Inhibition of human polymorphonuclear leukocyte responsiveness by penta-O-galloyl-β-D-glucose

Polymorphonuclear leukocyte (PMN) are suggested to be implicated in vascular and heart diseases [1]. In this study we analysed the effect of penta-O-galloyl-β-D-glucose on neutrophils-derived oxidants after receptor-mediated (N- formyl-methionyl-leucyl-phenylalanine; f-MLP) and non-receptor-mediated (phorbol-12-myristate-13-acetate; PMA) stimulation, as well as in the cell free assays. The anti-inflammatory potential of the compound was tested by determination the inhibition of release from activated neutrophils of elastase, myeloperoxidase (MPO), interleukin-8 (IL-8) and leukotreine B4 (LTB4) which are considered relevant to the pathogenesis of cardiovascular diseases. Penta-O-galloyl-β-D-glucose strongly inhibited reactive oxygen species production, in comparison with vitamin C, with IC50=0.2±0.1µM and 1.0±0.5µM for f-MLP and PMA stimuli, respectively. In cell free systems O-2 and H2O2 were significantly scavenged by PGG (IC50=2.2±0.5µM and 0.8±0.2µM). PGG were also a potent scavenger of HClO (IC50=11.2±0.1µM). Incubation of stimulated neutrophils with penta-O-galloyl-β-D-glucose (5–50µM) reduced in concentration-dependent manner the release of elastase and myeloperoxidase, IC50 value of 17±1µM and 15±1µM, respectively. The release of chemoattractant factors such as IL-8 and LTB4 was also affected. These results indicate that penta-O-galloyl-β-D-glucose down-regulated the PMN responsiveness and may provide a protective effect against vascular and heart diseases.

References: 1. Ernst, E, et al. (1987) JAMA 257: 2318–2324.