Network Pharmacology Integrated With Quantum‐Polarized Ligand Docking and Molecular Simulation Revealed the Anti‐Diabetic Potential of Curcumin

<p dir="ltr">Diabetes mellitus is a chronic metabolic disorder affecting millions of people worldwide and causes serious complications such as diabetic nephropathy. Curcumin, a natural polyphenol derived from turmeric, has demonstrated antidiabetic, anti‐inflammatory, and antioxidant...

وصف كامل

محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Abbas Khan (5141000) (author)
مؤلفون آخرون: Abrar Mohammad Sayaf (11644294) (author), AbdalRahman Alshammarri (22391983) (author), Muhammad Ammar Zahid (18123775) (author), Raed M. Al‐Zoubi (21348629) (author), Mohanad Shkoor (3768385) (author), Tarek Benameur (196206) (author), Dong‐Qing Wei (22330774) (author), Abdelali Agouni (181926) (author)
منشور في: 2024
الموضوعات:
الوسوم: إضافة وسم
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author Abbas Khan (5141000)
author2 Abrar Mohammad Sayaf (11644294)
AbdalRahman Alshammarri (22391983)
Muhammad Ammar Zahid (18123775)
Raed M. Al‐Zoubi (21348629)
Mohanad Shkoor (3768385)
Tarek Benameur (196206)
Dong‐Qing Wei (22330774)
Abdelali Agouni (181926)
author2_role author
author
author
author
author
author
author
author
author_facet Abbas Khan (5141000)
Abrar Mohammad Sayaf (11644294)
AbdalRahman Alshammarri (22391983)
Muhammad Ammar Zahid (18123775)
Raed M. Al‐Zoubi (21348629)
Mohanad Shkoor (3768385)
Tarek Benameur (196206)
Dong‐Qing Wei (22330774)
Abdelali Agouni (181926)
author_role author
dc.creator.none.fl_str_mv Abbas Khan (5141000)
Abrar Mohammad Sayaf (11644294)
AbdalRahman Alshammarri (22391983)
Muhammad Ammar Zahid (18123775)
Raed M. Al‐Zoubi (21348629)
Mohanad Shkoor (3768385)
Tarek Benameur (196206)
Dong‐Qing Wei (22330774)
Abdelali Agouni (181926)
dc.date.none.fl_str_mv 2024-09-30T09:00:00Z
dc.identifier.none.fl_str_mv 10.1002/slct.202402379
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Network_Pharmacology_Integrated_With_Quantum_Polarized_Ligand_Docking_and_Molecular_Simulation_Revealed_the_Anti_Diabetic_Potential_of_Curcumin/30305968
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biomedical and clinical sciences
Medical biochemistry and metabolomics
Pharmacology and pharmaceutical sciences
Diabetes mellitus
Curcumin
Metabolic disorder
Insulin resistance
Diabetic nephropathy
dc.title.none.fl_str_mv Network Pharmacology Integrated With Quantum‐Polarized Ligand Docking and Molecular Simulation Revealed the Anti‐Diabetic Potential of Curcumin
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <p dir="ltr">Diabetes mellitus is a chronic metabolic disorder affecting millions of people worldwide and causes serious complications such as diabetic nephropathy. Curcumin, a natural polyphenol derived from turmeric, has demonstrated antidiabetic, anti‐inflammatory, and antioxidant properties. However, the molecular mechanisms underlying curcumin's anti‐diabetic effects remain incompletely understood. This study employed network pharmacology, molecular docking, and simulation techniques to explore the potential targets, and key pathways of curcumin in the treatment of diabetes. Using SwissTarget prediction and Superpred databases, we predicted the molecular targets for curcumin, while diabetes‐associated genes were obtained from DisGeNet. We identified 60 common targets for curcumin in diabetes. Protein‐protein interaction (PPI) analysis revealed three sub‐networks and ten hub genes with AKT1, TNF‐α, EGFR, and STAT3 identified as key hub genes that could serve as potential biomarkers. Gene enrichment analysis indicated that these genes primarily regulate insulin resistance and other metabolic pathways. Quantum‐polarized ligand docking (QPLD) showed that curcumin establishes multiple hydrogen and hydrophobic interactions with the essential amino acids of these hub targets. Molecular simulation results demonstrated stable dynamic behavior, a compact structure, and variations in residue flexibility. Binding free energy calculations using MM/GBSA and MM/PBSA methods validate curcumin's strong binding to the potential targets. Total binding free energy using MM/GBSA ranged from −21.35 to −30.94 kcal/mol while MM/PBSA calculations showed total binding free energy values between −19.80 and −26.66 kcal/mol. Altogether, this study provides valuable insights into the molecular targets of curcumin in diabetes and lays the foundation for future advancements in diabetes treatment.</p><h2>Other Information</h2><p dir="ltr">Published in: ChemistrySelect<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1002/slct.202402379" target="_blank">https://dx.doi.org/10.1002/slct.202402379</a></p>
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identifier_str_mv 10.1002/slct.202402379
