Research: NIEVERGELT and COLLEAGUES,

Listed in Issue 190

Abstract

NIEVERGELT and COLLEAGUES, Institute of Biochemistry and Molecular Medicine, University of Bern, 3012 Bern, Switzerland profiled ginger constituents for robust effects on proinflammatory signalling and cytokine expression in a validated assay using human whole blood.

Background

The rhizome of ginger (Zingiber officinale) is employed in Asian traditional medicine to treat mild forms of rheumatoid arthritis and fever.

Methodology

The authors profiled ginger constituents for robust effects on proinflammatory signalling and cytokine expression in a validated assay using human whole blood.

Results

Independent of the stimulus used (LPS, PMA, anti-CD28 Ab, anti-CD3 Ab, and thapsigargin), ginger constituents potently and specifically inhibited IL-1beta expression in monocytes/macrophages. Both the calcium-independent phospholipase A(2) (iPLA(2))-triggered maturation and the cytosolic phospholipase A(2) (cPLA(2))-dependent secretion of IL-1beta from isolated human monocytes were inhibited. In a fluorescence-coupled PLA(2) assay, most major ginger phenylpropanoids directly inhibited i/cPLA(2) from U937 macrophages, but not hog pancreas secretory phospholipase A(2). The effects of the ginger constituents were additive and the potency comparable to the mechanism-based inhibitor bromoenol lactone for iPLA(2) and methyl arachidonyl fluorophosphonate for cPLA(2), with 10-gingerol/-shogaol being most effective. Furthermore, a ginger extract (2 mug/ml) and 10-shogaol (2 muM) potently inhibited the release of PGE(2) and thromboxane B2 (>50%) and partially also leukotriene B(4) in LPS-stimulated macrophages. Intriguingly, the total cellular arachidonic acid was increased 2- to 3-fold in U937 cells under all experimental conditions. Our data show that the concurrent inhibition of iPLA(2) and prostanoid production causes an accumulation of free intracellular arachidonic acid by disrupting the phospholipid deacylation-reacylation cycle.

Conclusion

The inhibition of i/cPLA(2), the resulting attenuation of IL-1beta secretion, and the simultaneous inhibition of prostanoid production by common ginger phenylpropanoids uncover a new anti-inflammatory molecular mechanism of dietary ginger that may be exploited therapeutically.

References

Nievergelt A, Marazzi J, Schoop R, Altmann KH, Gertsch J. Ginger phenylpropanoids inhibit IL-1beta and prostanoid secretion and disrupt arachidonate-phospholipid remodeling by targeting phospholipases A2. Journal of Immunology. 187(8): 4140-50 Oct 15 2011.

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