Phytochemical analysis and bioactive potential of Annona squamosa extracts: Antioxidant and antidiabetic properties assessed through in vitro and In silico approaches

AbstractDiabetes mellitus is a chronic metabolic disorder that necessitates the exploration of safer, plant-based therapeutics. This study investigates the phytochemical composition, antioxidant potential, and antidiabetic properties of Annona squamosa leaf and seed extracts through in vitro assays, GC-MS profiling, molecular docking, and pharmacokinetic analysis. Key bioactive compounds, including flavonoids, alkaloids, triterpenoids, and cardiac glycosides, were identified, with DPPH assays confirming strong antioxidant activity, particularly in ethanol leaf extract (26.53%), highlighting its role in mitigating oxidative stress–a key contributor to diabetes. Molecular docking revealed that Fluorene (-6.9 kcal/mol) and 2-Azetidinone, 3,3-Diphenyl (-7.1 kcal/mol) strongly inhibit alpha-amylase and alpha-glucosidase, outperforming metformin (-4.8 kcal/ mol), thereby indicating significant antidiabetic potential. ADME analysis validated drug-likeness through Lipinski’s Rule Five, while ProTox 3.0 toxicity predictions classified most compounds as moderately safe (Class IV and V). However, fluorene and cyclodecane showed potential neurotoxicity and carcinogenicity, though their low natural abundance reduces concern. This comprehensive study highlights A. squamosa as a promising natural candidate for managing oxidative stress and glucose metabolism, justifying further pharmacological and clinical research to support its development into a phytochemical-based antidiabetic therapeutic.