Anti-inflammatory effect of torilidis fructus ethanol extract through inhibition of Src

Abstract

Context: Torilidis fructus, fruits of Torilis japonica Decadolle (Umbelliferae), is a medicinal herb traditionally used as a pesticide, an astrictive, or a medicine for various inflammatory diseases. Objectives: Due to the lack of pharmacological studies on this herbal medicine, we explored the inhibitory activity of torilidis fructus on the macrophage-mediated inflammatory response using its ethanol extract (Tf-EE). Material and methods: The Griess assay and prostaglandin (PGE2) ELISA assay were conducted with Tf-EE (0-75 µg/mL) and LPS (1 µg/mL) treated RAW264.7 cells in cultured media. Tf-EE pretreated RAW264.7 cells were incubated with LPS for 6 h and semi-quantitative PCR was performed. Reporter gene assays, overexpression of target enzymes and immunoblotting were performed on macrophages to determine the molecular targets of Tf-EE. Results: Tf-EE markedly suppressed the inflammatory response of macrophages, such as lipopolysaccharide (LPS)-induced nitric oxide (NO) and PGE2 production with IC50 values of 35.66 and 62.47 µg/mL, respectively. It was also found that Tf-EE reduced the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 by 80%. Nuclear translocation and activation of nuclear factor (NF)-κB (p65 and p50) were declined by 60% and 30% respectively, and their regulatory events including the phosphorylation of AKT, IκBα, Src, and the formation of complexes between Src and p-p85 were also recognized to be diminished. Conclusions: The signalling events managed by Src and p85 complex seemed to be critically involved in Tf-EE-mediated anti-inflammatory response. This might suggest that Tf-EE exhibited anti-inflammatory effects through Src-targeted inhibition of NF-κB.

Mechanism investigation of fermented egg-milk peptides on colonic inflammatory diseases: based on in vivo and in silico research

“…SRC also plays vital roles in innate immunity, activation of immune cells, and production of inflammatory cytokines. 26 The activated SRC kinases could promote the inflammatory cells and pro-inflammatory cytokines, and also participate in the inflammatory signaling pathways, including MAPK, 27 NF-κB, 28 and PI3K pathways. 29 MMP9 plays an essential role in the pathogenesis of numerous disorders, especially with inflammatory etiology.…”

Trichosanthes tricuspidata Lour. Methanol Extract Exhibits Anti-Inflammatory Activity by Targeting Syk, Src, and IRAK1 Kinase Activity

“…ese results suggest that Tt-ME selectively inhibited LPS-induced inflammatory signaling in RAW2647 macrophages. Our recent findings reported that Syk and Src contribute to NF-κB-mediated phosphorylation of IκBα at early time points [38,49,50]. Meanwhile, MEK1/2, MKK3/6, TAK1, and IRAK1 are known to be the upstream molecules of ERK, JNK, and p38 [51][52][53].…”

Anti-Inflammatory Effects of Licania macrocarpa Cuatrec Methanol Extract Target Src- and TAK1-Mediated Pathways

“…Due to the functional response of Src in inflammatory signaling, inflammation-regulatory activities of Src including cytokine production, migration of macrophages, and inflammatory mediator production have been also found in LPS-treated macrophages [48, 49]. Several compounds or extracts with Src inhibitory property were also proved as anti-inflammatory reagents [14, 50–53]. In the AP-1 pathway, Lm-ME suppressed activation of only TAK1 and not IRAK1 and IRAK4 (Figure 3(e)).…”