PMID- 33297427 OWN - NLM STAT- MEDLINE DCOM- 20210419 LR - 20210419 IS - 1420-3049 (Electronic) IS - 1420-3049 (Linking) VI - 25 IP - 23 DP - 2020 Dec 7 TI - Euodia pasteuriana Methanol Extract Exerts Anti-Inflammatory Effects by Targeting TAK1 in the AP-1 Signaling Pathway. LID - 10.3390/molecules25235760 [doi] LID - 5760 AB - 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-alpha (TNF-alpha), 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. FAU - Zhang, Jianmei AU - Zhang J AUID- ORCID: 0000-0003-0817-4809 AD - Department of Integrative Biotechnology, and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea. FAU - Kim, Mi-Yeon AU - Kim MY AD - School of Systems Biomedical Science, Soongsil University, Seoul 06978, Korea. FAU - Cho, Jae Youl AU - Cho JY AUID- ORCID: 0000-0001-8141-9927 AD - Department of Integrative Biotechnology, and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea. LA - eng GR - 2017R1A6A1A03015642/National Research Foundation of Korea/ GR - 2016R1D1A1B01011371/National Research Foundation of Korea/ PT - Journal Article DEP - 20201207 PL - Switzerland TA - Molecules JT - Molecules (Basel, Switzerland) JID - 100964009 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Plant Extracts) RN - 0 (Solvents) RN - 0 (Transcription Factor AP-1) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 2.7.11.25 (MAP Kinase Kinase Kinases) RN - EC 2.7.11.25 (MAP kinase kinase kinase 7) RN - Y4S76JWI15 (Methanol) SB - IM MH - Animals MH - Anti-Inflammatory Agents/*chemistry/*pharmacology MH - Evodia/*chemistry MH - HEK293 Cells MH - Humans MH - MAP Kinase Kinase Kinases/*metabolism MH - Methanol/chemistry MH - Mice MH - Nitric Oxide/metabolism MH - Plant Extracts/*chemistry/*pharmacology MH - RAW 264.7 Cells MH - Signal Transduction/*drug effects MH - Solvents/chemistry MH - Transcription Factor AP-1/*metabolism PMC - PMC7730574 OTO - NOTNLM OT - AP-1 OT - Euodia pasteuriana OT - TAK1 OT - anti-inflammatory COIS- The authors declare no conflict of interest. EDAT- 2020/12/11 06:00 MHDA- 2021/04/20 06:00 PMCR- 2020/12/07 CRDT- 2020/12/10 01:03 PHST- 2020/11/06 00:00 [received] PHST- 2020/11/29 00:00 [revised] PHST- 2020/12/05 00:00 [accepted] PHST- 2020/12/10 01:03 [entrez] PHST- 2020/12/11 06:00 [pubmed] PHST- 2021/04/20 06:00 [medline] PHST- 2020/12/07 00:00 [pmc-release] AID - molecules25235760 [pii] AID - molecules-25-05760 [pii] AID - 10.3390/molecules25235760 [doi] PST - epublish SO - Molecules. 2020 Dec 7;25(23):5760. doi: 10.3390/molecules25235760.