LC–MS Based Phytochemical Profiling and In Silico Multi-Target Evaluation of Passiflora tarminiana against α-Amylase and α-Glucosidase

Several Passiflora species have been documented to exhibit anti-diabetic properties. Hence, the study presents the first insight into the phytochemical profile of an aqueous extract of Passiflora tarminiana indigenous to the Nilgiris, through LC-MS-based analysis with molecular docking to identify and prioritize potential multitarget bioactive compounds for antidiabetic activity. Diabetes mellitus, characterised by impaired blood glucose levels, poses a formidable public health challenge. Although many inhibitors targeting starch-hydrolysing enzymes are available, natural inhibitors are considered safe. Therefore, an in silico approach was used to analyze potential phytochemicals as major antidiabetic targets. These phytochemicals were characterized by LC-MS/MS, followed by preliminary phytochemical screening. The qualitative phytochemical results analyzed the presence of alkaloids, flavonoids, glycosides, saponins, and terpenoids. The total phenolic content (TPC) (373.81 ± 18 µg/mL GAE) and total flavonoid content (TFC) (271.96 ± 20 µg/mL QE) were determined in the aqueous extracts of the fruit. LC-MS/MS profiling revealed 54 compounds, 24 of which exhibited potential anti-diabetic activity. ADMET properties confirmed that 20 compounds satisfied Lipinski’s rule and revealed drug-likeness and good bioavailability. Molecular docking against α-amylase and α-glucosidase prioritized Maritimetin, Diprogulic acid, and Pirbuterol as promising compounds based on their favorable binding affinities. Furthermore, the stability was examined using molecular dynamics (MD) simulations through trajectorybased analyses (RMSD, RMSF, and hydrogen bonding) and conformational stability assessments, including radius of gyration (Rg), solvent-accessible surface area (SASA), and PCA-derived free energy landscapes. The MMPBSA calculations demonstrated favourable binding free energies of the selected compounds compared to acarbose, supporting the robustness of the findings. However, the analysis is limited by the lack of experimental validation through enzyme inhibition and kinetic studies, and the LC-MS-based compound identifications remain tentative, as they were not confirmed using reference standards.”