The galactolipid (2S)-1,2-di-O-[(9Z,12Z,15Z)-octadeca-9,12,15-trienoyl]-3-O-beta-d-galactopyranosyl glycerol (1) isolated from dried and milled fruits of Rosa canina by bioassay-guided fractionation is an antiinflammatory agent with inhibitory effects on chemotaxis of human peripheral blood neutrophils in vitro. The inhibition of cell migration is not related to toxicity. The presence of 1 in rose hips may explain the clinically observed antiinflammatory properties of rose hip herbal remedies.
1 Of the four major phosphodiesterase 4 (PDE4) subtypes, PDE4A, PDE4B and PDE4D are widely expressed in human in¯ammatory cells, including monocytes and T lymphocytes. We explored the functional role of these subtypes using ten subtype-selective PDE4 inhibitors, each belonging to one of two classes: (i) dual PDE4A/PDE4B inhibitors or (ii) PDE4D inhibitors. 2 These compounds were evaluated for their ability to inhibit antigen-stimulated T-cell proliferation and bacterial lipopolysaccharide (LPS)-stimulated tumour necrosis factor a (TNFa) release from peripheral blood monocytes. 3 All compounds inhibited T-cell proliferation in a concentration-dependent manner; with IC 50 values distributed over an approximately 50 fold range. These compounds also inhibited TNFa release concentration-dependently, with a wider (*1000 fold) range of IC 50 values. 4 In both sets of experiments, mean IC 50 values were signi®cantly correlated with compound potency against the catalytic activity of recombinant human PDE4A or PDE4B when analysed by either linear regression of log IC 50 values or by Spearman's rank-order correlation. The correlation between inhibition of in¯ammatory cell function and inhibition of recombinant PDE4D catalytic activity was not signi®cant in either analysis. 5 These results suggest that PDE4A and/or PDE4B may play the major role in regulating these two in¯ammatory cell functions but do not rule out PDE4D as an important mediator of other activities in mononuclear leukocytes and other immune and in¯ammatory cells. Much more work is needed to establish the functional roles of the PDE4 subtypes across a broader range of cellular functions and cell types.
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