Integrated In Vitro and In Silico Evaluation of Lotus (Nelumbo nucifera) Seed Extracts for Antioxidant, Antimicrobial, and Antidiabetic Potentials.

The increasing incidence of diabetes and antimicrobial resistance highlights the urgent need for plant-based therapeutics with multifunctional health benefits. This study evaluated the phytochemical composition and biological activities of lotus (Nelumbo nucifera) seed extracts obtained via Soxhlet extraction (SL) and ultrasonic-assisted extraction (UL) using methanol as the extraction solvent. The UL extract showed higher yield and greater total phenolic (107.92 mg GAE/g) and flavonoid (104.89 mg QE/g) contents compared with SL. UHPLC-DAD analysis identified p-coumaric acid (5.60 mg/g) and chlorogenic acid (4.27 mg/g) as the dominant constituents in UL. The UL extract exhibited superior antioxidant activity DPPH• (IC50: 17.51 µg/mL), although lower than the reference standards ascorbic acid (IC50: 12.74 µg/mL) and BHT (IC50: 10.74 µg/mL). It also demonstrated notable enzyme inhibition against α-amylase (IC50: 12.54 µg/mL), comparable but slightly weaker than the standard acarbose (IC50: 10.73 µg/mL), and α-glucosidase (IC50: 49.21 µg/mL), relative to acarbose (IC50: 43.14 µg/mL). In contrast, the SL extract exhibited stronger antimicrobial activity, particularly against Staphylococcus aureus (MIC: 1.0 mg/mL). Molecular docking analysis identified rutin (-9.4 kcal/mol) as the most potent α-amylase inhibitor, supported by favorable ADMET properties and predicted high gastrointestinal absorption. These findings suggest that lotus seed extracts, particularly those obtained via ultrasonic extraction, represent promising candidates for functional food development and phytopharmaceutical applications in oxidative stress and diabetes management.