Low nanomolar caffeic acid attenuates high glucose‐induced endothelial dysfunction in primary human umbilical‐vein endothelial cells by affecting NF‐κB and Nrf2 pathways

Fratantonio, Deborah; Speciale, Antonio; Canali, Raffaella; Natarelli, Lucia; Ferrari, Daniela; Saija, Antonella; Virgili, Fabio; Cimino, Francesco

doi:10.1002/biof.1312

Cited by 50 publications

(38 citation statements)

References 39 publications

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“…decreases the gLDL-induced secretion of CRP, in good agreement with published data showing that coffee consumption is associated with lower CRP levels in plasma of diabetic or obese women [22,23]. Moreover, CAF decreases the secretion of VCAM-1 and MCP-1 induced by gLDL in HEC, the results confirming previous data showing that CAF decreases inflammation in HEC incubated with resistin or high glucose or in a hyperhomocysteinemia in vivo model by attenuating NF-kB signaling [24][25][26]. We have previously shown that the secretion of VCAM-1 and MCP-1 is stimulated in gLDL-exposed HEC by Caffeic acid decreases oxidative stress in gLDL-exposed HEC.…”

Section: Discussionsupporting

confidence: 91%

Caffeic acid attenuates the inflammatory stress induced by glycated LDL in human endothelial cells by mechanisms involving inhibition of AGE‐receptor, oxidative, and endoplasmic reticulum stress

et al. 2017

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Type 2 diabetes mellitus is a worldwide epidemic and its atherosclerotic complications determine the high morbidity and mortality of diabetic patients. Caffeic acid (CAF), a phenolic acid present in normal diets, is known for its antioxidant properties. The aim of this study was to investigate CAF's anti-inflammatory properties and its mechanism of action, using cultured human endothelial cells (HEC) incubated with glycated low-density lipoproteins (gLDL). Levels of the receptor for advanced glycation end-products (RAGE), inflammatory stress markers (C reactive protein, CRP; vascular cell adhesion molecule-1, VCAM-1; monocyte chemoattractant protein-1, MCP-1), and oxidative stress and endoplasmic reticulum stress (ERS) markers were evaluated in gLDL-exposed HEC, in the presence/absence of CAF. RAGE silencing or blocking, specific inhibitors for oxidative stress (apocynin, N-acetyl-cysteine), and ERS (salubrinal) were used. The results showed that: (i) gLDL induced CRP synthesis and secretion through mechanisms involving NADPH oxidase-dependent oxidative stress and ERS in HEC; (ii) gLDL-RAGE interaction, oxidative stress, and ERS stimulated the secretion of VCAM-1 and MCP-1 in HEC; and (iii) CAF reduced the secretion of CRP, VCAM-1, and MCP-1 in gLDL-exposed HEC by inhibiting RAGE expression, oxidative stress, and ERS. In conclusion, CAF might be a promising alternative to ameliorate a wide spectrum of disorders due to its complex mechanisms of action resulting in anti-inflammatory and antioxidative properties. © 2017 BioFactors, 43(5):685-697, 2017.

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Section: Discussionsupporting

confidence: 91%

Caffeic acid attenuates the inflammatory stress induced by glycated LDL in human endothelial cells by mechanisms involving inhibition of AGE‐receptor, oxidative, and endoplasmic reticulum stress

et al. 2017

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“…However, recent evidences suggest that the selective inhibition of NF‐κB pathway and the activation of an antioxidant adaptive cell response through nuclear factor erythroid 2 (Nrf2) pathway modulation seem to be the main mechanisms by which ACNs can exert their protective effect. In fact, previous data supported the hypothesis of a cross talk between Nrf2 and NF‐κB and particularly of an inhibitory effect of Nrf2/EpRE (Electrophile‐Responsive Element) pathway on NF‐κB transcription machinery (Ferrari et al, ; Fratantonio et al, ; Fratantonio, Speciale, et al, ; Fratantonio, Cimino, Speciale, & Virgili, ; Speciale et al, ).…”

Section: Discussionmentioning

confidence: 66%

Anthocyanins ameliorate palmitate‐induced inflammation and insulin resistance in 3T3‐L1 adipocytes

