Thumbnail
Access Restriction
Open

Author Tsai, Ming-Horng ♦ Lin, Zih-Chan ♦ Liang, Chan-Jung ♦ Yen, Feng-Lin ♦ Chiang, Yao-Chang ♦ Lee, Chiang-Wen ♦ Diseases, Chronic
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ ANTIBODIES ♦ ANTIOXIDANTS ♦ DNA ♦ FIBROBLASTS ♦ GENE REGULATION ♦ IN VIVO ♦ INFLAMMATION ♦ INHIBITION ♦ METHANOL ♦ MICE ♦ OXIDASES ♦ PHOSPHORYLATION ♦ PHOSPHOTRANSFERASES ♦ PROMOTERS ♦ PROSTAGLANDINS ♦ RECEPTORS ♦ SKIN DISEASES ♦ TRANSCRIPTION FACTORS
Abstract Eupafolin, a major active component found in the methanol extracts of Phyla nodiflora, has been used to treat inflammation of skin. We examined its effects on cyclooxygenase-2 (COX-2) expression in LPS-treated human dermal fibroblasts. Lipopolysaccharide (LPS) significantly increased prostaglandin-E2 (PGE2) production associated with increased COX-2 expression in Hs68 cells. This effect was blocked by eupafolin, TLR-4 antibody, antioxidants (APO and NAC), as well as inhibitors, including U0126 (ERK1/2), SB202190 (p38), SP600125 (JNK1/2), and Tanshinone IIA (AP-1). In gene regulation level, qPCR and promoter assays revealed that COX-2 expression was attenuated by eupafolin. In addition, eupafolin also ameliorated LPS-induced p47 phox activation and decreased reactive oxygen species (ROS) generation and NADPH oxidase (Nox) activity. Moreover, pretreatment with eupafolin and APO led to reduced LPS-induced phosphorylation of ERK1/2, JNK, and p38. Further, eupafolin attenuated LPS-induced increase in AP-1 transcription factor binding activity as well as the increase in the phosphorylation of c-Jun and c-Fos. In vivo studies have shown that in dermal fibroblasts of LPS treated mice, eupafolin exerted anti-inflammation effects by decreasing COX-2 protein levels. Our results reveal a novel mechanism for anti-inflammatory and anti-oxidative effects of eupafolin that involved inhibition of LPS-induced ROS generation, suppression of MAPK phosphorylation, diminished DNA binding activity of AP-1 and attenuated COX-2 expression leading to reduced production of prostaglandin E2 (PGE2). Our results demonstrate that eupafolin may be used to treat inflammatory responses associated with dermatologic diseases. - Highlights: • LPS activates the Nox2/p47{sup phox}/JNK/AP-1 and induces COX2 expression in Hs68 cells. • Eupafolin inhibits LPS-induced COX-2 expression via Nox2/p47{sup phox} inhibition. • Eupafolin may be used in the treatment of skin diseases involving inflammation.
ISSN 0041008X
Educational Use Research
Learning Resource Type Article
Publisher Date 2014-09-01
Publisher Place United States
Journal Toxicology and Applied Pharmacology
Volume Number 279
Issue Number 2


Open content in new tab

   Open content in new tab