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Int. J. Mol. Sci. 2017, 18(7), 1363; doi:10.3390/ijms18071363

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

1
Department of Food Science, Cornell University, Ithaca, NY 14853, USA
2
Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea
3
Major in Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Korea
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 27 April 2017 / Revised: 7 June 2017 / Accepted: 22 June 2017 / Published: 26 June 2017
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Abstract

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. View Full-Text
Keywords: 5-(3′,4′-dihydroxyphenyl-γ-valerolactone); proanthocyanidin microbial metabolite; atherosclerosis prevention; monocyte-endothelial adhesion 5-(3′,4′-dihydroxyphenyl-γ-valerolactone); proanthocyanidin microbial metabolite; atherosclerosis prevention; monocyte-endothelial adhesion
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Lee, C.C.; Kim, J.H.; Kim, J.S.; Oh, Y.S.; Han, S.M.; Park, J.H.Y.; Lee, K.W.; Lee, C.Y. 5-(3′,4′-Dihydroxyphenyl-γ-valerolactone), a Major Microbial Metabolite of Proanthocyanidin, Attenuates THP-1 Monocyte-Endothelial Adhesion. Int. J. Mol. Sci. 2017, 18, 1363.

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