Nyctanthes arbor-tristis attenuates hyperglycemia: an integrated experimental and computational investigation

Nyctanthes arbor-tristis Linn. (Oleaceae) is traditionally used for treating metabolic and inflammatory conditions. This investigation aimed to evaluate the antidiabetic potential of the ethanolic leaf extract of N. arbor-tristis through integrated phytochemical, in vitro, in vivo, and in silico approaches. LC-MS analysis revealed 24 bioactive compounds, including flavonoids, phenolic acids, terpenoids, and cucurbitacins. Antioxidant assays demonstrated significant free radical scavenging and reducing activities (DPPH IC₅₀ = 66.56 µg/mL, ABTS = 19.31 µg/mL, FRAP = 3.68 µg/mL), comparable to ascorbic acid. The extract also showed potent inhibition of carbohydrate-hydrolyzing enzymes (α-amylase IC₅₀ = 49.09 µg/mL; α-glucosidase IC₅₀ = 45.52 µg/mL) and enhanced glucose uptake in L6 skeletal muscle cells, reaching 617.45 µg/mL at 500 µg/mL concentration.In vivo, STZ-induced diabetic rats treated with the extract (100-300 mg/kg) for 21 days showed significant reductions in fasting blood glucose, improved oral glucose tolerance, weight restoration, and favorable modulation of lipid profiles. The extract also enhanced antioxidant enzyme activities (CAT, SOD, GPx) and reduced lipid peroxidation (MDA), suggesting oxidative stress attenuation. Molecular docking identified key phytoconstituents with high binding affinity for GLUT1 and α-glucosidase, supporting a multi-targeted mechanism.Collectively, the findings demonstrate the antidiabetic potential of N. arbor-tristis in preclinical experimental models and suggest that enzymatic inhibition, antioxidant effects, and modulation of glucose metabolism may contribute to its biological activity. However, the study is limited to preclinical investigations, and further mechanistic, toxicological, and clinical studies are required to validate these findings.