An integrative multi-omics approach to decipher the polypharmacological mechanism of okra (Abelmoschus esculentus) against type 2 diabetes mellitus

Abstract Type 2 diabetes mellitus (T2DM) is a complex polygenic metabolic disorder involving dysregulation of multiple genes and signaling pathways. Okra (Abelmoschus esculentus) has shown antidiabetic potential, although its molecular mechanisms remain inadequately understood. This study investigated the antidiabetic properties of okra using an integrative in silico approach. A total of 108 bioactive compounds were identified, with flavonoids as the predominant group. Transcriptomic analysis of the GSE21321 dataset identified 17 significantly dysregulated genes (DEGs) in T2DM patients. Gene Ontology and KEGG enrichment analyses revealed significant involvement in insulin signaling, PI3K/AKT, FoxO, and apoptosis-related pathways, highlighting the polygenic nature of T2DM. Compound-target interaction and network analyses identified key interactions between okra bioactives and diabetes-related proteins, including PTPN11, BCL2L1, INSR, and IGF1R. Molecular docking revealed predicted binding affinities, with quercetin showing the strongest interaction with IGF1R (-7.3 kcal/mol), suggesting its potential role in insulin signaling modulation. Organic acids, such as fumarate, malate, and citric acid, act as supportive modulators. ADME and toxicity predictions indicated favorable drug-likeness and generally low toxicity profiles. Overall, this study suggests that okra exerts antidiabetic effects through multi-target modulation of key molecular pathways, supporting its potential as a natural therapeutic candidate for T2DM management.