5-(3',4'-Dihydroxyphenyl-γ-valerolactone), a Major Microbial Metabolite of Proanthocyanidin, Attenuates THP-1 Monocyte-Endothelial Adhesion

• Published in: International journal of molecular sciences Vol. 18; no. 7; p. 1363
• Main Authors: Lee, Charles C, Kim, Jong Hun, Kim, Ji Seung, Oh, Yun Sil, Han, Seung Min, Park, Jung Han Yoon, Lee, Ki Won, Lee, Chang Yong
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 26-06-2017; MDPI AG
• Subjects: 5-(3′,4′-dihydroxyphenyl-γ-valerolactone); atherosclerosis prevention; Cell Adhesion - drug effects; Cell Communication - drug effects; Cell Line; Endothelial Cells - immunology; Endothelial Cells - metabolism; Gene Expression Regulation - drug effects; Humans; Metabolic Networks and Pathways; monocyte-endothelial adhesion; Monocytes - immunology; Monocytes - metabolism; NF-kappa B - genetics; NF-kappa B - metabolism; Phosphorylation; proanthocyanidin microbial metabolite; Proanthocyanidins - metabolism; Proanthocyanidins - pharmacology; Promoter Regions, Genetic; Protective Agents; Signal Transduction - drug effects; Tumor Necrosis Factor-alpha - pharmacology; Vascular Cell Adhesion Molecule-1 - genetics; Vascular Cell Adhesion Molecule-1 - metabolism; 5-(3′,4′-dihydroxyphenyl-γ-valerolactone); monocyte-endothelial adhesion; atherosclerosis prevention; proanthocyanidin microbial metabolite
• ISSN: 1422-0067; 1422-0067
• DOI: 10.3390/ijms18071363

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.