Gupta, A and Narkowicz, CK and Al-Aubaidy, HA and Jelinek, HF and Nichols, DS and Burgess, JR and Jacobson, GA, Phytosterol supplements do not inhibit dipeptidyl peptidase-4, Diabetes & Metabolic Syndrome: clinical research & reviews, 14 pp. 1475-1478. ISSN 1871-4021 (2020) [Refereed Article]
Copyright 2020 Elsevier Ltd.
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.
|Item Type:||Refereed Article|
|Keywords:||phytosterols, dipeptidyl peptidase-4, gas chromatography, in silico, in vitro, molecular docking, dipeptidyl peptidase-4 inhibitory assay, stigmasterol, b-Sitosterol, campesterol|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Pharmacology and pharmaceutical sciences|
|Research Field:||Basic pharmacology|
|Objective Group:||Clinical health|
|Objective Field:||Treatment of human diseases and conditions|
|UTAS Author:||Gupta, A (Mr Ankit Gupta)|
|UTAS Author:||Narkowicz, CK (Dr Christian Narkowicz)|
|UTAS Author:||Al-Aubaidy, HA (Dr Hayder Al-Aubaidy)|
|UTAS Author:||Nichols, DS (Dr David Nichols)|
|UTAS Author:||Burgess, JR (Professor John Burgess)|
|UTAS Author:||Jacobson, GA (Associate Professor Glenn Jacobson)|
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