Immunomodulation effects of isochlorogenic acid a from apple on RAW264.7 cells via modulation of TLR2 and TLR4 target proteins.

The incorporation of nutrients with immunomodulatory properties into the daily diet has emerged as a pressing health requirement. The aim of this study was to screen apple polyphenols with immunomodulatory activitiy using molecular docking and to investigate the modulatory effects of apple polyphenol-isochlorogenic acid A on the activation of macrophage immune responses and the inhibition of inflammation through the immunoreceptors TLR2 and TLR4. The results showed that isochlorogenic acid A of apple polyphenols had high docking scores with TLR2 and TLR4. The isochlorogenic acid A exhibited favorable ADMET properties and water solubility. Cellular assays results showed that isochlorogenic acid A enhanced the viability of RAW264.7 cells and promoted the expression of NO, TNF-α, IL-1β, TLR2, and TLR4 in cells, and inhibited the expression of NO, TNF-α, IL-6, TLR2, and TLR4 in inflammatory cells. The isochlorogenic acid A bound to residues Phe325, Phe349, Leu350 and Pro352 of TLR2 by hydrogen bonding and hydrophobic interactions, and to residues Val82, Arg90, Ser127, Cys133 and Ser441 of TLR4-MD-2 via π-alkyl and hydrogen bonds. In summary, the immunoreceptors TLR2 and TLR4 play a crucial role as recognition receptors for isochlorogenic acid A of apple polyphenols in the regulation of cellular immune response and inflammation. [Display omitted] • Isochlorogenic acid A from apple had immunomodulatory activity. • Isochlorogenic acid A had high binding affinity to TLR2 and TLR4. • Isochlorogenic acid A bound to TLR2/4 via hydrogen bonding and hydrophobic interactions. • Isochlorogenic acid A could bidirectionally regulate the expression of NO and cytokines. [ABSTRACT FROM AUTHOR]