Saponins from <i>Spondias mombin</i> leaves as potential PPAR gamma agonist and DPP-4 inhibitor for type 2 diabetes treatment using molecular docking studies and ADMET profiling

Abstract

Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors and peroxisome proliferator-activated receptor gamma (PPARγ) agonists are available for the clinical treatment of diabetic mellitus (DM), although the majorities have numerous negative side effects. Emerging research suggests that natural compounds, particularly those derived from medicinal plants, hold significant potential, driven by their perceived safety and bioavailability. This study seeks to determine the potential of saponins isolated from Spondias mombin as novel DPP-4 inhibitors and PPARγ agonist by examining their interaction with the enzyme based on the results of molecular docking studies, strength of their interaction, drug likeness and pharmacokinetic analysis. 

Materials and methods: Saponins were isolated from the leaves of Spondias mombin and characterized using high performance liquid chromatographic procedure. Molecular docking studies was used to determine the interactions between the saponins and key anti diabetic drug targets PPAR-γ and DPP-IV The 2D diagrams and the 3D (surface) views of the protein-ligand interactions were done using Discovery studio software and Pymol software respectively, while the pharmacokinetics and drug likeness properties of the studied compounds were estimated using SwissAdme online server.

Results: Eleven saponins: Hispigenin, Solagenin, Diosgenin, Trigogenin, Neochlorogenin, Hecogenin, Sapogenin, Tribuloin, Yangonenin, Conyzorgin, Saponine were characterized from the leaves of Spondias mombin. Solagenin stood out as the most potent activator of PPARγ while Hecogenin was the most potent inhibitor of DPP-4. The results indicated that only Hispigenin, hecogenin, yangonenin and solagenin adhered to all four Lipinski's rules. The saponins showed no Veber violations, and readily crossed the blood brain barrier. A high gastrointestinal absorption was also shown for most of the saponins.  None of the seven saponins (Hispigenin, Hecogenin, Solagenin, Diosgenin, Trigogenin, neochlorogenin, and Sapogenin) appear to be inhibitors of four key cytochrome p450 isoenzymes.

Conclusion: The study has shown that the saponins of Spondias mombin are drug like, highly absorbed and bioavailable and hence adding to the increasing amount of data demonstrating the effectiveness of natural products in treating type 2 diabetes.