LAUSR

Abstract Sesbania grandiflora L. Poir is an edible medicinal plant widely distributed in Asian countries. One of its folk medicinal uses is the alleviation or treatment of Type 2 Diabetes mellitus (T2DM). A number of animal studies confirmed its use in treating T2DM; however, none of them explored the chemistry or the possible mechanism. This study aims to unveil the chemical profile of S. grandiflora through LC-HRMS dereplication analysis, followed by isolation, identification and quantification of the major secondary metabolites with potential α-amylase and α glucosidase inhibitory effect as the potential anti-diabetic mechanism. LC-HRMS chemical profiling of its leaves and twigs identified 32 metabolites. Bio-guided fractionation and HPLC purification led to the isolation of 14 major metabolites that were screened for their α-amylase and α-glucosidase inhibitory activities. For the first time, two terpenoids; vomifoliol (11) and loliolide (14) showed inhibitory effect against α-glucosidase with IC50 values of 64.5 and 388.48 µM, respectively. Quercetin (10) exhibited the highest α-glucosidase inhibition with IC50 value of 17.45 µM. Further, predicated molecular modelling studies demonstrated strong binding interactions between active compounds and enzyme-substrate binding pockets supporting the observed enzyme inhibitory activity. Interestingly, the quantitative analysis of the most potent inhibitors indicated their existence at a high percentage within S. grandiflora extract. Our findings suggested S. grandiflora is a useful dietary supplement to control postprandial blood glucose.