Introduction: To identify and evaluate phytochemicals from Syzygium cumini (Indian blackberry) as potential natural Dipeptidyl Peptidase-4 (DPP-4) inhibitors for the management of Type 2 Diabetes Mellitus (T2DM), aiming to find safer alternatives to synthetic inhibitors that are often associated with severe side effects. Methods: We employed different in-silico approaches to screen the phytochemicals of S. cumini for their DPP-4 inhibitory potential. Firstly, Molecular docking was performed to evaluate binding affinities with DPP-4. Subsequently, a PASS (Prediction of Activity Spectra for Substances) analysis was performed to confirm the antidiabetic potential. Furthermore, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) profiling was conducted to assess pharmacokinetic properties. Lastly, Molecular dynamics (MD) simulations lasting 50 nanoseconds were performed to analyze the structural stability of protein-ligand complexes. Results: Three phytochemicals, namely astragalin, bergenin, and maslinic acid, demonstrated strong binding affinities, with docking scores of -8.4, -7.2, and -8.8, respectively. Bergenin exhibited the highest structural compactness in MD simulations, as indicated by the radius of gyration. ADMET analysis suggested all three compounds exhibited favourable pharmacokinetic and safety profiles. Discussion: The present study provides valuable insights into the potential of S. cumini phytochemicals as natural DPP-4 inhibitors. While further in-vitro and in-vivo validation is recommended, the findings offer a promising foundation for the development of safe, plant-derived therapeutics that could complement existing antidiabetic strategies. Conclusion: Phytochemicals from S. cumini, particularly astragalin, bergenin, and maslinic acid, show promise as natural DPP-4 inhibitors with potential application in T2DM treatment. These compounds offer a safer alternative to synthetic drugs.
Abbas et al. (Mon,) studied this question.