The Impact of O-Glycosylation on Cyanidin Interaction with RBCs and HMEC-1 Cells-Structure⁻Activity Relationships.

Sylwia Cyboran-Mikołajczyk,Karolina Matczak,Natalia Glatzel-Plucińska,Katarzyna Solarska-Ściuk,Katarzyna Mieszała,Halina Kleszczyńska

doi:10.3390/ijms20081928

Abstract

With the aim of contributing to the knowledge about their potential therapeutic activity, we determined the biological activities of cyanidin and its selected O-glycosides in relation to erythrocytes (RBCs) and human dermal vascular endothelial cells (HMEC-1). Furthermore, on the basis of changes in the physical/functional properties of the cells, the structure–activity relationships of the compounds were determined. Concerning erythrocytes, we analyzed the antioxidant activity of the compounds and their impact on the RBCs’ shape and transmembrane potential. The compounds’ cytotoxic activity, ability to modulate apoptosis, cell cycle, and intracellular ROS generation, as well as inhibitory activity against AAPH-inducted oxidative stress, were determined in relation to HMEC-1 cells. We demonstrated that biological activity of cyanidin and its O-glycosides strongly depends on the number and type of sugar substituents, and varies depending on the extracellular environment and type of cells. The compounds are practically non-cytotoxic, and do not induce apoptosis or disturb the progression of the cell cycle. Additionally, the compounds alter the shape of RBCs, but they do not affect their transmembrane potential. They effectively protect erythrocytes against free radicals and affect intracellular reactive oxygen spices (ROS) generation under physiological and AAPH-induced oxidative stress conditions. Our results suggest a potential beneficial effect of cyanidin on the cardiovascular system.

Highlights

Cyanidin and its glycosides occur practically in all colored plants, especially in fruit, vegetables, and flowers
Prior to assessing the biological activity of the compounds and in order to assess their ability to inhibit cell viability, XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) and Hoechst 33324 (2,5 -bi-1H-benzimidazole, 2 -(4-ethoxyphenyl)-5-(4-methyl-1-piperazinyl)) assays were performed to exclude the possibility of cytotoxicity
For the highest concentration of 100 μM, only CDG showed a protective effect against AAPH-induced oxidative stress. These results indicate that 3-O-glycosylation and 3-5-di-glycosylation increase aglycone’s ability to scavenge intracellular reactive oxygen spices (ROS) generated by AAPH

Summary

Introduction

Cyanidin and its glycosides occur practically in all colored plants, especially in fruit, vegetables, and flowers. Cyanidin as an aglycon (anthocyanidins) possesses two benzene rings, A and B, and a heterocyclic ring C, which form the C6-C3-C6 system It contains five hydroxyl groups: At C3 and C4 positions of the B ring, C7 and C5 of the A ring, and at C3 of the heterocyclic C ring (Table 1). Basic studies are needed in order to establish the molecular mechanism responsible for their beneficial effect on human health. Such an approach allows one to indicate the most effective substances in the prevention and treatment of many pathological conditions

Methods

Results

Conclusion