Chicoric acid ameliorates palmitate-induced sphingosine 1-phosphate signaling pathway in the PBMCs of patients with newly diagnosed type 2 diabetes.

Abstract

Sphingosine 1-phosphate (S1P) signaling pathway is involved in the pathogenesis of type 2 diabetes (T2D). So, targeting S1P signaling pathway could be considered as potential therapeutic target for T2D. The aim of this study was to investigate the effects of palmitate and chicoric acid (CA) on S1P signaling pathway in peripheral blood mononuclear cells (PBMCs) from newly diagnosed patients with T2D. 20 newly diagnosed patients with T2D, aged 40-60 years, were enrolled in the study. PBMCs were isolated and then treated as follows: control groups (untreated, treated with BSA 1% for 12h), CA groups (treated with 50 μM CA for 6h), palmitate groups (treated with 500 μM palmitate for 12h), palmitate + CA groups (treated with 500 μM palmitate for 12h and then treated with 50 μM CA for 6h). Finally, sphingosine kinase 1 (SPHK1) and sphingosine 1-phosphate receptor 1 (S1PR1) genes expression were evaluated by real-time PCR and S1PR1 protein levels were quantified using ELISA. Palmitate significantly increased SPHK1 and S1PR1 genes expression and S1PR1 protein levels in PBMCs of patients with diabetes. However, CA ameliorates palmitate-increased SPHK1 and S1PR1 genes expression and S1PR1 levels in these cells. These data indicate that CA could be considered as a novel S1P signaling pathway inhibitor through down regulation of SPHK1 and S1PR1.