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Current Nutraceuticals

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ISSN (Print): 2665-9786
ISSN (Online): 2665-9794

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Research Article

Efficient Transport and Biotransformation of Dipeptide-like Tyrosine/ Phenylalanine-Conjugated Phenolic Amide Esters in THP-1 Cells and PBMCs: A Potential Means for Transporting Compounds Inside Monocytes/Macrophages

Author(s): Jae B. Park

Volume 3, Issue 2, 2022

Published on: 15 February, 2022

Article ID: e241221199425 Pages: 12

DOI: 10.2174/2665978603666211224121836

Price: $65

Abstract

Background: Recent studies suggest that dipeptide-like tyrosine/phenylalanine-conjugated phenolic amide compounds may contain several biological activities, including anti-inflammatory activity. However, there is currently no information about their transport and biotransformation in monocytes/macrophages involved in inflammation process.

Objective: The objective of this study was to investigate cell transport and biotransformation of the phenolic amides and esters in monocyte/macrophage-like cells.

Methods: Cell transport and biotransformation of the phenolic amides and esters (N-coumaroylphenylalanine, N-caffeoylphenylalanine, N-feruloylphenylalanine, N-coumaroyltyrosine, Ncaffeoyltyrosine, N-feruloyltyrosine, and their O-methyl esters) were investigated in THP-1 cells and PBMCs using HPLC, cellular, and kinetics methods.

Results: In THP-1 cells, the phenolic amides were not transported significantly, but their O-methyl esters were transported significantly (P < 0.02). Also, the transport of the esters was found to be sodium-independent and pH-dependent. Among the tested esters, N-feruloylphenylalanine-Omethyl ester showed the highest uptake (Km of 25 μM), and the uptake was inhibited by PepT1/2 substrate and blocker (GlySar and enalapril) in THP-1 cells. Particularly, enalapril competitively inhibited the uptake with Ki of 560 μM. The data also showed that N-feruloylphenylalanine-Omethyl ester and N-feruloyltyrosine-O-methyl ester could be biotransformed into parent phenolic amides in THP-1 cells. Similarly, these ester compounds were also found to be transported and biotransformed in PBMCs.

Conclusion: The data suggest that dipeptide-like tyrosine/phenylalanine-conjugated phenolic amide esters may be transported and biotransformed in THP-1 cells and PBMCs.

Keywords: Dipeptide-like tyrosine, phenylalanine-conjugated phenolic amide esters, bioactives, nutraceuticals, transport, biotransformation, PepT2, THP-1 cells, PBMCs.

Graphical Abstract

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