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.

Outcomes of Gallic Acid on Alternariol Induced Cyto-Morphic and Genotoxic In Vivo Changes in Parotid Gland: 4-HNE Incorporated

“…The observable amelioration of AOH-induced inflammatory cellular infiltrations in GA group suggests its anti-inflammatory properties. These results were in line with Ahn et al [56] who proved that GA suppressed prostaglandin E 2 (PGE 2 ), TNF-α, IL-1β and NF-κB expression in RAW264.7 macrophages.…”

Evaluation of anti-inflammatory activity of compounds isolated from the rhizome of Ophiopogon japonicas

“…Moreover, we firstly investigated the effect and mechanism of 4'- O -Demethylophiopogonanone E on LPS-stimulated NO and pro-inflammatory cytokines including IL-1β and IL-6. NO is synthesized from L -arginine by iNOS, and its overproduction is involved in cytotoxicity and tissue damage in the inflammatory process [34, 35]. Overexpression of iNOS by inflammatory agents accompanied with inflammatory disorder including IL-1β and IL-6, which are resulted in acute and chronic response to inflammatory diseases [36].…”

Astragalus polysaccharides exerts immunomodulatory effects via TLR4-mediated MyD88-dependent signaling pathway in vitro and in vivo

“…It is confusing that the mRNA and protein expressions of AP-1 were increased by APS and LPS in both MyD88 +/+ mice and MyD88 −/− mice. AP-1, which is another eukaryotic transcription factor targeted by MAPK signaling pathways49, is an important regulatory protein involved in various biological activities, and also contributes to inflammatory and immune responses50. Thus, we assumed that, when MyD88 was deficient, APS activated AP-1 through another signaling pathway other than the TLR4-MyD88-denpendent signaling pathway.…”