Safety Study and Molecular Docking Analysis of Phyto-Constituents from Leaves: Insights into Dipeptidyl Peptidase-4 (DPP-4) Inhibition and Therapeutic Potential.

Background: Medicinal plants form the foundation of healthcare systems and modern medicine, offering powerful therapeutic potential to combat a wide range of chronic metabolic disorders.

Objective: Th present study evaluates the safety of leaf extracts using rodent modeling for 56 days. It also explores the molecular docking interactions of leaf phytoconstituents with the dipeptidyl peptidase-4 (DPP-4) receptor.

Methodology: A total of 20 rats were divided into 5 groups (G0: Normal diet, G1: 0.25% WS leaves Extract, G3: 0.5% WS leaves Extract, G4: 0.5% WS leaves powder, and G5: 1% WS leaves powder) for 56 days. The organ-to-body weight ratio, LFTs, RFTs, and hematological profile were determined in the 4th and 8th weeks. On the other hand, the structures of compounds identified from the methanolic extract of leaves were modified into PDBQT format to perform molecular docking.

Results: The results showed that all parameters varied within normal ranges. The hematological parameters were higher in G2 after the 28th day compared to the values after the 56th day. The maximum values of serum glucose and lipid parameters were found in the G3 group as compared to other groups, while hepato-renal markers were high in G0. Molecular docking revealed the binding affinity of w-02, w-03, w-04, w-05, and w-07 with DPP-4 receptors; moreover, w-04 had the highest binding affinity of -6.4 kcal/mol.

Conclusion: The 0.5% leaves extract of revealed positive effect on hematological and biochemical profile of rats without causing any adverse effects.