Resvega, a Nutraceutical Preparation, Affects NFκB Pathway and Prolongs the Anti-VEGF Effect of Bevacizumab in Undifferentiated ARPE-19 Retina Cells

Abstract

Age-related macular degeneration (AMD) is an irreversible chronic degenerative pathology that affects the retina. Despite therapeutic advances thanks to the use of anti-vascular endothelial growth factor (VEGF) agents, resistance mechanisms have been found to accentuate the visual deficit. In the present study, we explored whether a nutraceutical formulation composed of omega-3 fatty acids and resveratrol, called Resvega®, was able to disrupt VEGF-A secretion in human ARPE-19 retina cells. We found that Resvega® inhibits VEGF-A secretion through decreases in both the PI3K-AKT-mTOR and NFκB signaling pathways. In NFκB signaling pathways, Resvega® inhibits the phosphorylation of the inhibitor of NFκB, IκB, which can bind NFκB dimers and sequester them in the cytoplasm. Thus, the NFκB subunits cannot migrate to the nucleus where they normally bind and stimulate the transcription of target genes such as VEGF-A. The IκB kinase complex (IKK) is also affected by Resvega® since the nutraceutical formulation decreases both IKKα and IKKβ subunits and the IKKγ subunit which is required for the stimulation of IKK. Very interestingly, we highlight that Resvega® could prolong the anti-angiogenic effect of Avastin®, which is an anti-VEGF agent typically used in clinical practice. Our results suggest that Resvega® may have potential interest as nutritional supplementation against AMD.

The Essential Role of Light-Induced Autophagy in the Inner Choroid/Outer Retinal Neurovascular Unit in Baseline Conditions and Degeneration

“…This is confirmed by using the natural autophagy activator resveratrol, which inhibits Epidermal Growth Factor precursor homology domain A (EGF-A) via suppression of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)-mTOR and Nuclear Factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling pathways. In detail, resveratrol inhibits the phosphorylation of the inhibitor of nuclear factor kappa B (IκB), which inhibits NF-κB [76]. In this way NF-κB cannot migrate any longer to the nucleus, where it stimulates the transcription of VEGF-A [76].…”

“…In detail, resveratrol inhibits the phosphorylation of the inhibitor of nuclear factor kappa B (IκB), which inhibits NF-κB [76]. In this way NF-κB cannot migrate any longer to the nucleus, where it stimulates the transcription of VEGF-A [76]. Similarly, the natural autophagy activator berberin inhibits the expression of VEGF from retinal endothelial cells via its action on the AKT/mTOR pathway [77].…”

CX3CL1/CX3CR1 Signaling Mediated Neuroglia Activation Is Implicated in the Retinal Degeneration: A Potential Therapeutic Target to Prevent Photoreceptor Death

“… 96 Moreover, Resvega can inhibit the VEGF-A secretion through and mitigate apoptosis of ARPE-19 cell lines through modulating NF-κB signaling. 97 In this study, we show that CX3CL1/CX3CR1 signaling promotes the release of IL-1β and TNF-α through the phosphorylation of NF-κB. Moreover, AZD8797 can inhibit the phosphorylation of NF-κB, and alleviate the inflammatory response.…”

Anti(angiogenic) food components: can be a major source of bias in the investigation of angiogenesis inhibitors

“…Omega-3-PUFAs and other vitamins, similar considerations apply to other natural angiogenesis inhibitors like omega-3-PUFAs ( 74 ) which has been shown to reduce pathological retinal angiogenesis ( 75 ), age-related macular degeneration ( 76 ), colon cancer ( 77 ), breast cancer ( 78 ), and neuroblastoma ( 79 ).…”