Journal Article

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

Huang, Lisen, Wang, Gueyhorng, Zhang, Gang, Liu, Huaxin, Pang, Haiyue, Wu, Hongtan, Sun, Cuiling, Zheng, Yongbiao, Chen, Yupei

2018

Overview

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 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-α (TNF-α), interleukin- (IL-) 1β, 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-κB (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-κB 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-κB signaling pathway, suggesting the therapeutic potential of PEF for inflammatory diseases.

• Publisher: Hindawi Publishing Corporation,Hindawi,John Wiley & Sons, Inc
• Subject: Acalypha - chemistry / Acetaminophen / Acetaminophen - adverse effects / Analgesics / Analysis / Animals / Anti-Inflammatory Agents - pharmacology / Anti-Inflammatory Agents - therapeutic use / Anti-inflammatory drugs / Arthritis / Chemical and Drug Induced Liver Injury - complications / Cytokines / Drug therapy / Gene expression / Inflammation / Inflammatory diseases / Interleukins / Kinases / Lipopolysaccharides - metabolism / Liver / Macrophages / Macrophages - metabolism / Metabolites / Mice / Mitochondrial DNA / Mitogens / Natural products / Neutrophils / Nitric oxide / Oxidative stress / Pathogenesis / Pattern recognition / Plant Extracts - chemistry / Polyphenols / Prostaglandins E / Protein kinases / Rodents / Toxicology / Tumor necrosis factor