Computational investigation of Plectranthus neochilus essential oil phytochemicals interaction with dipeptidyl peptidase 4: A potential avenue for antidiabetic drug discovery

Abstract

This study explores the antidiabetic potential of essential oil compounds from Plectranthus neochilus through molecular docking and pharmacological analysis targeting dipeptidyl peptidase-4 (DPP-4), a key enzyme in type 2 diabetes management. Citronellyl butyrate exhibited the highest binding affinity (−7.3 kcal/mol), followed by citronellol (−7.2 kcal/mol), citronellyl formate (−7.1 kcal/mol), and linalool (−6.7 kcal/mol), indicating strong inhibitory potential against DPP-4. Molecular interactions revealed that citronellol forms hydrogen bonds with Asp709 and Lys122, alongside π-π interactions with Phe240, enhancing binding stability. Citronellyl butyrate demonstrated favorable pharmacokinetic properties, including high gastrointestinal absorption (logP: 4.03), blood-brain barrier permeability, and moderate CYP2C9 inhibition, aligning with Lipinski’s Rule of Five. Citronellol showed high gastrointestinal absorption (68 %) and moderate blood-brain barrier penetration (36.13 %), with a moderate bioavailability, warrants further investigation. Toxicity profiles indicated low acute oral toxicity (LD50: 1.81 and 2.03 -log(mol/kg) for citronellyl butyrate and citronellol, respectively) and moderate risks for drug-induced liver injury (44.81 % and 45.4 %) and mutagenicity (36.35 % and 39.39 %). α-terpineol and isomenthone exhibited good absorption (log P: 2.49 and 2.60) and low metabolic interaction risks, supporting their therapeutic potential. These findings highlight the potential of P. neochilus essential oil compounds as natural DPP-4 inhibitors, offering a novel approach to diabetes management.