Phytosterol supplements do not inhibit dipeptidyl peptidase-4

Background and aims: Several commercially available phytosterol supplements are promoted for their cholesterol-lowering effects. However, limited information is available about their potential antihyperglycaemic effects. This study aimed to evaluate the dipeptidyl peptidase-4 (DPP-4) inhibitory effects of phytosterol supplements in silico and in vitro to determine their potential for anti-diabetic activity.

Methods: Docking studies were carried out in silico to evaluate the potential for interactions between three major phytosterol compounds (stigmasterol, b-sitosterol, campesterol) and the DPP-4 enzyme, the enzyme that is inhibited by the anti-diabetic gliptins. Gas chromatographyetandem mass spectrometry (GC-MS/MS) was used to analyse three different supplements for phytosterol content. DPP-4 inhibitory activity was tested in vitro for these phytosterol supplements and two major phytosterol standards.

Results: In silico calculations predicted free binding energies for DPP-4 with the phytosterols to be: stigmasterol - 8.78 kcal/mol; b-sitosterol - 8.70 kcal/mol; campesterol - 8.40 kcal/mol. These binding energies indicated a potential for significant DPP-4 inhibition. However, these results were not supported by the in vitro studies. Stigmasterol and b-sitosterol had an IC₅₀ > 50 mg/ml (maximum tested concentration) and the Thompson’s Cholesterol Manager® and Mega Strength Beta Sitosterol® supplements gave an IC₅₀ > 100 mg/ml (maximum tested concentration). Blackmores Cholesterol Health® gave an IC₅₀ value of 40 mg/ml which was attributed to b-carotene content.

Conclusions: Phytosterol supplements do not appear to offer any anti-diabetic activity potential via pathways that involve the inhibition of DPP-4.