interleukin-8 and shogaol

The proinflammatory chemokine interleukin-8 is increased in asthmatic patients. Traditionally, ginger is used as an antiinflammatory drug. An extract and several compounds of Zingiber officinale (ginger) were tested in human bronchial epithelial cells (BEAS-2B cells) with respect to their effect on lipopolysaccharide (LPS)-induced secretion of the proinflammatory chemokine interleukin 8 (IL-8) and RANTES (regulated upon activation, normal T-cell expressed and secreted). An oily extract of ginger rhizome with > 25% total pungent compounds, ginger volatile oil, ar-curcumene and α-pinene reduced the LPS-induced IL-8 secretion (measured by a specific enzyme-linked immunosorbent assay), whereas a spissum extract, the pungents [6]-gingerol and its metabolite [6]-shogaol, and the terpenoids citral and β-phellandrene showed no effect. The LPS-induced slight increase of RANTES was reduced by volatile oil, ar-curcumene and α-pinene. There was no effect of LPS on TNF-α. Our results suggest that distinct ginger compounds could be used as antiinflammatory drugs in respiratory infections.

Topics: Anti-Inflammatory Agents; Bicyclic Monoterpenes; Bronchi; Catechols; Cell Line; Chemokine CCL5; Cyclohexane Monoterpenes; Cyclohexenes; Dose-Response Relationship, Immunologic; Enzyme-Linked Immunosorbent Assay; Epithelial Cells; Fatty Alcohols; Humans; Interleukin-8; Lipopolysaccharides; Monoterpenes; Plant Extracts; Plant Oils; Pseudomonas aeruginosa; Rhizome; Sesquiterpenes; Volatile Organic Compounds; Zingiber officinale

We previously demonstrated that 6-shogaol and 6-gingerol, two active compounds in ginger (Zingiber officinale), possess antiinvasive activity against highly metastatic hepatoma cells. The aims of this study were to evaluate the inhibitory effect and molecular mechanism underlying the transcription and translation of matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (uPA) in Hep3B cells as well as the antiangiogenic activity of 6-gingerol and 6-shogaol.. By gelatin zymography and luciferase reporter gene assays, we found that 6-gingerol and 6-shogaol regulate MMP-2/-9 transcription. Moreover, 6-gingerol directly decreased expression of uPA, but the 6-shogaol-mediated decrease in uPA was accompanied by up-regulation of plasminogen activator inhibitor (PAI)-1. 6-Gingerol and 6-shogaol concentrations of ≥ 10 μM and ≥ 2.5 μM, respectively, significantly inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) and PI3K/Akt signaling, the activation of NF-κB, and the translocation of NF-κB and STAT3. Incubation of 6-gingerol or 6-shogaol with human umbilical vein endothelial cells or rat aortas significantly attenuated tube formation.. 6-Shogaol and 6-gingerol effectively inhibit invasion and metastasis of hepatocellular carcinoma through diverse molecular mechanisms, including inhibition of the MAPK and PI3k/Akt pathways and NF-κB and STAT3 activities to suppress expression of MMP-2/-9 and uPA and block angiogenesis.

Topics: Angiogenesis Inhibitors; Animals; Carcinoma, Hepatocellular; Catechols; Fatty Alcohols; Humans; Interleukin-8; Liver Neoplasms; MAP Kinase Signaling System; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinases; NF-kappa B; Phosphatidylinositol 3-Kinases; Plasminogen Activator Inhibitor 1; Proto-Oncogene Proteins c-akt; Rats; STAT3 Transcription Factor; Tumor Cells, Cultured; Urokinase-Type Plasminogen Activator; Vascular Endothelial Growth Factor A