Ultrasound-assisted extraction of mangiferin from Mangifera pajang Kosterm. fruit using a 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, M. pajang fruit was pretreated using ultrasound-assisted osmotic dehydration (UAOD), and the one-factor-at-a-time (OFAT) method was subsequently used for parameter screening, followed by a response surface methodology with central composite design to optimise ultrasound-assisted extraction using a natural deep eutectic solvent (NADES). Parameters including extraction time, solid-to-solvent ratio, and ultrasonic amplitude were evaluated to maximise total phenolic content (TPC), total flavonoid content (TFC), and mangiferin content. Bioactivity was assessed through antioxidant and antidiabetic assays based on IC₅₀ values of the optimised M. pajang fruit extract (MPFE) compared with positive controls. Molecular docking was performed against α-glucosidase. ADMET and drug-likeness were predicted to evaluate the potential pharmacokinetic behaviour and oral drug-likeness properties of mangiferin. The optimised conditions were an extraction time of 11.33 min, a solid-to-solvent ratio of 1 : 28.52 g mL⁻¹, and an ultrasonic amplitude of 51.41%, achieving 53.02 ± 1.57 mg GAE g⁻¹ TPC, 17.26 ± 1.13 mg RE g⁻¹ TFC, and 0.66 ± 0.01 mg g⁻¹ mangiferin. In vitro, the MPFE exhibited antioxidant (IC₅₀ = 117.58 ± 2.19 µg mL⁻¹) and antidiabetic (IC₅₀ = 90.54 ± 1.60 µg mL⁻¹) activities. In silico, mangiferin (−8.0 kcal mol⁻¹) showed stronger binding affinity to α-glucosidase compared with acarbose (−7.3 kcal mol⁻¹). ADMET and drug-likeness prediction further revealed that mangiferin showed higher intestinal absorption, better renal clearance, fewer rule violations, and stronger membrane permeability than 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, although further experimental validation remains necessary.