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Int J Mol Sci ; 18(7)2017 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-28672844

RESUMO

Several metabolomics of polymeric flavan-3-ols have reported that proanthocyanidins are extensively metabolized by gut microbiota. 5-(3',4'-dihydroxyphenyl)-γ-valerolactone (DHPV) has been reported to be the major microbial metabolite of proanthocyanidins. We demonstrated that DHPV has stronger prevention effect on tumor necrosis factor (TNF)-α-stimulated adhesion of THP-1 human monocytic cells to human umbilical vein endothelial cells compared to its potential precursors such as procyanidin A1, A2, B1 and B2, (+)catechin, (-)epicatechin and its microbial metabolites such as 3-(3,4-dihydroxyphenyl)propionic acid and 2-(3,4-dihydroxyphenyl)acetic acid. Mechanism study showed that DHPV prevents THP-1 monocyte-endothelial cell adhesion by downregulating TNF-α-stimulated expressions of the two biomarkers of atherosclerosis such as vascular cell adhesion molecule-1 and monocyte chemotactic protein-1, activation of nuclear factor kappa B transcription and phosphorylation of I kappa-B kinase and IκBα. We suggested that DHPV has higher potentiality in prevention of atherosclerosis among the proanthocyanidin metabolites.


Assuntos
Adesão Celular/efeitos dos fármacos , Comunicação Celular/efeitos dos fármacos , Células Endoteliais/metabolismo , Monócitos/metabolismo , Proantocianidinas/farmacologia , Linhagem Celular , Células Endoteliais/imunologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Redes e Vias Metabólicas , Monócitos/imunologia , NF-kappa B/genética , NF-kappa B/metabolismo , Fosforilação , Proantocianidinas/metabolismo , Regiões Promotoras Genéticas , Substâncias Protetoras , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo
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