Anti‐Inflammatory Effect of a Polyphenol‐Enriched Fraction from <i>Acalypha wilkesiana</i> on Lipopolysaccharide‐Stimulated RAW 264.7 Macrophages and Acetaminophen‐Induced Liver Injury in Mice

Abstract

A polyphenol-enriched fraction (PEF) from <i>Acalypha wilkesiana</i>, whose leaves have been traditionally utilized for the treatment of diverse medical ailments, was investigated for the anti-inflammatory effect and molecular mechanisms by using lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophages and acetaminophen- (APAP-) induced liver injury mouse model. Results showed that PEF significantly attenuated LPS-induced nitric oxide (NO) and prostaglandin E₂ (PGE₂) production and suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) in RAW 264.7 macrophages. PEF also reduced the secretion of proinflammatory cytokines including tumor necrosis factor-<i>α</i> (TNF-<i>α</i>), interleukin- (IL-) 1<i>β</i>, and IL-6 in LPS-stimulated RAW 264.7 macrophages. Moreover, PEF potently inhibited LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs) as well as the activation of nuclear factor-<i>κ</i>B (NF-κB) by preventing the degradation of inhibitor κB-<i>α</i> (IκB-<i>α</i>). In vivo, PEF pretreatment ameliorated APAP-induced liver injury and hepatic inflammation, as presented by decreased hepatic damage indicators and proinflammatory factors at both plasma and gene levels. Additionally, PEF pretreatment remarkably diminished Toll-like receptor 3 (TLR3) and TLR4 expression and the subsequent MAPKs and NF-<i>κ</i>B activation. HPLC analysis revealed that two predominantly polyphenolic compounds present in PEF were geraniin and corilagin. These results indicated that PEF has an anti-inflammatory effect, and its molecular mechanisms may be involved in the inactivation of the TLR/MAPK/NF-<i>κ</i>B signaling pathway, suggesting the therapeutic potential of PEF for inflammatory diseases.