Evaluation of In-silico and In-vitro Anti- Diabetic Efficacy of Phytochemicals of Phoenix dactylifera

Abstract

Abstract : Type 2 diabetes mellitus (T2DM) is a widespread chronic disease that threatens individual health and increases mortality due to complications. Phoenix dactylifera, an indigenous Bahraini plant known as the palm tree, contains phytochemicals with potent medicinal effects against various diseases, including diabetes. Plant-derived antihyperglycemic agents represent a promising avenue for novel drug discovery, offering a cost-effective, accessible, and potentially safer alternative to synthetic drugs. This research aims to analyze the phytochemical compounds of P. dactylifera and assess the inhibitory kinetic mechanism of the lead compound against diabetic-related enzymes. In silico network pharmacology and molecular simulation are carried out using multiple bioinformatics software, considering the ADMET profile for potential therapeutic effects. A total of 17 bioactive compounds retrieved from IMPPAT were found with high drug likeness and oral bioavailability extracted from P. dactylifera. Exploring compound characteristics using the ADMET profile eliminates poor pharmacokinetic properties at early development stages. 5-O-caffeoylshikimic acid is a phenolic compound that interacts with proteins enrolled in diabetic-related pathways, according to the Metascape and ShinyGo databases. Molecular docking in PyRx revealed strong binding affinities of 5-O-caffeoylshikimic acid to α-amylase (-7.7 kcal/mol) and α-glucosidase (-7.8 kcal/mol), indicating a stable and potent interaction In vitro enzyme inhibition kinetics are implemented to confirm the effectiveness of the in silico findings of the compound against α-amylase and α-glucosidase and to determine the required IC50 value. 5-O-caffeoylshikimic acid was found to have a strong inhibition with an IC50 of 17.862 µM against α-amylase and 7.668 µM against α-glucosidase, in contrast to acarbose, the positive control, with IC50s of 8.621 µM and 30.978 µM, respectively. 5-O-caffeoylshikimic acid has a significant inhibitory effect against the main digestive enzymes that trigger T2DM progression as an anti-hyperglycemic compound, suggesting a promising compound for use in diabetic patients