Essential oils from Plectranthus neochilus plant show potential to inhibit key diabetes enzyme

Computational modelling has suggested that essential-oil compounds from Plectranthus neochilus, particularly citronellyl butyrate and citronellol, may inhibit the enzyme DPP-4 involved in type 2 diabetes, offering a promising foundation for plant-derived antidiabetic drug discovery

A recent study has proposed that essential-oil compounds from Plectranthus neochilus could inhibit dipeptidyl peptidase-4 (DPP-4), an enzyme that regulates glucose metabolism and represents a well-validated target in type 2 diabetes. The work, led by Dr Hamadou Mamoudou and colleagues at the University of Maroua in Cameroon, combined molecular docking with computational pharmacology to identify natural ligands that might match the active pocket of DPP-4 with credible binding energy and acceptable predicted pharmacology.

Plectranthus neochilus itself is a strongly aromatic perennial herb in the mint family, Lamiaceae. It is native to southern Africa, particularly Namibia, Botswana and South Africa and is sometimes known by common names such as ‘lobster flower’, ‘spur flower’ or ‘dogbane’.

Citronellyl butyrate and citronellol emerged as the most promising compounds, with α-terpineol, linalool and isomenthone also showing favourable interactions. Citronellyl butyrate displayed the strongest predicted binding at –7.3 kcal/mol, followed closely by citronellol at –7.2 kcal/mol and citronellyl formate at –7.1 kcal/mol. In these models, more negative values correspond to higher affinity.

While such scores remain below those of marketed inhibitors such as linagliptin or sitagliptin, the researchers argued that the terpenoids’ small size, structural flexibility and ready accessibility make them plausible starting points for optimisation.

“The binding affinity of citronellyl butyrate to DPP-4 was comparable to that of vildagliptin in our reference data,” said Dr. Mamoudou, who led the study.

“This suggests that natural compounds could one day support or complement synthetic antidiabetic drugs by enhancing incretin levels and improving glycaemic control,” he added.

Detailed molecular analysis revealed consistent hydrogen-bonding and hydrophobic interactions across the compounds. Citronellyl butyrate formed hydrogen bonds with Gln510 and Arg560 and fitted into a lipophilic channel framed by Ile529 and Lys512, while citronellol’s hydroxyl group interacted with Asp709 and Lys122 and formed a stabilising π-contact with Phe240.

These contact maps aligned closely with established pharmacophore elements within the DPP-4 binding cavity, which the authors interpreted as evidence of mechanistic plausibility.

Predicted pharmacokinetic properties were broadly favourable. Citronellyl butyrate showed high gastrointestinal absorption, blood–brain barrier permeability, and no violations of standard drug-likeness rules, suggesting potential oral bioavailability. Both citronellol and linalool displayed comparable characteristics with moderate cytochrome P450 inhibition risks but good solubility and diffusion profiles.

Toxicity classifiers signalled modest probabilities for cardiac ion-channel blockade and mutagenicity, but these did not exceed typical early-stage risk thresholds for small, lipophilic molecules.

The research acknowledged the inherent limitations of computational work. Docking algorithms can mis-rank compounds because of uncertainties in side-chain flexibility, protonation and solvation effects. Pharmacokinetic predictions depend on statistical models trained mainly on synthetic molecules, which may not capture the subtleties of monoterpenoid chemistry. Nevertheless, the consistency across multiple scoring functions and interaction patterns was sufficient, the authors wrote, to justify empirical validation.

For further reading please visit: 10.1016/j.cpan.2025.03.002