Anthocyanins protect human endothelial cells from mild hyperoxia damage through modulation of Nrf2 pathway

Abstract

The detrimental effects of high oxygen supplementation have been widely reported. Conversely, few is known about the effects of exposure to mild hyperoxic conditions, an interesting issue since the use of oxygenenriched mixture is now increasingly used in clinical practice and especially for professional and recreational reasons. Our study investigated if in vitro exposure of human umbilical vein endothelial cells (HUVECs) to moderate hyperoxia (O 2 32 %) induces cellular alterations, measured as changes in cell signaling pathways. Furthermore, by means of an ex vivo experimental model where human volunteers were used as bioreactors, we studied whether anthocyanin metabolites are able to protect HUVECs against mild hyperoxia-induced damage. We observed that the cytotoxic effect of mild hyperoxia came along with a significant decrease in nuclear accumulation of the transcription factor Nrf2, as well as in the expression of Nrf2-regulated antioxidant and cytoprotective genes. Furthermore, under normoxic conditions, anthocyanin metabolites appeared able to activate the Nrf2 pathway, through the involvement of specific kinases (ERK1/2); this adaptive effect may explain the protective effect observed in mild hyperoxia-exposed HUVECs following anthocyanin pretreatment. This study confirms that dietary anthocyanins and/or their metabolites can protect endothelial cells against mild hyperoxia-induced alterations acting as cell signaling modulators.

Cyanidin-3-O -glucoside counters the response to TNF-alpha of endothelial cells by activating Nrf2 pathway

“…Moreover, treatment with C3G alone lead to an increase of GSH levels, supporting the hypothesis that it can induce “per se” an adaptive cell response associated with an increased reducing intracellular capacity, as seen for SOD activity. These data are in agreement with other reports, suggesting that specific flavonoids induce an increase of cellular antioxidant activity, and that such capability is the main property of these biocompounds .…”

“…Similarly, in accordance with our findings, other studies have demonstrated that pharmacological activation of Nrf2 transcription factor by different phenolic compounds (e.g., sulforaphane) induces antiatherogenic effects in vascular endothelium by suppressing inflammation [37]. Furthermore, in HUVECs, anthocyanin metabolites appeared able to activate Nrf2 pathway, through the involvement of ERK1/2 eliciting a protective effect in endothelium exposed to mild hyperoxia [27]. In our experiments, as consequence of Nrf2 activation, HO-1 and NQO-1 expression were upregulated following C3G pretreatment; this effect was present both in cells exposed or not to TNF-␣ (Fig.…”

Palmitate-induced endothelial dysfunction is attenuated by cyanidin-3-O-glucoside through modulation of Nrf2/Bach1 and NF-κB pathways

“…The pretreatment with C3G was able, in a dose-dependent way, to significantly protect HUVECs from PA-induced toxicity. C3G, at the tested concentrations, and WEL alone did not affect cell viability, as reported elsewhere (Anwar et al, 2014;Cimino et al, 2013;Speciale et al, 2013). It is interesting that, at similar doses, in cultured…”

The role of Nrf2 in oxidative stress-induced endothelial injuries

“…Increased Nrf2 activity and improved mitochondrial function may both bolster its positive effects (MartinMontalvo et al 2011). Cimino et al (2013) reported that anthocyanins protect human endothelial cells from mild hyperoxic damage via the modulation of the Nrf2 pathway. Tea flavonoids also protect endothelial cells against inflammation by inhibiting AhR and activating Nrf2-regulated genes (Han et al 2012).…”