Modulation of NF-κB activation by resveratrol in LPS treated human intestinal cells results in downregulation of PGE2 production and COX-2 expression

Cianciulli, Antonia; Calvello, Rosa; Cavallo, Pasqua; Dragone, Teresa; Carofiglio, Vito Emanuele; Panaro, Maria Antonietta

doi:10.1016/j.tiv.2012.06.015

Cited by 80 publications

(65 citation statements)

References 31 publications

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“…Além disso, já foi reportado que o resveratrol pode bloquear a fosforilação da subunidade p65 do NF-kB, inibindo sua translocação para o núcleo e, consequentemente, sua ação nos genes. Este bloqueio estaria correlacionado com a inibição da fosforilação e degradação do IkBá pelo resveratrol (Cianciulli et al, 2012). Csiszar et al (2006) demonstraram em células endoteliais de artéria coronariana a inibição da expressão da IL-6, iNOS, ICAM-1, VCAM-1, bem como a menor ativação do NF-kB (mais de 50%) pelo resveratrol.…”

Section: Mecanismos Moleculares De Ação De Polifenóis De Uvas E Vinhounclassified

“…Ademais, já foi demonstrada in vitro a capacidade do resveratrol em inibir as enzimas lipoxigenase (Chatterjee et al, 2011) e cicloxigenase (Cianciulli et al, 2012), as quais atuam na síntese de eicosanóides a partir do ácido araquidônico. Leifert & Abeywardena (2008) demonstraram em células Caco-2 e HepG2 a capacidade de extratos de vinho tinto e de sementes de uva em inibirem a atividade da 5-lipoxigenase.…”

Section: Mecanismos Moleculares De Ação De Polifenóis De Uvas E Vinhounclassified

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Mecanismos moleculares de ação anti-inflamatória e antioxidante de polifenóis de uvas e vinho tinto na aterosclerose

Séfora-Sousa

Angelis-Pereira

2013

Rev. bras. plantas med.

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RESUMO:Este trabalho visa investigar os possíveis mecanismos moleculares de ação dos polifenóis de uvas e vinho tinto contra os processos oxidativos e inflamatórios envolvidos na aterosclerose. Trata-se de um estudo de revisão de literatura realizado por meio de buscas nas bases de dados PubMed e ScienceDirect utilizando os seguintes descritores: vinho tinto, uva, polifenóis, resveratrol, aterosclerose, LDL-oxidada, inflamação, estresse oxidativo, NF-kB, AP-1, Nrf2, SIRT-1, MicroRNA. Embora tais mecanismos ainda não estejam totalmente esclarecidos, os estudos indicam que compostos fenólicos presentes em uvas podem se complexar com metais (como ferro e cobre) que provocam peroxidação dos lipídios, aumentam a atividade antioxidante do plasma, associam-se com a LDL-c aumentando sua resistência à oxidação, preservam a atividade da enzima paraoxonase, neutralizam radicais livres, e ativam fatores de transcrição como o Nrf2, que aumenta a expressão de genes que codificam proteínas importantes na defesa antioxidante, como a superóxido dismutase e a glutationa peroxidase. Além disso, os polifenóis inibem a fosforilação de MAP quinases, inibindo assim os fatores de transcrição NF-kB e AP-1 e, consequentemente, reduzindo a síntese do TNF-á, interleucinas, moléculas de adesão e quimiocinas. Também inibem a atividade das enzimas cicloxigenase e lipoxigenase. Outro mecanismo proposto é a ação do resveratrol sobre a atividade de deacetilases de histonas, como a SITR-1. Estas ações em conjunto reduzem a oxidação da LDL-c e o processo inflamatório, atenuando o processo aterogênico. Palavras-chave:Resveratrol, LDL-c, Nrf2, NF-kB, AP-1, aterosclerose.ABSTRACT: Molecular mechanisms of action of grape and red wine polyphenols against oxidative and inflammatory processes in atherosclerosis. This study aimed to investigate the possible molecular mechanisms of action of grape and red wine polyphenols against oxidative and inflammatory processes in atherosclerosis. This is a literature review performed by searching in the PubMed and ScienceDirect databases using the following descriptors: red wine, grape, polyphenols, resveratrol, atherosclerosis, oxidized LDL, inflammation, oxidative stress, NF-kB, AP-1, Nrf2, SIRT-1, MicroRNA. Although the mechanisms are not fully understood, studies indicate that phenolic compounds possibly complex with metals (such as iron and copper), or else they increase the antioxidant activity of plasma and also preserve the activity of enzyme paraoxonase. Moreover, the polyphenols neutralize free radicals and activate transcription factors, for example Nrf2, which increases the expression of genes that encode important proteins in antioxidant defense (such as superoxide dismutase and glutathione peroxidase). Additionally, polyphenols inhibit the phosphorylation of MAP kinases, causing a blocking effect on the transcription factors NF-kB and AP-1 and, consequently, blocking the synthesis of TNF-α, interleukins, chemokines and molecules adhesion. Moreover, it can inhibit the activity of the cycloxygenase and li...

