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

Abstract

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.

Atraric Acid Exhibits Anti-Inflammatory Effect in Lipopolysaccharide-Stimulated RAW264.7 Cells and Mouse Models

“…The NFκB is then phosphorylated and converted to its active form. In the NFκB signaling pathway, MAPK regulates the activation of NFκB; the phosphorylation of MAPK induces the activation of NFκB followed by subsequent expression of inflammatory mediators and pro-inflammatory cytokines [ 10 , 22 ]. To investigate the effect of atraric acid on the MAPK/NFκB signaling pathway, LPS-stimulated RAW264.7 cells were treated with atraric acid to analyze the expression of the inflammatory mediators by Western blot.…”

“…There is a great interest in the discovery of biologically active natural products due to their activities with relatively low toxicity as compared to other modalities such as synthetic chemicals [ 10 ]. Numerous studies have shown that natural products are developed as beneficial dietary supplements for health and therapeutic agents against disease [ 25 ].…”

“…Tissues were fixed in 4% formalin and embedded in paraffin. Sections of 4 μm thickness were obtained and stained with H&E and histological changes were monitored under the microscope at × 400 magnification [ 10 , 30 ].…”

“…This leads to impaired cardiovascular function, pulmonary dysfunction, acute renal impairment, septic shock and, finally, death. Many studies have demonstrated that the inhibition of NFκB and MAPK activation is an important strategy for the treatment of inflammatory diseases [ 8 , 9 , 10 , 11 ].…”

Anti-Inflammatory and Antioxidant Effects of Carpesium cernuum L. Methanolic Extract in LPS-Stimulated RAW 264.7 Macrophages

“…S1 B). Redundant NO and PGE 2 , as inflammatory mediators, have been regarded as the main causes for acute inflammatory responses as well as chronic inflammatory diseases, such as osteoarthritis, rheumatoid arthritis, and inflammatory bowel disease [ 20 ]. In order to examine the effect of CLME on level of inflammatory mediators, we investigated NO and PGE 2 production in LPS-stimulated RAW 264.7 cells.…”