Abstract
Euodia pasteuriana A. Chev. ex Guillaumin, also known as Melicope accedens (Blume) T.G. Hartley, is a herbal medicinal plant native to Vietnam. Although Euodia pasteuriana 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 Euodia pasteuriana 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.
Highlights
Inflammation is a fast, complex biological response in mammals that aids in the elimination of harmful stimuli and the repair of damaged tissue [1]
The pathogen-associated molecular pattern (PAMP) is a complex formed through pathogen recognition receptors (PRRs) in cells and the conserved structure of pathogens, which can be recognized by the related receptor and induce
The aim of this research was to demonstrate the anti-inflammatory effects of Euodia pasteuriana and its molecular mechanisms in the activator protein 1 (AP-1) signaling pathway
Summary
Inflammation is a fast, complex biological response in mammals that aids in the elimination of harmful stimuli and the repair of damaged tissue [1]. Immune cells, such as neutrophils, monocytes, and macrophages, can be quickly recruited to sites of injury and inflammation, where they identify foreign invaders and release chemokines, cytokines, and eicosanoids to regulate immunity and restore the body’s physiological balance [2,3]. The pathogen-associated molecular pattern (PAMP) is a complex formed through pathogen recognition receptors (PRRs) in cells and the conserved structure of pathogens, which can be recognized by the related receptor and induce.
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