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Targeting MAPK/NF-κB Pathways in Anti-Inflammatory Potential of Rutaecarpine: Impact on Src/FAK-Mediated Macrophage Migration.
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- Additional Information
- Source:
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
- Publication Information:
Original Publication: Basel, Switzerland : MDPI, [2000-
- Subject Terms:
- Abstract:
Studies have discovered that different extracts of Evodia rutaecarpa and its phytochemicals show a variety of biological activities associated with inflammation. Although rutaecarpine, an alkaloid isolated from the unripe fruit of E. rutaecarpa , has been exposed to have anti-inflammatory properties, the mechanism of action has not been well studied. Thus, this study investigated the molecular mechanisms of rutaecarpine (RUT) in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. RUT reserved the production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF-α), and interleukin (IL)-1β in the LPS-induced macrophages. RUT showed an inhibitory effect on the mitogen-activated protein kinases (MAPKs), and it also inhibited nuclear transcription factor kappa-B (NF-κB) by hindering IκBα and NF-κB p65 phosphorylation and p65 nuclear translocation. The phospho-PI3K and Akt was concentration-dependently suppressed by RUT. However, RUT not only suggestively reduced the migratory ability of macrophages and their numbers induced by LPS but also inhibited the phospho-Src, and FAK. Taken together, these results indicate that RUT participates a vital role in the inhibition of LPS-induced inflammatory processes in RAW 264.7 macrophages and that the mechanisms involve PI3K/Akt and MAPK-mediated downregulation of NF-κB signaling pathways. Notably, reducing the migration and number of cells induced by LPS via inhibiting of Src/FAK pathway was also included to the anti-inflammatory mechanism of RUT. Therefore, RUT may have potential benefits as a therapeutic agent against chronic inflammatory diseases.
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- Grant Information:
MOST 107-2320-B-038-035-MY2 and MOST 108-2320-B-038-031-MY3 Ministry of Science and Technology of Taiwan; DP2-107-21121-N-02 Taipei Medical University, Taiwan; 108CM-TMU-04 Chi Mei Medical Center-Taipei Medical University, Taiwan; 2021SKHAND005 Shin Kong Wu Ho-Su Memorial Hospital , Taiwan
- Contributed Indexing:
Keywords: MAPK; NF-κB; PI3K/Akt; Src/FAK; anti-inflammation; cell migration; molecular mechanism; rutaecarpine
- Accession Number:
0 (Anti-Inflammatory Agents)
0 (Indole Alkaloids)
0 (Interleukin-1beta)
0 (Lipopolysaccharides)
0 (NF-kappa B)
0 (Quinazolines)
0 (Transcription Factor RelA)
0 (Tumor Necrosis Factor-alpha)
139874-52-5 (NF-KappaB Inhibitor alpha)
31C4KY9ESH (Nitric Oxide)
8XZV289PRY (rutecarpine)
EC 1.14.13.39 (Nitric Oxide Synthase Type II)
EC 1.14.99.1 (Cyclooxygenase 2)
EC 2.7.10.2 (Focal Adhesion Kinase 1)
EC 2.7.10.2 (Proto-Oncogene Proteins pp60(c-src))
EC 2.7.10.2 (Ptk2 protein, mouse)
EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
- Publication Date:
Date Created: 20220111 Date Completed: 20220131 Latest Revision: 20220131
- Publication Date:
20221213
- Accession Number:
PMC8745017
- Accession Number:
10.3390/ijms23010092
- Accession Number:
35008520
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