Phytomedicine Plus (Aug 2024)
Network pharmacology and molecular docking approach to elucidate potential phytocompounds, targets, and mechanisms of Glycyrrhiza glabra in the alleviation of cellular senescence
Abstract
Background: There is an increasing interest in identifying modulators of cellular senescence as potential anti-ageing agents. Nutritional modulation of senescence is pragmatic and medicinal plants are attractive sources of anti-cellular senescence drug candidates. Glycyrrhiza glabra (GG) is an extensively utilized medicinal plant and its anti-ageing and anti-cellular senescence effects are also known. The current study attempted to understand the anti-cellular senescence targets of GG components and their underlying pathways using network pharmacology and its validation through in silico molecular docking. Methods: Components of GG were screened using Dr. Duke's Phytochemical and Ethnobotanical Database and KNApSAcK database, target prediction was done using SuperPred 3.0, followed by mapping with cellular senescence gene targets obtained from GeneCards and CellAge databases. The STRING database and Cytoscape software were utilized for protein-protein and protein-target interaction analyses and further screening of core targets. GO and KEGG enrichment analysis was performed, and the top identified targets were subject to binding affinity evaluation with major GG compounds using molecular docking. Results: The 40 screened GG compounds overlapped with 71 potential gene targets of cellular senescence. PPI interaction analysis revealed top core targets as HIF1A, HSP90AB1, NF-κB1, STAT1, and HDAC2 while GO enrichment analysis showed protein phosphorylation and protein folding to be the top targeted biological processes. KEGG analysis revealed ‘pathways in cancer’ and ‘MAPK signalling pathway’ as top enriched pathways with several major classical regulators of cellular senescence that were targeted by GG. 4′-O-methylglabridin and glycyrrhisoflavanone categorically appeared to be the most potent interacting GG components with average binding affinity < 7.0 kcal/mol. Molecular docking revealed very strong binding affinities (< 7.0 kcal/mol) with HSP90AB1, CDK2, NFE2L2, and HIF1A. Conclusion: Together, our research paves the way for subsequent experimental verification of novel anti-cellular senescence components of GG that could be useful for developing GG-based herbal anti-ageing approaches.
