UHPLC-based phytochemical profiling and network pharmacology insights into mint-derived selenium nanoparticles

The convergence of nanotechnology with bioinformatics and the study of plant secondary metabolites hold remarkable potential for transformative scientific breakthroughs. Synergy enables a deeper understanding of the biosynthesis and functions of plant secondary metabolites, unlocking avenues to engineer novel applications in areas like pharmaceuticals, agriculture and sustainable materials. The present study was conducted to check the effect of mint extracts and mint-based selenium nanoparticles to improve the oxidative stress and evaluate the hub targets from plant metabolites for the management of diabetes. Two different species of Mentha (i.e., Mentha royleana and Mentha longifolia) and mint-based selenium nanoparticles were used with the concentrations ranging from 32.5 to 500 μg/mL. On the basis of in vitro antioxidant data, M. royleana showed the best inhibition (i.e., 79.28 %) and IC₅₀ values. For comparison, the standard positive drug (i.e., ascorbic acid) showed 82.8 % inhibition for DPPH, 73.29 % for ABTS, 69.47 % for reducing power, 75.9 % for phosphomolybdate and 68 % for hydrogen peroxide assays. Low IC₅₀ values of 156.33 ± 6.72 μg/mL and 215.85 ± 4.63 μg/mL for DPPH and RPA, respectively, were found in M. royleana based SeNPs, while for ABTS and H₂O₂, IC₅₀ values of 211.37 ± 2.86 μg/mL and 252.83 ± 2.88 μg/mL were found in M. longifolia plant extract. Furthermore, UHPLC-MS analysis of metabolites was carried out and compounds were identified on the basis of m/z score, literature survey and NIST db. All 146 identified compounds were further subjected for screening where their physicochemical properties, bioavailability score, drug-likeness score and cytotoxicity analysis were checked. The best 8 differentially expressed bioactive metabolites were used for SwissTargetPrediction, gene ontology enrichment analysis, KEGG pathways and Cytoscape analysis to determine their gene target, cell target, drug target and disease targets. Hub biotargets of Mentha were screened by Cytoscape analysis namely, TNF, ALB, PTGS2, STAT3, CASP3, ESR1, EGFR, MAPK1, ERBB2 and MAPK14, with highest degree/score. This indicates that these core genes have potent pharmacological effects against diabetes. Moreover, the analysis of KEGG pathways revealed that most metabolites had strong association with regulation of hormones, diabetes mellitus, TNF signaling pathways, insulin receptor signaling, Ras signaling pathways and regulation of cell cycle. Hence, the study revealed that Mentha extracts and selenium nanoparticles have the ability to improve ROS production and diabetes. The current data coupled with bioinformatics tools revealed great insights of the potential of these compounds in managing diabetes.