Identification of phytochemicals in <i>Nyctanthes arbor-tristis</i> leaf: interpreting antidiabetic and antibacterial effect through <i>in vitro</i> and <i>in silico</i> analysis

<i>Nyctanthes arbor-tristis</i> is a traditional medicinal plant in India; however, it is least explored for biological activities. In the present study, antioxidant, mammalian alpha-glucosidase (AG) inhibition, and antibacterial activity of <i>N. arbor-tristis</i> leaf (NL) were determined by <i>in vitro</i> and <i>in silico</i> analysis. Methanolic extract of NL (ME-NL) was prepared. The phytochemical constituents present in ME-NL were tentatively identified using LC-ESI/MS/MS analysis. The inhibition of mammalian AG activities (maltase, sucrase, isomaltase and glucoamylase) and the antibacterial activity of ME-NL were analyzed. Virtual screening of compounds identified in ME-NL for the interaction with human AG (hAG), <i>Escherichia coli</i> dihydropteroate synthase (EDHPS) and <i>Staphylococcus aureus</i> DHPS (SDHPS) was carried out. The best scored four compounds with respective proteins were subjected to molecular dynamics (MD) simulation, post-MD analysis (RMSF, RMSD, 2D-RMSD, PCA, DCCM and FEL) and MM/GBSA analysis. ME-NL was found to be rich in various phenolics and flavonoid compounds. ME-NL showed radical scavenging and ferric reducing antioxidant power activities. ME-NL inhibited all the mammalian AG activities in microgram/ml concentration through a mixed-type of inhibition. ME-NL inhibited both gram-positive and gram-negative bacteria. From the <i>in silico</i> analysis, it was found that among the compounds studied, 3-(4-Hydroxy-3-methoxyphenyl)-1,2-propanediol 2-O-(galloyl-glucoside) (HMPGG) showed stable interactions with hAG and SDHPS; Prupaside (PRU) with hAG; desrhamnosylmartynoside (DRM) with EDHPS; calceolarioside A (CAL) with SDHPS and luteolin 7-rhamnosyl (1->6) galactoside (LRG) with both EDHPS and SDHPS. Altogether, <i>in vitro</i> and <i>in silico</i> analysis revealed the antidiabetic and antibacterial effects of ME-NL, which warrant further <i>in vivo</i> studies.