkinson’s disease places a significant burden on society; therefore, there is an urgent need to develop more effective drugs. However, the development of these drugs is both expensive and risky. Quercetin (QUE) has potent pharmacological effects on neurodegenerative diseases, but its low solubility in water and poor bioavailability limit its use in pharmaceutical applications. In this study, Quercetin nanocrystals (QNC) were synthesized and compared to standard QUE. A network-pharmacology-based methodology was applied, including target prediction, network construction, a gene ontology (GO) analysis, a KEGG pathway enrichment analysis, and molecular docking. This study aimed to identify the targets of QUE relevant to the treatment of Parkinson’s disease and investigate the associated pharmacological mechanisms. Most of the predicted targets are involved in dopamine uptake during synaptic transmission. QUE regulates the key targets DRD2 and DRD4, which significantly affect dopaminergic synapses. The molecular docking results showed that QUE had a better binding affinity than the standard drug l-Dopa. From these experiments, it can be concluded that QNC effectively reduced the adverse effects caused by rotenone-induced oxidative stress in biochemical, neurochemical, and histopathological alterations. Therefore, QNC can potentially treat Parkinson’s disease, and its effectiveness should be assessed in future clinical trials. |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T21:24:34Z |
| publishDate | 2023-10-01 |
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| series | Biomedicines |
| spelling | doaj.art-7d8b38dad47947b1a97f0f6e9d1c37b12023-11-19T15:46:39ZengMDPI AGBiomedicines2227-90592023-10-011110275610.3390/biomedicines11102756Unravelling the Molecular Mechanisms of a Quercetin Nanocrystal for Treating Potential Parkinson’s Disease in a Rotenone Model: Supporting Evidence of Network Pharmacology and In Silico Data AnalysisYeruva Sai Lakshmi0D. S. N. B. K. Prasanth1Karumuri Taraka Sunil Kumar2Sheikh F. Ahmad3Seemaladinne Ramanjaneyulu4Nalluri Rahul5Praveen Kumar Pasala6Department of Pharmacology, Santhiram College of Pharmacy, JNTUA, Nandyal 518112, Andhra Pradesh, IndiaDepartment of Pharmacognosy, KVSR Siddhartha College of Pharmaceutical Sciences, Vijayawada 520010, Andhra Pradesh, IndiaDepartment of Pharmaceutics, Shri Vishu College of Pharmacy, Bhimavaram 534202, Andhra Pradesh, IndiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Chemistry and Biochemistry, Lamar University, Beaumont, TX 77705, USAIndependent Researcher, Kingsville, TX 78363, USADepartment of Pharmacology, Raghavendra Institute of Pharmaceutical Education and Research, JNTUA, Anantapuramu 515721, Andhra Pradesh, IndiaThe prevalence of Parkinson’s disease places a significant burden on society; therefore, there is an urgent need to develop more effective drugs. However, the development of these drugs is both expensive and risky. Quercetin (QUE) has potent pharmacological effects on neurodegenerative diseases, but its low solubility in water and poor bioavailability limit its use in pharmaceutical applications. In this study, Quercetin nanocrystals (QNC) were synthesized and compared to standard QUE. A network-pharmacology-based methodology was applied, including target prediction, network construction, a gene ontology (GO) analysis, a KEGG pathway enrichment analysis, and molecular docking. This study aimed to identify the targets of QUE relevant to the treatment of Parkinson’s disease and investigate the associated pharmacological mechanisms. Most of the predicted targets are involved in dopamine uptake during synaptic transmission. QUE regulates the key targets DRD2 and DRD4, which significantly affect dopaminergic synapses. The molecular docking results showed that QUE had a better binding affinity than the standard drug l-Dopa. From these experiments, it can be concluded that QNC effectively reduced the adverse effects caused by rotenone-induced oxidative stress in biochemical, neurochemical, and histopathological alterations. Therefore, QNC can potentially treat Parkinson’s disease, and its effectiveness should be assessed in future clinical trials.https://www.mdpi.com/2227-9059/11/10/2756Parkinson’s diseaserotenonequercetin nanocrystals (QNC)antioxidant system |
| spellingShingle | Yeruva Sai Lakshmi D. S. N. B. K. Prasanth Karumuri Taraka Sunil Kumar Sheikh F. Ahmad Seemaladinne Ramanjaneyulu Nalluri Rahul Praveen Kumar Pasala Unravelling the Molecular Mechanisms of a Quercetin Nanocrystal for Treating Potential Parkinson’s Disease in a Rotenone Model: Supporting Evidence of Network Pharmacology and In Silico Data Analysis Biomedicines Parkinson’s disease rotenone quercetin nanocrystals (QNC) antioxidant system |
| title | Unravelling the Molecular Mechanisms of a Quercetin Nanocrystal for Treating Potential Parkinson’s Disease in a Rotenone Model: Supporting Evidence of Network Pharmacology and In Silico Data Analysis |
| title_full | Unravelling the Molecular Mechanisms of a Quercetin Nanocrystal for Treating Potential Parkinson’s Disease in a Rotenone Model: Supporting Evidence of Network Pharmacology and In Silico Data Analysis |
| title_fullStr | Unravelling the Molecular Mechanisms of a Quercetin Nanocrystal for Treating Potential Parkinson’s Disease in a Rotenone Model: Supporting Evidence of Network Pharmacology and In Silico Data Analysis |
| title_full_unstemmed | Unravelling the Molecular Mechanisms of a Quercetin Nanocrystal for Treating Potential Parkinson’s Disease in a Rotenone Model: Supporting Evidence of Network Pharmacology and In Silico Data Analysis |
| title_short | Unravelling the Molecular Mechanisms of a Quercetin Nanocrystal for Treating Potential Parkinson’s Disease in a Rotenone Model: Supporting Evidence of Network Pharmacology and In Silico Data Analysis |
| title_sort | unravelling the molecular mechanisms of a quercetin nanocrystal for treating potential parkinson s disease in a rotenone model supporting evidence of network pharmacology and in silico data analysis |
| topic | Parkinson’s disease rotenone quercetin nanocrystals (QNC) antioxidant system |
| url | https://www.mdpi.com/2227-9059/11/10/2756 |
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