Phenolic Acid–Amino Acid Adducts Exert Distinct Immunomodulatory Effects in Macrophages Compared to Parent Phenolic Acids

Abstract

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.

Effects of Dietary Supplemental Chlorogenic Acid and Baicalin on the Growth Performance and Immunity of Broilers Challenged with Lipopolysaccharide

“…A study suggested that chlorogenic acid and baicalin are the biologically active ingredients in honeysuckle and scutellaria, respectively. Some in vitro studies demonstrated that chlorogenic acid helped alleviate the LPS-induced inflammatory response in macrophages [ 7 , 8 ]. Chlorogenic acid reduced the damage to vascular endothelial cells caused by acute increases in the Nitric oxide(NO) levels in intestinal mucosal microvascular endothelial cells that were challenged with LPS [ 9 ].…”

Anti-Inflammatory Effect of Chamaecyparis obtusa (Siebold & Zucc.) Endl. Leaf Essential Oil

“…Given the demonstrated expression of pro-inflammatory IL-1β , IL-6 , and TNF-α in LPS-induced RAW 264.7 cells at the mRNA level and the results of our analysis of downstream signaling molecules, a cytokine array was performed. Based on the GSE206519 database set [ 24 ], 26 cytokines were upregulated, and 7 cytokines were downregulated in LPS-induced RAW 264.7 cells ( Figure 6 a–c and Figure S1 ). Both COD and sabinene downregulated five cytokines: IL-1β, IL-6, IL-27, granulocyte–macrophage colony-stimulating factor (GM-CSF), and IL-1 receptor antagonist (IL-1ra) ( Figure 6 d).…”

Tea Consumption and New-Onset Acute Kidney Injury: The Effects of Milk or Sweeteners Addition and Caffeine/Coffee

“…It's biologically plausible. Recent studies have found that protein-polyphenol interactions may enhance the antiinflammatory activity of phenolic compounds [35,36]. Additionally, milk proteins may possess renal-protective functions, such as suppressing the angiotensin converting enzyme and lowering blood pressure, through peptides (casokinins and lactokinins) that have vasoactive properties [37][38][39].…”