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

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.

Immune-Enhancing Effects of a Novel Glucan from Purple Sweet Potato Ipomoea batatas (L.) Lam on RAW264.7 Macrophage Cells via TLR2- and TLR4-Mediated Pathways

“…The activator protein-1 (AP-1) as another major transcription factor is involved in the immune response except NF-κB signaling, and c-Jun and c-Fos were the major AP-1 proteins, which can control the expression of cytokines and promote immune responses. , So we checked the expressions of c-Jun and c-Fos and found that they were increased by PSPP-1 treatment, which were significantly different in comparison to the control group ( P < 0.05) (Figure ). The TLR4/AP-1 signaling pathway is very important in macrophage activation-mediated immunity, and the active upstream factors of AP-1 such as IRAK1, TAK1, and MAPKs were regulated synchronously by PSPP-1.…”

Anti-Gastritis and Anti-Lung Injury Effects of Pine Tree Ethanol Extract Targeting Both NF-κB and AP-1 Pathways

“…The inhibition of NO production by Pd-EE was observed at the transcriptional level, since iNOS expression was attenuated ( Figure 1 ). In fact, the activity of inflammation-regulatory transcription factors NF-κB and AP-1 was strongly downregulated ( Figure 2 ), implying that these transcription factors could be targeted by Pd-EE, as shown in the cases of other medicinal plants such as Olea europaea , Phyllanthus acidus , Euodia pasteuriana , Panax ginseng , and Alisma canaliculatum [ 36 , 37 , 38 , 39 ].…”

p38-dependent c-Jun degradation contributes to reduced PGE2 production in sodium orthovanadate-treated macrophages

“…In order to obtain a better understanding of the regulation of COX-2 expression by SO, we observed the level of c-Jun, as this transcription factor is a major subunit of AP-1, which plays a critical role in controlling COX-2 expression in RAW264.7 cells under LPS-stimulated conditions ( 10 ). An increased level of c-Jun was observed 45, 60, and 75 minutes after LPS treatment, while pre-treatment with SO showed a decrease in c-Jun levels, as caused by nuclear fractionation, immunofluorescence, and reporter gene assay ( Fig.…”