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

A polyphenol‐enriched fraction (PEF) from Acalypha wilkesiana , 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 E 2 (PGE 2 ) 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‐ α (TNF‐ α ), interleukin‐ (IL‐) 1 β , 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‐ κ B (NF‐κB) by preventing the degradation of inhibitor κB‐ α (IκB‐ α ). 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‐ κ 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‐ κ B signaling pathway, suggesting the therapeutic potential of PEF for inflammatory diseases.