Antidiabetic potential of Sapindus trifoliatus fruit ethanolic extract: Gas chromatography-mass spectrometry profiling, molecular docking, and in vitro/in vivo evaluation

Diabetes mellitus causes vascular, renal, and ocular complications. In this study, we evaluated an ethanolic extract of Sapindus trifoliatus fruit using gas chromatography-mass spectrometry (GC-MS) profiling, molecular docking, and in vitro and in vivo assays. GC-MS analysis revealed key bioactive phytochemicals, and docking analysis demonstrated strong AKR1C3 binding. Acute toxicity testing confirmed safety at doses up to 5000 mg/kg. In alloxan-induced diabetic mice, extract treatment dose dependently lowered fasting blood glucose and HbA1c levels, restored pancreatic, hepatic, and cardiac histology, and mitigated ocular, renal, and cardiac damage. In in vitro, the extract inhibited α-amylase and α-glucosidase, supporting its antihyperglycemic activity. Compared to previous studies, S. trifoliatus extract showed enhanced efficacy, likely due to its antioxidant and anti-inflammatory properties, underscoring its potential as a plant-based antidiabetic therapy.