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

• Published in: Molecules (Basel, Switzerland) Switzerland), 2020-12, Vol.26 (1), p.1
• Main Authors: Quek, Alexandra, Kassim, Nur Kartinee, Ismail, Amin, Latif, Muhammad Alif Mohammad, Shaari, Khozirah, Tan, Dai Chuan, Lim, Pei Cee
• Format: Article
• Language: English
• Subjects: Acarbose; Affinity; alpha-Amylases - chemistry; Amylases; antidiabetic; Antidiabetics; Bark; Binding; Carbohydrates; Chloroform; Chromatography, Liquid; Computer applications; Diabetes; Diabetes mellitus; Dimethyl ether; Dipeptidyl Peptidase 4 - chemistry; Dipeptidyl-peptidase IV; Dipeptidyl-Peptidase IV Inhibitors - chemistry; Dipeptidyl-Peptidase IV Inhibitors - pharmacology; DPP-4; Enzymes; Flavonoids; Fractionation; Glucagon; Glucose; Glycoside Hydrolase Inhibitors - chemistry; Glycoside Hydrolase Inhibitors - pharmacology; Hyperglycemia; In vitro methods and tests; Inhibitors; Insulin; Leaves; Liquid chromatography; Mass spectrometry; Mass spectroscopy; Melicope glabra; Metabolism; Metabolites; molecular docking; Molecular Docking Simulation; Molecular Dynamics Simulation; Peptidase; Peptidases; Phytochemicals; Phytochemicals - chemistry; Plant Extracts - chemistry; Plant Extracts - pharmacology; Rutaceae - chemistry; Tandem Mass Spectrometry; α-Amylase
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26010001

The present study investigated the antidiabetic properties of the extracts and fractions from leaves and stem bark of 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 IC 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 IC : 128.35 μg/mL; α-Amylase IC : 170.19 μg/mL). LC-MS/MS investigation of CF4 led to the identification of trans-decursidinol ( ), swermirin ( ), methyl 3,4,5-trimethoxycinnamate ( ), renifolin ( ), 4',5,6,7-tetramethoxy-flavone ( ), isorhamnetin ( ), quercetagetin-3,4'-dimethyl ether ( ), 5,3',4'-trihydroxy-6,7-dimethoxy-flavone ( ), and 2-methoxy-5-acetoxy-fruranogermacr-1(10)-en-6-one ( ) as the major components. The computational study suggested that ( ) and ( ) 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 ( ) with DPP-4 (-8.1 kcal/mol) was comparable to that of sitagliptin (-8.6 kcal/mol) while the binding affinity of ( ) 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 that may work as an alternative treatment for diabetes.