Moroccan virgin olive oil triterpenes: HPLC-DAD-ELSD profiling and computational investigation of anti-diabetic potential

Introduction: Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia due to impaired insulin secretion or resistance. Conventional treatments like acarbose, miglitol, and voglibose inhibit carbohydrate-digesting enzymes but often cause adverse effects and have bioavailability limitations. This has led to interest in plant-derived bioactive compounds as safer alternatives. Oleanolic and maslinic acids in Moroccan virgin olive oil have shown potent inhibitory activity against α-glucosidase and α-amylase, enzymes regulating postprandial glucose levels. Methods: This study quantified the levels of oleanolic and maslinic acids in olive oils from various Moroccan regions, considering factors such as olive variety, maturity index, production method, and geographic origin. Pharmacokinetic properties were assessed using in silico ADME analysis. Molecular docking was performed to evaluate inhibitory interactions with α-amylase and α-glucosidase. Molecular dynamics (MD) simulations (1000 ns) assessed complex stability, and MM-PBSA calculations determined binding free energies. Results: The concentrations of oleanolic and maslinic acids varied across olive oil samples. The Moroccan Picholine variety had the highest levels (58.3 mg/kg for maslinic acid and 55.06 mg/kg for oleanolic acid). Olive oil from the two-phase milling method contained higher concentrations than the three-phase system, and lower maturity index olives showed greater concentrations. Pharmacokinetic analysis indicated favorable drug-likeness properties for these bioactive compounds. In silico docking suggested notable binding of maslinic acid to α-amylase (-41.42 kJ/mol) and oleanolic acid to α-glucosidase (-32.22 kJ/mol), with interactions involving key amino acid residues. Molecular dynamics simulations indicated stable ligand-enzyme interactions, and MM-PBSA analysis estimated binding energies of -39.05 ± 16.78 kJ/mol for the maslinic acid-α-amylase complex and -13.97 ± 7.08 kJ/mol for the oleanolic acid-α-glucosidase complex. Conclusion: Moroccan virgin olive oil, rich in oleanolic and maslinic acids, may serve as a natural alternative for diabetes management by modulating key enzymatic pathways involved in glucose metabolism.