Triterpene saponins from Barringtonia acutangula (L.) Gaertn as a potent inhibitor of 11β-HSD1 for type 2 diabetes mellitus, obesity, and metabolic syndrome

Abstract

Abstract Background Barringtonia acutangula (L.) Gaertn, Garcinia indica (Thouars) Choisy, and Feronia limonia (L.) Swingle is widely utilized in traditional folk medicine against diabetes, obesity, and metabolic syndrome but lacks the evidence of compound-protein interaction for the treatment. Methods Phytocompounds were retrieved from herbs databases and public repositories. Probable protein targets were predicted using BindingDB (p ≥ 0.7). The pathways modulated by compounds were analyzed using the STRING and KEGG pathways. The compound-protein-pathway network was constructed using Cytoscape v3.6.1. Druglikeness was predicted by Molsoft. Docking was performed by AutoDock vina by PyRx 0.8v. Results Among three plants, eleven triterpene saponins from B. acutangula showed druggable characteristics and identified to inhibit the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1/HSD11B1) as a key protein target and also inhibit/modulate other 27 protein molecules involved in the 3 major pathways i.e. Metabolic syndrome, cGMP-PKG signaling, and insulin resistance pathways and also these compounds showed interactions with the active site amino acid residues of 11β-HSD1. Among eleven compounds Barringtogenol B scored the highest binding affinity by forming a hydrogen bond with Ile218 active site residue of 11β-HSD1. Conclusion Triterpene saponins contained in B. acutangula bark and seed inhibits 11Β-HSD1 and this multi-compound contained enriched fraction could be the potent treatment regimen for T2DM, obesity, and MetS.