LC-HRMS metabolomics, isolation, network pharmacology, and molecular docking based evaluation of anti-cancer potential of compounds of Glycyrrhiza glabra L.

Abstract

Network pharmacology plays a crucial role in drug discovery by identifying target genes and elucidating underlying mechanisms. In the present work, Glycyrrhiza glabra hydroalcoholic extract (GGHE) was subjected to LC-MS phytochemical profiling, followed by in-silico ADME analysis of identified compounds. Various databases like GeneCards, SEA databases, PharmMapper, DisGeNet, SwissTargetPrediction, and STRING were used to find information on target genes, and a network was created using CytoScape. The combination synergy study was done by constructing hierarchical networks. In the LC-MS study, 16 compounds were identified, with 12 passing ADME screening. Enrichment analysis revealed the involvement of various pathways linked to cancer, including EGFR TKI resistance, MAPK, PD-L1/PD-1, proteoglycans, PI3K-Akt, ErbB, and RAS pathways. Synergy studies highlighted mTOR and CHUK gene targets for two compounds. Besides, secondary metabolites were isolated using chromatographic techniques, characterized by NMR, and evaluated for cytotoxicity in human cancer cell lines by MTT assay. Six compounds viz hispaglabridin A, glabrol, isoliquiritin apioside, formononetin, glycyrrhizin, and glabridin were isolated, and most of these were subjected to cytotoxic evaluation. Glabridin showed the highest potency against breast cancer cell lines (MDA-MB-231 and MCF-7) and Network pharmacology suggests Glabrene and Glyinflanin A possesses anti-cancer potential. Thus, the study demonstrates GGHE or its compounds have potential against breast, prostate, and pancreatic cancer.