GC-MS, alpha-amylase, and alpha-glucosidase inhibition and molecular docking analysis of selected phytoconstituents of small wild date palm fruit (Phoenix pusilla).

Phoenix pusilla (Arecaceae), commonly known as "small wild date palm", is regarded as one of the underutilized fruit crops in South India. Methanol extract of P. pusilla ripened fruits (PPRF) was analyzed for in vitro porcine pancreatic alpha-amylase (PPAA) and rat small intestine alpha-glucosidase (RIAG) inhibition activities, and through gas chromatography-mass spectrometry (GC-MS) analysis. The GC-MS analysis showed the presence of 25 phytoconstituents from PPRF which was further assessed on the docking behavior of five targeted enzymes diabetes mellitus (DM) namely (i) human aldose reductase, (ii) protein tyrosine phosphatase 1B, (iii) pancreatic alpha-amylase, (iv) peroxisome proliferator-activated receptor gamma, and (v) dipeptidyl peptidase IV by using the AutoDock Vina method. In addition to this physicochemical, bioactivity score, absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis was performed using the Molinspiration and pkCSM free online servers. Methanolic extract of PPRF showed 50% inhibition concentration (IC50) at 69.86 and 72.60 µg/mL levels against PPAA and RIAG enzymes activities, respectively. Interestingly in the present study, GC-MS analysis showed the presence of 25 phytoconstituents from PPRF. Physicochemical analysis of PPRF has exhibited that 13 ligands have complied well with Lipinski's Rule of Five (RoF). With regard to ADMET analysis, one ligand (9,12-octadecadienoic acid [Z,Z]) has predicated to possess both the hepatotoxicity (HT) and skin sensitization (SS) effect. The docking studies showed that 1-formyl-2,5-dimethoxy-6,9,10-trimethyl-anthracene exhibited the maximum atomic contact energy (ACE) for all the five target enzymes of DM. Thus, the current study suggested that the methanolic extract of PPRF and its phytoconstituents could be considered as potent antidiabetic agents.