Euodia pasteuriana Methanol Extract Exerts Anti-Inflammatory Effects by Targeting TAK1 in the AP-1 Signaling Pathway

• Published in: Molecules (Basel, Switzerland) Switzerland), 2020-12, Vol.25 (23), p.5760
• Main Authors: Zhang, Jianmei, Kim, Mi-Yeon, Cho, Jae Youl
• Format: Article
• Language: English
• Subjects: Activator protein 1; Animals; anti-inflammatory; Anti-inflammatory agents; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; AP-1; Arthritis; c-Jun protein; Chemokines; Cytokines; Cytotoxicity; Euodia pasteuriana; Evodia - chemistry; Gelatinase A; Gelatinase B; Gene expression; Growth factors; HEK293 Cells; Herbal medicine; Humans; Immunoblotting; Inflammation; Inflammatory diseases; Interleukin 6; Kinases; Ligands; Lipopolysaccharides; Macrophages; MAP Kinase Kinase Kinases - metabolism; Matrix metalloproteinase; Matrix metalloproteinases; Medicinal plants; Metalloproteinase; Methanol - chemistry; Mice; Nitric oxide; Nitric Oxide - metabolism; Pathogens; Phosphorylation; Plant Extracts - chemistry; Plant Extracts - pharmacology; Polyinosinic:polycytidylic acid; Polymerase chain reaction; Proteins; RAW 264.7 Cells; Reverse transcription; Signal transduction; Signal Transduction - drug effects; Solvents - chemistry; Stromelysin 1; TAK1; TAK1 protein; Transcription Factor AP-1 - metabolism; Transcription factors; Translocation; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25235760

A. Chev. ex Guillaumin, also known as (Blume) T.G. Hartley, is a herbal medicinal plant native to Vietnam. Although is used as a traditional medicine to treat a variety of inflammatory diseases, the pharmacological mechanisms related to this plant are unclear. This study aimed to investigate the anti-inflammatory effects of a methanol extract of leaves (Ep-ME) on the production of inflammatory mediators, the mRNA expression of proinflammatory genes, and inflammatory signaling activities in macrophage cell lines. The results showed that Ep-ME strongly suppressed the release of nitric oxide (NO) in RAW264.7 cells induced with lipopolysaccharide (LPS), pam3CysSerLys4 (Pam3CSK), and polyinosinic-polycytidylic acid (poly I:C) without cytotoxicity. A reverse transcription-polymerase chain reaction further confirmed that Ep-ME suppressed the expression of interleukin 6 (IL-6), matrix metalloproteinase-1 (MMP1), matrix metalloproteinase-2 (MMP2), matrix metalloproteinase-3 (MMP3), tumor necrosis factor-α (TNF-α), and matrix metalloproteinase-9 (MMP9) at the transcriptional level and reduced the luciferase activities of activator protein 1 (AP-1) reporter promoters. In addition, immunoblotting analyses of the whole lysate and nuclear fraction, as well as overexpression assays demonstrated that Ep-ME decreased the translocation of c-Jun and suppressed the activation of transforming growth factor beta-activated kinase 1 (TAK1) in the AP-1 signaling pathways. These results imply that Ep-ME could be developed as an anti-inflammatory agent that targets TAK1 in the AP-1 signaling pathway.