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

  • Int J Mol Sci. 2017 Jun 26;18(7):1363. doi: 10.3390/ijms18071363.
Charles C Lee  1 Jong Hun Kim  2 Ji Seung Kim  3 Yun Sil Oh  4 Seung Min Han  5 Jung Han Yoon Park  6 Ki Won Lee  7  8 Chang Yong Lee  9
Affiliations
  • 1. Department of Food Science, Cornell University, Ithaca, NY 14853, USA. [email protected].
  • 2. Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea. [email protected].
  • 3. Major in Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Korea. [email protected].
  • 4. Major in Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Korea. [email protected].
  • 5. Major in Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Korea. [email protected].
  • 6. Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea. [email protected].
  • 7. Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea. [email protected].
  • 8. Major in Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Korea. [email protected].
  • 9. Department of Food Science, Cornell University, Ithaca, NY 14853, USA. [email protected].
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.

Keywords
5-(3′,4′-dihydroxyphenyl-γ-valerolactone); atherosclerosis prevention; monocyte-endothelial adhesion; proanthocyanidin microbial metabolite.
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