Employing multi-omics, pharmacoinformatics, and in vitro approaches to discover functional biomolecules in oyster mushroom flour

Abstract Oyster mushroom ( Pleurotus ostreatus ) is recognized as a functional food due to its bioactive compounds content which have therapeutic potential, particularly in metabolic disorder management. This study aims to explore the bioactive profile of oyster mushroom flour (OMF) using a multi-omics approach to evaluate its antioxidant, antiobesity, and antidiabetic properties. A comprehensive multi-omics approach has been employed, integrating metabolomics and proteomics profiling using LC-HRMS and Orbitrap mass spectrometry. In vitro assays assessed antioxidant capacity through ABTS and superoxide dismutase (SOD) activity, antiobesity potential via lipase inhibition and 3T3-L1 adipocyte assays, and antidiabetic effects via α-glucosidase, α-amylase, and dipeptidyl peptidase-4 (DPP-4) inhibition tests. In silico analysis further mapped molecular interactions and pathways. Metabolomic profiling identified 376 unique compounds and 13 peptides, including antioxidants, and enzyme inhibitors, contributing to antiobesity and antidiabetic effects. Proteomic analysis revealed peptides targeting metabolic pathways associated with oxidative stress and glucose regulation. γ-tocotrienol, estriol, kynurenic acid, and palmitoylcarnitine exhibited strong binding affinities with key metabolic targets, suggesting their potential as natural inhibitors for diabetes and obesity management. In vitro assays confirmed the oyster mushroom radical scavenging activity, lipase inhibition, and enzymatic modulation capabilities, with strong support from in silico analyses mapping molecular targets and pathways. These findings suggest P. ostreatus as a natural resource for managing metabolic disorders and developing evidence-based functional foods. This research bridges the gap between compound discovery and therapeutic application, paving the way for its broader utilization in nutraceuticals and precision nutrition strategies.