Targeting MAPK/NF-κB Pathways in Anti-Inflammatory Potential of Rutaecarpine: Impact on Src/FAK-Mediated Macrophage Migration

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.

Inhibitory Effect of Genomic DNA Extracted from Pediococcus acidilactici on Porphyromonas gingivalis Lipopolysaccharide-Induced Inflammatory Responses

“…MAPK pathways, such as ERK 1/2, p38 kinase, JNK, and NF-κB pathways, are known to be common inflammatory signaling pathways that cause the release of proinflammatory cytokines, such as IL-1β, and consequently lead to inflammation ( Jayakumar et al, 2021 ). Therefore, the activation of MAPK and NF-κB was assessed in RAW 264.7 cells pretreated with or without gDNAs.…”

Anti-Inflammatory Mechanism of An Alkaloid Rutaecarpine in LTA-Stimulated RAW 264.7 Cells: Pivotal Role on NF-κB and ERK/p38 Signaling Molecules

“…Recent studies from our group have proven the antiplatelet mechanisms of Rut through suppressing phosphoinositide 3-kinase (PI3K)/Akt/MAPK [ 23 ], p38-mediated NF-κB activation [ 24 ], and PI3K/Akt/glycogen synthase kinase-3β (GSK3β) [ 23 ] signaling cascades. Another relevant study found that Rut diminishes LPS-induced migration by hindering the Src/FAK pathway [ 25 ]. In this study, we demonstrated that Rut inhibits inflammatory molecules including NO production, iNOS, COX-2, and IL-1β expression in LTA, a Gram-positive bacterial cell wall component, induced RAW cells.…”

Momordica charantia extracts obtained by ultrasound-assisted extraction inhibit the inflammatory pathways

“…Inflammatory proteins are regulated by the MAPK and NF-κB pathways. Several natural products from plant extracts regulate inflammatory proteins through regulation of the MAPK and NF-κB signaling pathways (Jayakumar et al 2021;Chauhan et al 2022).…”

“…Furthermore, NF-κB can be activated via mitogen-activated protein kinases (MAPKs), such as c-Jun NH 2 -terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38, which are regulated by mitogen-activated protein kinase (MEK) (Hoesel et al 2013). It has been reported that various natural compounds derived from medicinal plants are effective in the treatment of inflammatory diseases through regulation of the related signaling pathways (Jayakumar et al 2021;Chauhan et al 2022).…”