Delphinidin and cyanidin inhibit PDGF_AB‐induced VEGF release in vascular smooth muscle cells by preventing activation of p38 MAPK and JNK

Abstract

Background and purpose: Red wine polyphenols (RWPs) inhibit the expression of vascular endothelial growth factor (VEGF), a major pro-angiogenic and pro-atherosclerotic factor, in vascular smooth muscle cells (VSMCs). The aim of this study was to identify which red wine polyphenols were inhibitory and to determine the mechanism underlying the inhibitory effects. Experimental approach: Release of VEGF stimulated by platelet derived growth factor AB (PDGF AB ) , from human aortic VSMCs was measured by immunoassay and phosphorylation of kinases by Western blot analysis. The direct antioxidant properties of polyphenols were determined by electron paramagnetic resonance and the cellular formation of reactive oxygen species (ROS) by dichlorofluorescein. Key results: The inhibitory effect of RWPs on PDGF AB -induced release of VEGF was mimicked by delphinidin but not by quercetin, catechins, resveratrol, gallic acid or caffeic acid. In the anthocyanin class, not only delphinidin but also cyanidin prevented VEGF release whereas malvidin and peonidin were without effect. RWPs, delphinidin and cyanidin directly scavenged ROS and prevented the PDGF AB -induced formation of ROS in VSMCs. Malvidin and peonidin did not scavenge ROS but prevented the cellular formation of ROS. Although the p38 MAPK, ERK1/2 and JNK pathways have been involved in the PDGF AB -induced expression of VEGF, in our experiments, only phosphorylation of p38 MAPK and JNK was inhibited by RWPs, delphinidin and cyanidin. Conclusions and implications: Anthocyanins presenting a hydroxyl residue at position 3 0 are able to inhibit PDGF AB -induced VEGF expression by preventing activation of p38 MAPK and JNK in VSMCs.

Anti‑inflammatory effect of delphinidin on intramedullary spinal pressure in a spinal cord injury rat model

“…The results of the present study demonstrated that the anti-inflammatory effect of delphinidin reduced the p-p38-MAPK protein expression and caspase-3 activity in a rat model of SCI. Furthermore, Oak et al (30) reported that delphinidin prevents the activation of p38-MAPK and JNK in vascular smooth muscle cells. Overall, these data suggest that administration of delphinidin alleviates the SCI-induced inflammation through suppression of the p38-MAPK signaling pathway.…”

Delphinidin inhibits cell proliferation and invasion via modulation of Met receptor phosphorylation

“…A compound with four hydroxyl groups (3, 3′, 4′ and 5′), delphinidin has recently been shown to be a potent inhibitor of vascular endothelial growth factor receptor activity (Lamy et al, 2006). The presence of vicinal hydroxyl substituents on the B-ring of delphinidin seems to be crucial for interaction with EGFR, as tyrosine kinase activity associated with this cell surface receptor is inhibited by delphinidin in human breast cancer cells (Oak et al, 2006). This is significant as inhibition of downstream effectors of the activated receptors by delphinidin may disturb vital biological cues and hinder the progression of carcinogenesis.…”

Cyanidin Protects SH-SY5Y Human Neuroblastoma Cells from 1-Methyl-4-Phenylpyridinium-Induced Neurotoxicity

“…Cyanidin is demonstrated to be beneficial against diabetes [4,5], cancer [6][7][8], and atherosclerosis [9]. In the central nervous system, recent investigations indicate that cyanidin showed potential protections against Alzheimer's disease and multiple sclerosis [10,11].…”