The Anti-Inflammatory Effects and Mechanisms of Eupafolin in Lipopolysaccharide-Induced Inflammatory Responses in RAW264.7 Macrophages.

Chin-Chaun Chen,Ming-Wei Lin,Chan-Jung Liang,Shu-Huei Wang,Partha Mukhopadhyay

doi:10.1371/journal.pone.0158662

Abstract

Eupafolin is a flavone isolated from Artemisia princeps Pampanini (family Asteraceae). The aim of this study was to examine the anti-inflammatory effects of eupafolin in lipopolysaccharide (LPS)-treated RAW264.7 macrophages and LPS-induced mouse skin and lung inflammation models and to identify the mechanism underlying these effects. Eupafolin decreased the LPS-induced release of inflammatory mediators (iNOS, COX-2 and NO) and proinflammatory cytokines (IL-6 and TNF-α) from the RAW264.7 macrophages. Eupafolin inhibited the LPS-induced phosphorylation of p38 MAPK, ERK1/2, JNK, AKT and p65 and the nuclear translocation of p65 and c-fos. These effects were mainly mediated by the inhibition of JNK. In the mouse paw and lung models, eupafolin effectively suppressed the LPS-induced edema formation and down-regulated iNOS and COX-2 expression. These results demonstrated that eupafolin exhibits anti-inflammatory properties and suggested that eupafolin can be developed as an anti-inflammatory agent.

Highlights

Inflammation is a physiological response against harmful stimuli, such as pathogens, in the body
The results showed that 0–80 μM eupafolin was not cytotoxic to the RAW264.7 macrophages
To determine whether eupafolin had an anti-inflammatory effect, we examined the expression of COX-2 and iNOS in the LPSinduced RAW264.7 macrophages

Summary

Introduction

Inflammation is a physiological response against harmful stimuli, such as pathogens, in the body. By inducing the release of signaling molecules, inflammation exerts protective effects that neutralize injurious pathogens. Macrophages are important cells of the immune system that act as the first line of defense against invading agents (bacteria, viruses, and fungi) and respond to pathogen attacks by releasing cellular signaling molecules and various proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin 1-β (IL-1β) and IL-6, and inflammatory mediators, such as nitric oxide (NO), prostaglandin E2 (PGE2), and cyclooxygenase-2 (COX-2)[1,2,3]. Chronic inflammation and deregulated cytokine production are associated with conditions such as cancer progression, cardiovascular disease, PLOS ONE | DOI:10.1371/journal.pone.0158662. One effective strategy for developing therapeutic agents to treat severe inflammation is the identification of agents that regulate the production of proinflammatory mediators

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