Identification of Dipeptidyl Peptidase-4 and α-Amylase Inhibitors from Melicope glabra (Blume) T. G. Hartley (Rutaceae) Using Liquid Chromatography Tandem Mass Spectrometry, In Vitro and In Silico Methods

Abstract

The present study investigated the antidiabetic properties of the extracts and fractions from leaves and stem bark of M. glabra based on dipeptidyl peptidase-4 (DPP-4) and α-Amylase inhibitory activity assays. The chloroform extract of the leaves was found to be most active towards inhibition of DPP-4 and α-Amylase with IC50 of 169.40 μg/mL and 303.64 μg/mL, respectively. Bioassay-guided fractionation of the leaves’ chloroform extract revealed fraction 4 (CF4) as the most active fraction (DPP-4 IC50: 128.35 μg/mL; α-Amylase IC50: 170.19 μg/mL). LC-MS/MS investigation of CF4 led to the identification of trans-decursidinol (1), swermirin (2), methyl 3,4,5-trimethoxycinnamate (3), renifolin (4), 4′,5,6,7-tetramethoxy-flavone (5), isorhamnetin (6), quercetagetin-3,4′-dimethyl ether (7), 5,3′,4′-trihydroxy-6,7-dimethoxy-flavone (8), and 2-methoxy-5-acetoxy-fruranogermacr-1(10)-en-6-one (9) as the major components. The computational study suggested that (8) and (7) were the most potent DPP-4 and α-Amylase inhibitors based on their lower binding affinities and extensive interactions with critical amino acid residues of the respective enzymes. The binding affinity of (8) with DPP-4 (−8.1 kcal/mol) was comparable to that of sitagliptin (−8.6 kcal/mol) while the binding affinity of (7) with α-Amylase (−8.6 kcal/mol) was better than acarbose (−6.9 kcal/mol). These findings highlight the phytochemical profile and potential antidiabetic compounds from M. glabra that may work as an alternative treatment for diabetes.

α-Amylase and dipeptidyl peptidase-4 (DPP-4) inhibitory effects of Melicope latifolia bark extracts and identification of bioactive constituents using in vitro and in silico approaches

“…The binding affinity of compound 2 with α-amylase was lower than those previously reported for swermirin and methyl 3,4,5-trimethoxycinnamate in another study (Quek et al. 2020 ).…”

“… 2018 ) and human DPP-4 complexed with drug sitagliptin (PDB ID 1X70) (Quek et al. 2020 ), both of which were retrieved from the Protein Data Bank ( https://www.rcsb.org/pdb ). AutodockTools (ADT) ver.…”

A Comprehensive Review and Perspective on Natural Sources as Dipeptidyl Peptidase-4 Inhibitors for Management of Diabetes

“…The chloroform extract of the leaves of M. glabra effectively inhibited DPP-4 with an IC 50 of 169.40 μg/mL. Computational analysis showed that compounds ( 8 ) and ( 7 ) in this extract are potent DPP-4 inhibitors based on their binding affinities and extensive interactions with important DPP-4 residues [ 93 ]. The phytochemical profiles of these compounds indicated their potential as DPP-4 inhibitors.…”

Determination of Activation Energies and the Optimum Temperatures of Hydrolysis of Starch by α-Amylase from Porcine Pancreas

“…3.2.1.1) catalyze the hydrolysis of α -1,4 glycosidic bonds present in starch, glycogen and other related carbohydrates to low molecular weight products, such as glucose, maltose and maltotriose [ 4 , 5 , 6 , 7 , 8 ]. These enzymes are present in plants, animals and microorganisms [ 9 ] and have extensive applications in medicine [ 10 , 11 , 12 , 13 , 14 ], textiles [ 11 ], detergent [ 11 ], fermentation [ 11 ] and the food industry [ 4 , 11 ].…”

“…In addition to industrial use, α -amylase from porcine pancreas is used for example in health food research [ 16 , 17 , 18 ], to assay resistant starch (RS), not broken down by human enzymes in the small intestine [ 19 ] and is also used in medical diagnostics [ 12 , 13 , 14 ]. One of the problems is effective diagnostic methods allowing for the prognosis of pancreatic cancer of cancer, which is an exceptionally aggressive tumour with high mortality.…”