Sesbania grandiflora L. Poir leaves: a dietary supplement to alleviate type 2 diabetes through metabolic enzymes inhibition

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.