Gallic Acid-g-Chitosan Modulates Inflammatory Responses in LPS-Stimulated RAW264.7 Cells Via NF-κB, AP-1, and MAPK Pathways.

Abstract

Chitosan is a naturally occurring polysaccharide, which has exhibited antioxidant, antimicrobial, and anti-cancer activities among others. Modification of chitosan by grafting phenolic compounds is a good strategy for improvement of bioactivities of chitosan. We investigated the anti-inflammatory action of gallic acid-grafted-chitosan (GAC) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. GAC inhibited the production of nitric oxide (NO) and prostaglandin E2 (PGE2) by inhibiting inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in LPS-stimulated RAW264.7 macrophages. GAC also suppressed the production and mRNA expression of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). GAC inactivated nuclear factor-κB (NF-κB) via inhibiting the phosphorylation and degradation of the NF-κB inhibitor, IκB. In addition, GAC suppresses the activation of activator protein-1 (AP-1) through the phosphorylation of mitogen-activated protein kinase (MAPK) such as extracellular signal-regulated kinase (ERK1/2), p38 MAPK, and c-Jun N-terminal kinase/stress-activated protein kinase (JNK). These results suggest that GAC has the potential anti-inflammatory action by downregulating transcriptional factors (NF-κB and AP-1) through MAPK signaling pathways.