Molecular docking and in vitro studies of soap nut trypsin inhibitor (SNTI) against phospholipase A2 isoforms in therapeutic intervention of inflammatory diseases

Abstract

Therapeutic value of allelochemicals in inflammatory disorders and the potential drug targets need to be elucidated to alleviate tissue and vascular injury. Natural anti-inflammatory agents are known to cause minimal adverse effects. Presence of different secondary metabolites (allelochemicals), protease inhibitors like soap nut trypsin inhibitor (SNTI) from Sapindus trifoliatus and allied compounds from natural sources cannot be blithely ignored as natural therapeutics. In the present study, SNTI, a prospective protease inhibitor isolated from the seeds of Sapindus trifoliatus were subjected to docking against three isoforms of Phospholipase A₂ (PLA₂) molecules of the inflammatory pathways which are localized in the membrane, cytosol and pancreas. Eleven ligand molecules were selected from Sapindus trifoliatus and docked against membrane, cytosolic and pancreatic PLA₂. Cytosolic PLA₂ showed a strong inhibition by Kampferol, a secondary metabolite from seed endosperm of Sapindus trifoliatus. SNTI showed best interaction with membrane PLA₂ in both in silico as well as in in vitro studies. SNTI showed IC₅₀ value of 29.02 μM in in vitro assay. Docking interaction profiles and in vitro studies validate selected molecules from Sapindus trifoliatus as immunomodulators and can mollify inflammatory responses.

Keywords: Allelochemicals; Docking; Homology modeling; PLA(2); Protein interaction; SNTI; sPLA(2).