Anthocyanins Found in Pinot Noir Waste Induce Target Genes Related to the Nrf2 Signalling in Endothelial Cells

Abstract

Grape pomace is a source of anthocyanins, which can prevent cardiovascular diseases due to their antioxidant properties. Anthocyanin activity is associated with the ability to regulate oxidative stress through the transcription factor Nrf2. Thus, the present study aimed to evaluate if the anthocyanins found in Pinot noir pomace extract can affect the target genes related to the Nrf2 signalling pathway in endothelial cells. Our results highlight that the predominant anthocyanin in the Pinot noir pomace extract was malvidin-3-glucoside (3.7 ± 2.7 Eq. Malv-3-glu/kg). Molecular docking indicated that cyanidin-3-glucoside (−6.9 kcal/mol), malvidin-3-glucoside (−6.6 kcal/mol) and peonidin-3-glucoside (−6.6 kcal/mol) showed the highest affinities for the binding sites of the BTB domains in Keap1, suggesting that these components may modify the interaction of this protein with Nrf2. In addition, when HUVEC cells were exposed to different concentrations of Pinot noir pomace extract (100 µg/mL, 200 µg/mL, and 400 µg/mL), no changes in Nrf2 gene expression were observed. However, the gene expression of HO-1 and NQO1, which are in the signalling pathway of this transcription factor, increased according the concentrations of the extract (p = 0.0004 and p = 0.0084, respectively). In summary, our results show that anthocyanins play a very important role in Nrf2 activation and release, while at the same time not promoting its transcription. These preliminary results strongly suggest that the Pinot noir pomace extract can serve as a potent bioactive component source that protects cells against oxidative stress.

Contribution of macro- and micronutrients intake to gastrointestinal cancer mortality in the ONCONUT cohort: Classical vs. modern approaches

“…Alcohol consumption had a protective role on mortality in our cohort, unlike in the literature ( 43 ), probably due to wine consumption rather than spirits. Red wine is a source of polyphenols, such as resveratrol and anthocyanin, with demonstrated antioxidant properties and protective role against cardiovascular diseases ( 44 – 46 ).…”

Antioxidant Phytochemicals as Potential Therapy for Diabetic Complications

“…Furthermore, BAE, malvidin, and glucosides inhibited VEGF, ICAM, and NF-κB expression [216]. Malvidin-3-glucoside and other anthocyanins in grape pomace were suggested to modify KEAP1/Nrf2 interaction and increase the expression of HO-1 and NQO1 antioxidants [217]. This suggests that malvidin-3-glucoside and the likes inhibit inflammation in endothelial cells by improving antioxidant enzymatic expression via Nrf2 signaling-dependent mechanisms.…”

Activation of Nrf2 signaling: A key molecular mechanism of protection against cardiovascular diseases by natural products

“…Studies have revealed that SFN, rutin and curcumin can inhibit the ability of the Cullin3-Rbx1 E3 ubiquitin ligase complex via modifying Keap1 Cys151 residue, resulting in Nrf2 activation to protect against myocardial injury in mice ( Takaya et al, 2012 ; Sthijns et al, 2017 ; Shin et al, 2020 ). Similarly, data of molecular docking indicates that the BTB domains in Keap1-Nrf2 complex directly bound the cyanidin-3-glucoside (−6.9 kcal/mol), malvidin-3-glucoside (−6.6 kcal/mol) and peonidin-3-glucoside (−6.6 kcal/mol), which are the major active compound of glycosylated anthocyanins ( Herrera-Bravo et al, 2022 ). Apart from that, a number of bioactive compounds including withaferin A, xanthohumol and betanin can modify cysteine residues, specifically Cys151, Cys273 and Cys288, through interaction with their sulfhydryl groups, allowing the cleavage of the Keap1-Nrf2 interaction inducing antioxidant proteins and phase II detoxification enzymes ( Yao et al, 2015 ; Heyninck et al, 2016 ; Silva et al, 2022 ).…”

“…Knockdown of Nrf2 abolishes these effects and exacerbates ox LDL-induced oxidative damage in HUVECs ( Hou et al, 2021 ). Anthocyanin in plants promotes Nrf2 activation and release in a concentration-dependent manner, leading to increased HO-1 and NQO1 expression in HUVECs under hyperoxia ( Cimino et al, 2013 ; Herrera-Bravo et al, 2022 ). Cyanidin-3-O-glucoside, another type of anthocyanin, induces nuclear localization of Nrf2 and activation of cellular antioxidant and cytoprotective genes in palmitate or TNF-α-induced HUVECs ( Speciale et al, 2013 ; Fratantonio et al, 2015 ).…”