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

• Main Authors: Alexandra Quek, Nur Kartinee Kassim, Amin Ismail, Muhammad Alif Mohammad Latif, Khozirah Shaari, Dai Chuan Tan, Pei Cee Lim
• Format: Article
• Language: English
• Published: MDPI AG 2021-12-01
• Series: Molecules
• Subjects: <i>Melicope glabra</i>; antidiabetic; diabetes; DPP-4; α-Amylase; molecular docking
• Online Access: https://www.mdpi.com/1420-3049/26/1/1

The present study investigated the antidiabetic properties of the extracts and fractions from leaves and stem bark of <i>M. glabra</i> 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 (<b>1</b>), swermirin (<b>2</b>), methyl 3,4,5-trimethoxycinnamate (<b>3</b>), renifolin (<b>4</b>), 4′,5,6,7-tetramethoxy-flavone (<b>5</b>), isorhamnetin (<b>6</b>), quercetagetin-3,4′-dimethyl ether (<b>7</b>), 5,3′,4′-trihydroxy-6,7-dimethoxy-flavone (<b>8</b>), and 2-methoxy-5-acetoxy-fruranogermacr-1(10)-en-6-one (<b>9</b>) as the major components. The computational study suggested that (<b>8</b>) and (<b>7</b>) 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 (<b>8</b>) with DPP-4 (−8.1 kcal/mol) was comparable to that of sitagliptin (−8.6 kcal/mol) while the binding affinity of (<b>7</b>) 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 <i>M. glabra</i> that may work as an alternative treatment for diabetes.