Ultrasound-assisted extraction of mangiferin from Mangifera pajang Kosterm. fruit using choline chloride-based natural deep eutectic solvent: Optimisation and antidiabetic activity

Abstract

The growing demand for sustainable bioresources has highlighted the importance of exploring underutilised plant species as alternative sources of health-promoting compounds. Mangifera pajang Kosterm. (bambangan), an endemic and underexploited fruit native to Borneo, particularly Sabah, Malaysia, offers considerable potential as a sustainable source of bioactive constituents. However, research on efficient extraction techniques and processing technologies to recover its valuable phytochemicals remains limited. In this study, one-factor-at-a-time (OFAT) was used for parameter screening, followed by response surface methodology with central composite design to optimise ultrasound-assisted extraction using natural deep eutectic solvent (NADES). Parameters including extraction time, solid-to-solvent ratio, and ultrasonic amplitude were evaluated to maximise crude yield and mangiferin content. Bioactivity was assessed through antioxidant and antidiabetic assays based on half-maximal inhibitory concentration (IC₅₀) values of the optimised M. pajang fruit extract (OMPFE) compared with positive controls. Molecular docking was performed against α-glucosidase. ADMET and drug-likeness were predicted to evaluate pharmacokinetic behaviour and oral drug-likeness properties. The optimised conditions were 11 min extraction time, solid-to-solvent ratio of 1:33 g/mL, and ultrasonic amplitude of 53%, yielding 70.32% ± 1.20% crude extract and 0.64 ± 0.02 mg/g mangiferin. In vitro, OMPFE exhibited antioxidant (IC₅₀ = 121.15 ± 1.65 μg/mL) and antidiabetic (IC₅₀ = 93.67 ± 1.68 μg/mL) activities. In silico, mangiferin (−8.0 kcal/mol) showed stronger binding affinity to α-glucosidase compared with acarbose (−6.4 kcal/mol). ADMET and drug-likeness prediction further revealed higher intestinal absorption, better renal clearance, fewer rule violations, and stronger membrane permeability for mangiferin compared with acarbose, although solubility was lower. These findings suggest that M. pajang fruit represents a promising sustainable source of nutraceuticals and functional food products for managing oxidative stress and diabetes.