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.

Viburnum opulus L. Juice Phenolic Compounds Influence Osteogenic Differentiation in Human Osteosarcoma Saos-2 Cells

“…Specifically, potential synergic activities and chemical interactions may be responsible for the observed cellular effect. Still, the presented results are in agreement with our previous studies, where a phenolic rich fraction obtained from V. opulus was more active in Caco-2 and MIN-6 cells [24,30].…”

“…It may be suspected that V. opulus phenolics could directly react with intracellular free radical cations or could enhance the activity of the cellular detoxifying enzymes. As it was previously demonstrated, V. opulus treatment enhanced glutathione (GPx) peroxidase activity in insulinoma MIN6 cells [30]. Still, the observed decrease in intracellular ROS level was in accordance with detected ALP and RUNX2 elevation and matrix mineralization [49].…”

“…Therefore, the observed significant reduction in intracellular ROS is not related to antioxidant ability but confirmed PJ cytotoxic potential. In our previous studies on V. opulus fruit preparation activity, we observed comparable patterns of their influence-low doses of preparations were cytoprotective against cells, whereas increased triggered mitochondrial membrane depolarization decreased the ATP level and activated caspase 9 and, finally, apoptosis [30].…”

“…Thus, our effective dose of purified juice (25 mg/L) contained 16 mg/L chlorogenic acid. Additionally, V. opulus phenolics' binding affinity to human serum albumin may effectively regulate their bioavailability and cellular metabolism [22,30]. Data indicate that phenolic compounds, as well as chlorogenic acids, are metabolized by gut microbiota, and then their aglycons and other metabolites are absorbed in the small intestine by passive diffusion or with transporters [62].…”

Cicer arietinum L. Sprouts’ Influence on Mineralization of Saos-2 and Migration of MCF-7 Cells

“…The fluorescent signals at λ ex 485 nm and λ em 530 nm were analyzed. The negative control contained only cells in culture medium (with vehicle), while the positive control contained 500 µM tert -butylhydroperoxide ( t -BOOH) [ 52 , 53 ].…”