Network pharmacology and bioinformatics based investigation of Phyllanthus fraternus: herb-drug interaction study

Abstract

Phyllanthus fraternus (PF), a plant from the Euphorbiaceae family, is used extensively in ayurvedic formulations for its significant medicinal properties. When PF is administered alongside conventional drugs, there could be potential herb-drug interactions between the active compounds and the genes involved in drug transport and metabolism. Hence, this study was designed to investigate potential herb-drug interactions, focusing on elucidating their functional and pharmacological mechanisms, using an integrated approach of metabolite profiling and network pharmacology. We utilized LC-MS to generate metabolite profiling of PF and network pharmacology for predicting key targets and pathways. This comprehensive analysis involved the construction of networks illustrating the relationships among compounds, targets, and pathways and the exploration of protein-protein interactions and protein-ligand interactions. In this study, a total of 79 compounds were identified in LC-MS, such as alkaloids, steroids, saponins, flavonoids, lignans, phenolic acids, tannins, terpenoids, and fatty acids. The identified compound’s physicochemical properties were predicted using SwissADME. Network analysis predicted 1076 PF-related genes and 1497 genes associated with drug transport and metabolism, identifying 417 overlapping genes, including 51 related to drug transport and metabolism. Based on the degree of interaction the hub targets like ABCB1, CYP1A1, CYP1A2, CYP2C9, and CYP3A4 were identified. In the compound-target-pathway network, 2,4-bis(1,1-dimethyl ethyl)-phenol; 5-Methoxy-N-[(5-Methylpyridin-2-yl) sulfonyl]-1h-Indole-2-Carboxamide; and E,E,Z-1,3,12-Nonadecatriene-5,14-diol possessed more interactions with the targets. This study helps identify bioactive compounds, essential targets, and pathways potentially implicated in these interactions, laying the foundation for future studies (in vitro and in vivo) to verify their potential to explore their clinical implications.Communicated by Ramaswamy H. Sarma