Flavanol concentrations do not predict dipeptidyl peptidase-IV inhibitory activities of four cocoas with different processing histories

Cocoa and its constituent bioactives (particularly flavanols) have reported anti-diabetic and anti-obesity activities. One potential mechanism of action is inhibition of dipeptidyl peptidase-IV (DPP4), the enzyme that inactivates incretin hormones such as glucagon-like peptide-1 and gastric inhibitory peptide. The objective of this study was to determine the DPP4 inhibitory activities of cocoas with different processing histories, and identify processing factors and bioactive compounds that predict DPP4 inhibition. IC₂₅ values (μg mL^-1) were 4.82 for Diprotin A (positive control), 2135 for fermented bean extract, 1585 for unfermented bean extract, 2871 for unfermented liquor extract, and 1076 for fermented liquor extract This suggests mild inhibitory activity. Surprisingly, protein binding activity, total polyphenol, total flavanol, individual flavanol and complex fermentation/roasting product levels were all positively correlated to IC₂₅ concentrations (greater levels correspond to less potent inhibition). For the representative samples studied, fermentation appeared to improve inhibition. This study suggests that cocoa may possess mild DPP4 inhibitory activity, and that processing steps such as fermentation may actually enhance activity. Furthermore, this activity and the variation between samples were not easily explainable by traditional putative bioactives in cocoa. The compounds driving this activity, and the associated mechanism(s) by which this inhibition occurs, remain to be elucidated.