Muscarà

Molonia

Speciale

et al. 2019

Phytotherapy Research

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Increased adiposity has been associated with adipose tissue low‐grade inflammation leading to insulin resistance. Adipocyte differentiation inhibitors are expected to be effective in preventing obesity and related diseases. Anthocyanins (ACNs) are associated to enhanced adipocyte function and protection from metabolic stress. Herein, we evaluated the in vitro protective effects of an ACN rich extract against palmitic acid (PA)‐induced hypertrophy, inflammation, and insulin resistance in 3T3‐L1 adipocytes. ACN extract pretreatment reduces lipid accumulation and peroxisome proliferators‐activated receptor‐γ protein levels induced by PA. In addition, PA induces inflammation with activation of NF‐κB pathway, whereas ACN extract pretreatment dose‐dependently inhibited this pathway. Furthermore, adipocyte dysfunction associated with hypertrophy induces insulin resistance by affecting phosphatidylinositol 3‐kinase‐protein kinase B/Akt axis, GLUT‐1, and adiponectin mRNA levels. ACN extract pretreatment reverts these effects induced by PA and moreover was able to induce insulin pathway with levels higher than insulin control cells, supporting an insulin sensitizer role for ACNs. This study demonstrates a prevention potential of ACNs against obesity comorbidities, due to their protective effects against inflammation/insulin resistance in adipocytes. In addition, these results contribute to the knowledge and strategies on the evaluation of the mechanism of action of ACNs from a food source under basal and insulin resistance conditions related to obesity.

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“…Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and 18S rRNA were validated as reference genes and they maintained constant expression levels in all conditions and treatments. The specific primers set for the target genes were as follows: 18S rRNA, forward, 5′-GTA ACC CGT TGA ACC CCA TT-3′, reverse, 5′-CCA TCC AAT CGG TAG TAG CG-3′ [16]; GAPDH, forward, 5′-GGC TCT CCA GAA CAT CAT CCC TGC-3′, reverse, 5′-GGG TGT CGC TGT TGA AGT CAG AGG-3′; E-selectin, forward, 5′-CTG CCA AGT GGT AAA ATG TTC AAG-3′, reverse, 5′-TTG GAC TCA GTG GGA GCT TCA-3′ [17]; VCAM-1, forward, 5′-GAA TGG GAG CTC TGT CAC TGT AAG C-3′, reverse, 5′-GAC CAA GAC GGT TGT ATC TCT GGG-3′ [18]; TNF- α , forward, 5′-CCA GGC AGT CAG ATC ATC TTC TC-3′, reverse, 5′-AGC TGG TTA TCT CTC AGC TCC AC-3′ [19]; IL-8, forward, 5′-ACT GAG AGT GAT TGA GAG TGG AC-3′, reverse, 5′-AAC CCT CTG CAC CCA GTT TTC-3′ (Primers Bank ID 10834978a2) [20]. Gene expression was assessed by real-time PCR (Applied Biosystem 7300 Real-Time PCR System, Monza, Italy) coupled with the Sybr green JumpStart™ Taq ReadyMix kit.…”

Section: Methodsmentioning

confidence: 99%

Cyanidin-3-O-Glucoside Modulates the In Vitro Inflammatory Crosstalk between Intestinal Epithelial and Endothelial Cells

Ferrari

Cimino

Fratantonio

et al. 2017

Mediators of Inflammation

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Intestinal epithelium represents a protective physical barrier and actively contributes to the mucosal immune system. Polarized basolateral intestinal secretion of inflammatory mediators, followed by activation of NF-κB signaling and inflammatory pathways in endothelial cells, efficiently triggers extravasation of neutrophils from the vasculature, therefore contributing to the development and maintenance of intestinal inflammation. Proper regulation of NF-κB activation at the epithelial interface is crucial for the maintenance of physiological tissue homeostasis. Many papers reported that anthocyanins, a group of compounds belonging to flavonoids, possess anti-inflammatory effects and modulate NF-κB activity. In this study, by using a coculture in vitro system, we aimed to evaluate the effects of TNF-α-stimulated intestinal cells on endothelial cells activation, as well as the protective effects of cyanidin-3-glucoside (C3G). In this model, TNF-α induced nuclear translocation of NF-κB and TNF-α and IL-8 gene expression in Caco-2 cells, whereas C3G pretreatment dose-dependently reduced these effects. Furthermore, TNF-α-stimulated Caco-2 cells induced endothelial cells activation with increased E-selectin and VCAM-1 mRNA, leukocyte adhesion, and NF-κB levels in HUVECs, which were inhibited by C3G. We demonstrated that selective inhibition of the NF-κB pathway in epithelial cells represents the main mechanism by which C3G exerts these protective effects. Thus, anthocyanins could contribute to the management of chronic gut inflammatory diseases.

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Low nanomolar caffeic acid attenuates high glucose‐induced endothelial dysfunction in primary human umbilical‐vein endothelial cells by affecting NF‐κB and Nrf2 pathways

Cited by 50 publications

References 39 publications

Caffeic acid attenuates the inflammatory stress induced by glycated LDL in human endothelial cells by mechanisms involving inhibition of AGE‐receptor, oxidative, and endoplasmic reticulum stress

Caffeic acid attenuates the inflammatory stress induced by glycated LDL in human endothelial cells by mechanisms involving inhibition of AGE‐receptor, oxidative, and endoplasmic reticulum stress

Anthocyanins ameliorate palmitate‐induced inflammation and insulin resistance in 3T3‐L1 adipocytes

Cyanidin-3-O-Glucoside Modulates the In Vitro Inflammatory Crosstalk between Intestinal Epithelial and Endothelial Cells

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