Phenolic Acid-Amino Acid Adducts Exert Distinct Immunomodulatory Effects in Macrophages Compared to Parent Phenolic Acids
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Phenolic Acid-Amino Acid Adducts Exert Distinct Immunomodulatory Effects in Macrophages Compared to Parent Phenolic Acids. / Liu, Jingyuan; Poojary, Mahesha M.; Zhu, Ling; Williams, Andrew R.; Lund, Marianne N.
In: Journal of Agricultural and Food Chemistry, Vol. 71, No. 5, 2023, p. 2344−2355.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Phenolic Acid-Amino Acid Adducts Exert Distinct Immunomodulatory Effects in Macrophages Compared to Parent Phenolic Acids
AU - Liu, Jingyuan
AU - Poojary, Mahesha M.
AU - Zhu, Ling
AU - Williams, Andrew R.
AU - Lund, Marianne N.
PY - 2023
Y1 - 2023
N2 - Caffeic acid (CA) and chlorogenic acid (CGA) are commonly found phenolic acids in plant-derived foods and beverages. Their corresponding adducts with cysteine (Cys) have been detected in coffee-containing beverages. However, despite the well-documented antioxidant and anti-inflammatory activity of CA and CGA, the immunomodulatory activities of the Cys adducts (CA-Cys and CGA-Cys) are unknown. The adducts were therefore synthesized, and their immunomodulatory effects were studied in lipopolysaccharide (LPS)-treated RAW 264.7 cells and compared to the activity of the parent phenolic acids. CA and CGA generally down-regulated the inflammatory responses. However, RNA-sequencing showed that the LPS-induced pathways related to Toll-like receptor signaling, chemokine signaling, and NOD-like receptor signaling, and JAK-STAT/MAPK signaling pathways were upregulated in adduct-treated cells relative to parent phenolic acids, while neurodegenerative disorder-related pathways and metabolic pathways were downregulated. Production of prostaglandin E2 (PGE2), interleukin-6, tumor necrosis factor-α (TNF-α), and reactive oxygen species (ROS) was all inhibited by CA and CGA (P < 0.05). PGE2 and TNF-α were further suppressed in adduct-stimulated cells (P < 0.05), but ROS production was increased. For example, TNF-α produced by 100 μM CGA-stimulated cells and 100 μM CGA-Cys adduct-stimulated cells were 4.46 ± 0.23 and 1.61 ± 0.18 ng/mL, respectively. Thus, the addition of the Cys moiety drastically alters the anti-inflammatory activity of phenolic compounds.
AB - Caffeic acid (CA) and chlorogenic acid (CGA) are commonly found phenolic acids in plant-derived foods and beverages. Their corresponding adducts with cysteine (Cys) have been detected in coffee-containing beverages. However, despite the well-documented antioxidant and anti-inflammatory activity of CA and CGA, the immunomodulatory activities of the Cys adducts (CA-Cys and CGA-Cys) are unknown. The adducts were therefore synthesized, and their immunomodulatory effects were studied in lipopolysaccharide (LPS)-treated RAW 264.7 cells and compared to the activity of the parent phenolic acids. CA and CGA generally down-regulated the inflammatory responses. However, RNA-sequencing showed that the LPS-induced pathways related to Toll-like receptor signaling, chemokine signaling, and NOD-like receptor signaling, and JAK-STAT/MAPK signaling pathways were upregulated in adduct-treated cells relative to parent phenolic acids, while neurodegenerative disorder-related pathways and metabolic pathways were downregulated. Production of prostaglandin E2 (PGE2), interleukin-6, tumor necrosis factor-α (TNF-α), and reactive oxygen species (ROS) was all inhibited by CA and CGA (P < 0.05). PGE2 and TNF-α were further suppressed in adduct-stimulated cells (P < 0.05), but ROS production was increased. For example, TNF-α produced by 100 μM CGA-stimulated cells and 100 μM CGA-Cys adduct-stimulated cells were 4.46 ± 0.23 and 1.61 ± 0.18 ng/mL, respectively. Thus, the addition of the Cys moiety drastically alters the anti-inflammatory activity of phenolic compounds.
U2 - 10.1021/acs.jafc.2c06658
DO - 10.1021/acs.jafc.2c06658
M3 - Journal article
C2 - 36715127
VL - 71
SP - 2344−2355
JO - Journal of Agricultural and Food Chemistry
JF - Journal of Agricultural and Food Chemistry
SN - 0021-8561
IS - 5
ER -
ID: 334258833