Antidiabetic functionality of Vitex negundo L. leaves based on UHPLC-QTOF-MS/MS based bioactives profiling and molecular docking insights

•Present study describes the bioactive profiling and α-glucosidase inhibitory activity of Vitex negundo leaves.•Molecular docking studies were performed to explore possible role of identified bioactives towards α-glucosidase inhibition.•60 % ethanolic Vitex negundo extract was ascertained to be potent extract with antidiabetic functionality.•Quantum computational analysis to explore electronic properties of each identified bioactive was also performed. Diabetes is one of the leading causes of death in the world which can be effectively managed by consuming functional foods consisting of medicinal plants. Vitex negundo L. is one of the extensively used plants against wide spectrum of diseases in traditional medicinal systems. Therefore present study was undertaken to explore the bioactive profiling of V. negundo leaves through ultra-high-performance liquid chromatography-quadrupole time of flight/tandem mass spectrometry (UHPLC-QTOF-MS/MS) and α-glucosidase inhibitory potential. Antidiabetic functionality of V. negundo leaves was also explored by molecular docking studies based on binding affinity data and interaction patterns of the potential identified bioactives towards α-glucosidase. Out of different hydro-ethanolic extracts of V. negundo, 60 % ethanolic extract was ascertained to be the potent extract with antidiabetic functionality, showing 2,2-diphenyl-1-picrilhydrazyl (DPPH) radical scavenging activity with half maximal inhibitory concentration (IC50) of 51.18 ± 1.2 μg/mL and α-glucosidase inhibition activity (IC50 of 36.54 ± 0.93 μg/mL). Using UHPLC-QTOF-MS/MS analysis, 15 bioactives were identified from V. negundo leaves extract including; 5,3′-dihydroxy-7,8,4′-trimethoxy flavanone, 6-O-α-D-galactopyranosyl-D-gluconic acid, agnuside, casticin, 7-(α-D-glucopyranosyloxy)-2,3,4,5,6-pentahydroxyheptanoic acid, 2,3-dihydroxybenzoic acid, herbacetin rhamnoside, kaempferol, luteolin-7-glucoside, negundoside, p-hydroxybenzoic acid, protocatechuic acid, quinic acid, vitedoin A, and vitexin. Moreover, intra-molecular charge transfer, energies of frontier molecular orbitals (FMOs), highest occupied molecular orbitals-lowest unoccupied molecular orbitals energy gaps (HOMOs-LUMOs-Egaps), molecular electrostatic potential (MEP), and ionization potential (IP) of each identified bioactive were also explored. The findings unveil the 60 % hydro-ethanolic leaf extract of V. negundo as a natural source of potent antidiabetic bioactives, hence could be used to develop