Molecular Docking Study of Standardized Lime (Citrus aurantiifolia) Peel Decoction as an Antidiabetic Herbal

Diabetes mellitus (DM) is a chronic endocrine, metabolic disease characterized by elevated blood glucose levels that will affect more than 500 million adults in 2021. Citrus aurantiifolia peels are discarded by-products that contain flavonoid compounds, offering potential as an antidiabetic herb. This study aims to evaluate C. aurantiifolia water extract (CPWE) compounds responsible for antidiabetic properties through α-glucosidase, α-amylase, and sodium-glucose transporter 2 (SGLT-2) inhibitor using molecular docking simulation. CPWE was extracted using ultrasonic-assisted extraction (UAE) with distilled water, and its chemical profile was then analyzed using LC-MS/MS. Compounds detected in LC-MS/MS were tested for antidiabetic activity using molecular docking simulation carried out using Molegro Virtual Docker into α-glucosidase (PDB ID: 3A4A), α-amylase (PDB ID: 1OSE), SGLT-2 (PDB ID: 7VSI), and dipeptidyl peptidase 4 (DPP-4) (PBD ID: 3G0B). The major compounds found in CPWE were hesperidin, limonin, and scoparone, along with other compounds, including hesperetin, naringin, naringenin, bergaptol, citric acid, quercetin, and rutin. Molecular docking simulation demonstrates that rutin inhibited α-glucosidase, α-amylase, and DPP-4, hesperidin inhibited α-amylase, SGLT-2, and DPP-4, and naringin inhibited SGLT-2. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction of CPWE compounds showed that active compounds have limited absorption and permeability, but none of the CPWE compounds are toxic. Molecular docking predictions of 10 compounds from CPWE revealed that flavonoid compounds have antidiabetic potential.