Evaluation of Viburnum opulus L. Fruit Phenolics Cytoprotective Potential on Insulinoma MIN6 Cells Relevant for Diabetes Mellitus and Obesity

Abstract

In this study, the influence of guelder rose (Viburnum opulus) fruit fresh juice (FJ) and a phenolic-rich fraction (PRF) isolated from juice on mice insulinoma MIN6 cells activities was investigated. Extracts were able to decrease intracellular oxidative stress at the highest non-cytotoxic concentrations. They induced glucagon-like peptide-1 (GLP-1) secretion in the presence of an elevated glucose concentration, and they inhibited in vitro activity of the dipeptidyl peptidase-4 (DPP4) enzyme. Nonetheless, inhibition of glucose-stimulated insulin secretion was detected, which was accompanied by a decrease of cellular membrane fluidity and hyperpolarization effect. In addition, the increase of free fatty acid uptake and accumulation of lipid droplets in MIN6 cells were observed. Elevated extract concentrations induced cell apoptosis through the intrinsic mitochondrial pathway with activation of initiatory caspase-9 and downstream caspases-3/7. The fluorescence-quenching studies indicated that PRF extract has binding affinity to human serum albumin, which is one of the factors determining drug bioavailability. Taken together, despite the cytoprotective activity against generated intracellular oxidative stress, V. opulus revealed potential toxic effects as well as decreased insulin secretion from MIN6 cells. These findings are relevant in understanding V. opulus limitations in developing diet supplements designed for the prevention and treatment of postprandial glucose elevation.