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Section: Mecanismos Moleculares De Ação De Polifenóis De Uvas E Vinhounclassified

Mecanismos moleculares de ação anti-inflamatória e antioxidante de polifenóis de uvas e vinho tinto na aterosclerose

Séfora-Sousa

Angelis-Pereira

2013

Rev. bras. plantas med.

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“…With dextran sodium sulfate (DSS) treatment, COX-2 potentially increases 2.3-fold [30] which can be attenuated by Resveratrol [13,17,18,24,25,28] both directly and through suppressed ROS levels [31]. The effects of resveratrol supplementation on COX-1 have been equivocal; one study showed no significant changes in COX-1[25] while others showed COX-1 was decreased [18,24].…”

Section: Reduced Proinflammatory Mediatorsmentioning

confidence: 99%

“…With resveratrol supplementation, NF-κB p65 subunit activity is inhibited through attenuating attenuate nuclear factor of kappa B inhibitor, alpha (IκBα) phosphorylation, IκB kinase beta (IKKβ) activation, extracellular signal-regulated kinases (ERK) phosphorylation, signal transducer and activator of transcription 3 (STAT3) activation and NF-κB DNA binding in animal models [16][17][18]. Resveratrol also amplifies silent mating type information regulation 1 (SIRT1) gene expression, [18,19] which indirectly inhibitsNF-κB.…”

Section: Introductionmentioning

confidence: 99%

Effects of Resveratrol on Inflammatory Bowel Disease: A Review

Abouaf-Tabet¹,

Kolkhorst²,

Hong

2014

JNHFS

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“…This over-production of ROS may cause tissue injury by damaging membrane structures through lipid peroxidation. 12 LPS is recognized by the Toll-like receptor (TLR)-4, a proinflammatory cell surface receptor that is expressed on cells of the innate immune system as well as epithelial cells. Thus, free radicals are key-mediators that initiate or promote inflammation and consequently, their neutralization by dietary compounds may help to attenuate inflammation.…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory activity of polyphenolics from açai (Euterpe oleracea Martius) in intestinal myofibroblasts CCD-18Co cells

et al. 2015

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The demand for tropical fruits high in polyphenolics including açai (Euterpe oleracea Mart.) has been increasing based on ascribed health benefits and antioxidant properties. This study evaluated the anti-inflammatory activities of açai polyphenolics in human colon myofibroblastic CCD-18Co cells to investigate the suppression of reactive oxygen species (ROS), and mRNA and protein expression of inflammatory proteins. Non-cytotoxic concentrations of açai extract, 1-5 mg gallic acid equivalent L(-1), were selected. The generation of ROS was induced by lipopolysaccharide (LPS) and açai extract partially reversed this effect to 0.53-fold of the LPS-control. Açai extract (5 mg GAE L(-1)) down-regulated LPS-induced mRNA-expression of tumor necrosis factor alpha, TNF-α (to 0.42-fold), cyclooxygenase 2, COX-2 (to 0.61-fold), toll-like receptor-4, TLR-4 (to 0.52-fold), TNF receptor-associated factor 6, TRAF-6 (to 0.64-fold), nuclear factor kappa-B, NF-κB (to 0.76-fold), vascular cell adhesion molecule 1, VCAM-1 (to 0.71-fold) and intercellular adhesion molecule 1, ICAM-1 (to 0.68-fold). The protein levels of COX-2, TLR-4, p-NF-κB and ICAM-1 were induced by LPS and the açai extract partially reversed this effect in a dose-dependent manner. These results suggest the anti-inflammatory effect of açai polyphenolic extract in intestinal cells are at least in part mediated through the inhibition of ROS and the expression of TLR-4 and NF-κB. Results indicate the potential for açai polyphenolics in the prevention of intestinal inflammation.

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Modulation of NF-κB activation by resveratrol in LPS treated human intestinal cells results in downregulation of PGE2 production and COX-2 expression

Cited by 80 publications

References 31 publications

Mecanismos moleculares de ação anti-inflamatória e antioxidante de polifenóis de uvas e vinho tinto na aterosclerose

Mecanismos moleculares de ação anti-inflamatória e antioxidante de polifenóis de uvas e vinho tinto na aterosclerose

Effects of Resveratrol on Inflammatory Bowel Disease: A Review

Anti-inflammatory activity of polyphenolics from açai (Euterpe oleracea Martius) in intestinal myofibroblasts CCD-18Co cells

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