In silico and In vitro profiling of lariciresinol against PLA2: A molecular approach to regulate inflammation
Chronic inflammation underlies various diseases, including cardiovascular disorders, cancer, and autoimmune conditions. Phospholipase A2 (PLA2) plays a central role in the inflammatory response by hydrolyzing membrane phospholipids to release arachidonic acid, a precursor for pro-inflammatory eicosa...
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| Format: | Article |
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Elsevier
2025-12-01
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| Series: | European Journal of Medicinal Chemistry Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772417425000469 |
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| author | Fathimath Henna G. Arun Kumar Amritha Thaikkad T.K. Varun E. Jayadevi Variyar Rajesh Raju J. Abhithaj |
| author_facet | Fathimath Henna G. Arun Kumar Amritha Thaikkad T.K. Varun E. Jayadevi Variyar Rajesh Raju J. Abhithaj |
| author_sort | Fathimath Henna |
| collection | DOAJ |
| description | Chronic inflammation underlies various diseases, including cardiovascular disorders, cancer, and autoimmune conditions. Phospholipase A2 (PLA2) plays a central role in the inflammatory response by hydrolyzing membrane phospholipids to release arachidonic acid, a precursor for pro-inflammatory eicosanoids via the COX and LOX pathways. Due to its upstream regulatory function, PLA2 presents a strategic target for inflammation control. However, developing safe and effective PLA2 inhibitors remains challenging due to limitations in efficacy and side effects.Natural compounds, particularly phytochemicals with anti-inflammatory potential, are gaining attention as alternative therapeutics. This study investigated Lariciresinol, a phenolic lignan from Zingiber officinale (ginger), for its inhibitory activity against PLA2. Selected through in silico screening, Lariciresinol was evaluated using molecular docking, molecular dynamics (MD) simulations, and in vitro enzyme inhibition assays. The compound showed competitive inhibition with an IC50 of 57.6μM. The binding energy of Lariciresinol improved from −24.71kcal/mol to −34.38kcal/mol after MD simulations. The results from the binding energy analysis and MD simulations revealed stable interactions with key catalytic residues, supporting its proposed mechanism of action.Further in silico analysis of Root Mean Square Deviation, Root Mean Square Fluctuation, Radius of Gyration, H-bonds, Solvent Accessible Surface Area, and Free Energy Landscape validated the results. These results highlight Lariciresinol a promising scaffold for developing novel PLA2-targeted anti-inflammatory agents, warranting further in vitro and in vivo validation for clinical application. |
| format | Article |
| id | doaj-art-e330dd9fd6434704ab1f2af05957023f |
| institution | DOAJ |
| issn | 2772-4174 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | European Journal of Medicinal Chemistry Reports |
| spelling | doaj-art-e330dd9fd6434704ab1f2af05957023f2025-08-20T03:16:10ZengElsevierEuropean Journal of Medicinal Chemistry Reports2772-41742025-12-011510029010.1016/j.ejmcr.2025.100290In silico and In vitro profiling of lariciresinol against PLA2: A molecular approach to regulate inflammationFathimath Henna0G. Arun Kumar1Amritha Thaikkad2T.K. Varun3E. Jayadevi Variyar4Rajesh Raju5J. Abhithaj6Centre for Integrative Omics Data Science, Yenepoya (Deemed to Be University), Mangalore, Karnataka, (575018), IndiaDepartment of Molecular Biology, Kannur University, Kannur, Kerala, 670661, IndiaCentre for Integrative Omics Data Science, Yenepoya (Deemed to Be University), Mangalore, Karnataka, (575018), IndiaCentre for Integrative Omics Data Science, Yenepoya (Deemed to Be University), Mangalore, Karnataka, (575018), IndiaDepartment of Biotechnology & Microbiology Kannur University, Kannur, Kerala, 670661, IndiaCentre for Integrative Omics Data Science, Yenepoya (Deemed to Be University), Mangalore, Karnataka, (575018), India; Corresponding author.Centre for Integrative Omics Data Science, Yenepoya (Deemed to Be University), Mangalore, Karnataka, (575018), India; Corresponding author.Chronic inflammation underlies various diseases, including cardiovascular disorders, cancer, and autoimmune conditions. Phospholipase A2 (PLA2) plays a central role in the inflammatory response by hydrolyzing membrane phospholipids to release arachidonic acid, a precursor for pro-inflammatory eicosanoids via the COX and LOX pathways. Due to its upstream regulatory function, PLA2 presents a strategic target for inflammation control. However, developing safe and effective PLA2 inhibitors remains challenging due to limitations in efficacy and side effects.Natural compounds, particularly phytochemicals with anti-inflammatory potential, are gaining attention as alternative therapeutics. This study investigated Lariciresinol, a phenolic lignan from Zingiber officinale (ginger), for its inhibitory activity against PLA2. Selected through in silico screening, Lariciresinol was evaluated using molecular docking, molecular dynamics (MD) simulations, and in vitro enzyme inhibition assays. The compound showed competitive inhibition with an IC50 of 57.6μM. The binding energy of Lariciresinol improved from −24.71kcal/mol to −34.38kcal/mol after MD simulations. The results from the binding energy analysis and MD simulations revealed stable interactions with key catalytic residues, supporting its proposed mechanism of action.Further in silico analysis of Root Mean Square Deviation, Root Mean Square Fluctuation, Radius of Gyration, H-bonds, Solvent Accessible Surface Area, and Free Energy Landscape validated the results. These results highlight Lariciresinol a promising scaffold for developing novel PLA2-targeted anti-inflammatory agents, warranting further in vitro and in vivo validation for clinical application.http://www.sciencedirect.com/science/article/pii/S2772417425000469PLA2Molecular dockingMolecular dynamicsLariciresinolInflammationAlternative therapeutic |
| spellingShingle | Fathimath Henna G. Arun Kumar Amritha Thaikkad T.K. Varun E. Jayadevi Variyar Rajesh Raju J. Abhithaj In silico and In vitro profiling of lariciresinol against PLA2: A molecular approach to regulate inflammation European Journal of Medicinal Chemistry Reports PLA2 Molecular docking Molecular dynamics Lariciresinol Inflammation Alternative therapeutic |
| title | In silico and In vitro profiling of lariciresinol against PLA2: A molecular approach to regulate inflammation |
| title_full | In silico and In vitro profiling of lariciresinol against PLA2: A molecular approach to regulate inflammation |
| title_fullStr | In silico and In vitro profiling of lariciresinol against PLA2: A molecular approach to regulate inflammation |
| title_full_unstemmed | In silico and In vitro profiling of lariciresinol against PLA2: A molecular approach to regulate inflammation |
| title_short | In silico and In vitro profiling of lariciresinol against PLA2: A molecular approach to regulate inflammation |
| title_sort | in silico and in vitro profiling of lariciresinol against pla2 a molecular approach to regulate inflammation |
| topic | PLA2 Molecular docking Molecular dynamics Lariciresinol Inflammation Alternative therapeutic |
| url | http://www.sciencedirect.com/science/article/pii/S2772417425000469 |
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