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

• Published in: Pharmaceutical biology 2017-12, Vol.55 (1), p.2074-2082
• Main Authors: Park, Gyubyung, Kim, Eunji, Son, Young-Jin, Yoon, Deok Hyo, Sung, Gi-Ho, Aravinthan, Adithan, Park, Yung Chul, Kim, Jong-Hoon, Cho, Jae Youl
• Format: Article
• Language: English
• Subjects: AKT protein; Animals; Anti-Inflammatory Agents - isolation & purification; Anti-Inflammatory Agents - pharmacology; Apiaceae; Cyclooxygenase-2; Dose-Response Relationship, Drug; Enzyme-linked immunosorbent assay; Ethanol; Ethanol - pharmacology; Female; HEK293 Cells; Herbal medicine; Humans; Immunoblotting; Inflammatory diseases; Inflammatory mediators; Lipopolysaccharides; Macrophages; Male; Medicinal plants; Mice; Mice, Inbred BALB C; NF-κB; NF-κB protein; Nitric oxide; Nitric-oxide synthase; Nuclear transport; Phosphorylation; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Pregnancy; Prostaglandin E2; Prostaglandin endoperoxide synthase; Protein Kinase Inhibitors - isolation & purification; Protein Kinase Inhibitors - pharmacology; RAW 264.7 Cells; Reporter gene; src-Family Kinases - antagonists & inhibitors; src-Family Kinases - metabolism
• ISSN: 1388-0209; 1744-5116
• DOI: 10.1080/13880209.2017.1362011

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 (PGE 2 ) 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 PGE 2 production with IC 50 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.