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/30305968
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spelling Network Pharmacology Integrated With Quantum‐Polarized Ligand Docking and Molecular Simulation Revealed the Anti‐Diabetic Potential of CurcuminAbbas Khan (5141000)Abrar Mohammad Sayaf (11644294)AbdalRahman Alshammarri (22391983)Muhammad Ammar Zahid (18123775)Raed M. Al‐Zoubi (21348629)Mohanad Shkoor (3768385)Tarek Benameur (196206)Dong‐Qing Wei (22330774)Abdelali Agouni (181926)Biomedical and clinical sciencesMedical biochemistry and metabolomicsPharmacology and pharmaceutical sciencesDiabetes mellitusCurcuminMetabolic disorderInsulin resistanceDiabetic nephropathy<p dir="ltr">Diabetes mellitus is a chronic metabolic disorder affecting millions of people worldwide and causes serious complications such as diabetic nephropathy. Curcumin, a natural polyphenol derived from turmeric, has demonstrated antidiabetic, anti‐inflammatory, and antioxidant properties. However, the molecular mechanisms underlying curcumin's anti‐diabetic effects remain incompletely understood. This study employed network pharmacology, molecular docking, and simulation techniques to explore the potential targets, and key pathways of curcumin in the treatment of diabetes. Using SwissTarget prediction and Superpred databases, we predicted the molecular targets for curcumin, while diabetes‐associated genes were obtained from DisGeNet. We identified 60 common targets for curcumin in diabetes. Protein‐protein interaction (PPI) analysis revealed three sub‐networks and ten hub genes with AKT1, TNF‐α, EGFR, and STAT3 identified as key hub genes that could serve as potential biomarkers. Gene enrichment analysis indicated that these genes primarily regulate insulin resistance and other metabolic pathways. Quantum‐polarized ligand docking (QPLD) showed that curcumin establishes multiple hydrogen and hydrophobic interactions with the essential amino acids of these hub targets. Molecular simulation results demonstrated stable dynamic behavior, a compact structure, and variations in residue flexibility. Binding free energy calculations using MM/GBSA and MM/PBSA methods validate curcumin's strong binding to the potential targets. Total binding free energy using MM/GBSA ranged from −21.35 to −30.94 kcal/mol while MM/PBSA calculations showed total binding free energy values between −19.80 and −26.66 kcal/mol. Altogether, this study provides valuable insights into the molecular targets of curcumin in diabetes and lays the foundation for future advancements in diabetes treatment.</p><h2>Other Information</h2><p dir="ltr">Published in: ChemistrySelect<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1002/slct.202402379" target="_blank">https://dx.doi.org/10.1002/slct.202402379</a></p>2024-09-30T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1002/slct.202402379https://figshare.com/articles/journal_contribution/Network_Pharmacology_Integrated_With_Quantum_Polarized_Ligand_Docking_and_Molecular_Simulation_Revealed_the_Anti_Diabetic_Potential_of_Curcumin/30305968CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/303059682024-09-30T09:00:00Z
spellingShingle Network Pharmacology Integrated With Quantum‐Polarized Ligand Docking and Molecular Simulation Revealed the Anti‐Diabetic Potential of Curcumin
Abbas Khan (5141000)
Biomedical and clinical sciences
Medical biochemistry and metabolomics
Pharmacology and pharmaceutical sciences
Diabetes mellitus
Curcumin
Metabolic disorder
Insulin resistance
Diabetic nephropathy
status_str publishedVersion
title Network Pharmacology Integrated With Quantum‐Polarized Ligand Docking and Molecular Simulation Revealed the Anti‐Diabetic Potential of Curcumin
title_full Network Pharmacology Integrated With Quantum‐Polarized Ligand Docking and Molecular Simulation Revealed the Anti‐Diabetic Potential of Curcumin
title_fullStr Network Pharmacology Integrated With Quantum‐Polarized Ligand Docking and Molecular Simulation Revealed the Anti‐Diabetic Potential of Curcumin
title_full_unstemmed Network Pharmacology Integrated With Quantum‐Polarized Ligand Docking and Molecular Simulation Revealed the Anti‐Diabetic Potential of Curcumin
title_short Network Pharmacology Integrated With Quantum‐Polarized Ligand Docking and Molecular Simulation Revealed the Anti‐Diabetic Potential of Curcumin
title_sort Network Pharmacology Integrated With Quantum‐Polarized Ligand Docking and Molecular Simulation Revealed the Anti‐Diabetic Potential of Curcumin
topic Biomedical and clinical sciences
Medical biochemistry and metabolomics
Pharmacology and pharmaceutical sciences
Diabetes mellitus
Curcumin
Metabolic disorder
Insulin resistance
Diabetic nephropathy