Microwave-assisted optimization extraction for green chili paste and investigation of its alpha-glucosidase inhibitory activity with molecular docking and molecular dynamics simulation for anti-diabetic potential

Abstract

Type 2 diabetes (T2D) is a growing global health concern, necessitating alternative therapeutic strategies to regulate postprandial glucose levels. α-Glucosidase inhibitors (AGIs) delay glucose absorption but are often associated with adverse effects. Plant-based AGIs offer promising alternatives with potential efficacy and improved safety. Green chili paste (GCP), a staple in Thai cuisine, contains bioactive phytochemicals that may exhibit α-glucosidase inhibitory activity. This study optimized the microwave-assisted extraction of GCP using the Box-Behnken design (BBD) and response surface methodology (RSM). Microwave-assisted extraction was employed as a green and sustainable approach, reducing solvent usage and energy consumption while enhancing bioactive compound yield. Metabolomic analysis revealed key phytochemicals in the optimized GCP extract, including hesperidin, apigenin, luteolin, and capsaicin, which were further quantified using LC-ESI-MS/MS. In vitro assays demonstrated that the optimized GCP extract exhibited α-glucosidase inhibition comparable to synthetic inhibitors, with synergistic effects observed in combination with acarbose and miglitol. Molecular docking and molecular dynamics simulation confirmed the strong binding affinities of GCP-derived compounds to α-glucosidase, supporting their inhibitory potential. The Ames test confirmed the extract is non-genotoxic, ensuring its preliminary safety. In summary, this study highlights optimized GCP extract as a promising, natural alternative for T2D management while promoting sustainability through the use of eco-friendly extraction techniques. The findings warrant further clinical validation for future applications as a functional ingredient, contributing to sustainable and health-conscious dietary interventions.