Antioxidant and Antidiabetic Activity of the Bulb Extract of Crinum amoenum Roxb. ex Ker Gawl: An Integrated In Vitro, In Vivo and In Silico Approach

Crinum amoenum Roxb. ex Ker Gawl. (C. amoenum) is traditionally used in Nepal, but its antidiabetic potential remains insufficiently validated. This study characterized the 80% (v/v) ethanol bulb extract of C. amoenum and evaluated its antioxidant, α-amylase inhibitory, hypoglycemic, molecular docking, molecular dynamics (MD) simulation, and ADMET profiles. The ethanolic bulb extract was evaluated through phytochemical screening, thin-layer chromatography, total phenolic content (TPC), total flavonoid content (TFC) estimation, LC-MS analysis, antioxidant assays, α-amylase inhibition assays, acute toxicity testing, and hypoglycemic/oral glucose tolerance test (OGTT) studies in Wistar rats. Lycorine, pratorinine, and palmatine were docked against α-amylase (PDB ID: 5U3A) and GLP-1R (PDB ID: 6GB1), followed by 200 ns MD simulations and ADMET prediction. Qualitative analysis of the extract was positive for flavonoids, phenolic compounds, tannins, saponins, alkaloids, and carbohydrates, and a positive Salkowski reaction indicated the presence of constituents occurring in glycosidic form. The TPC was 173.38 ± 1.22 mg GAE/g, and the TFC was 314.58 ± 0.09 mg QE/g. LC-MS tentatively annotated lycorine, pratorinine, and palmatine based on retention time, m/z values in positive-mode electrospray ionization, and comparison with previously reported spectral information. The extract showed DPPH scavenging activity (IC50: 90.98 μg/mL) and strong α-amylase inhibition (IC50: 49.31 μg/mL) compared with acarbose (IC50: 51.51 μg/mL). No deaths were observed following oral administration at 5000 mg/kg to rats. The 500 mg/kg dose produced the greatest hypoglycemic response, reducing blood glucose by 35.78% at 120 min in non-diabetic Wistar rats and by 19.21% at 60 min in glucose-loaded rats. Among all the compounds tested, pratorinine demonstrated the highest docking affinity with α-amylase (−8.2 kcal/mol; ASP300) and GLP-1R (−7.0 kcal/mol; GLY132). MD simulation supported greater stability of the α-amylase complex, and ADMET prediction identified pratorinine as a comparatively favorable predicted lead candidate (LD50: 1000 mg/kg; Class 4 toxicity category). Pratorinine was identified as the most promising in silico antidiabetic candidate from the C. amoenum extract, primarily due to stable α-amylase interactions and favorable ADMET properties.