Abstract
BackgroundIn vivo studies have shown grape seed-derived polyphenols (GSP) to benefit in recovery from muscle injury by modulation of neutrophil infiltration into damaged tissue, thereby reducing secondary damage, as well as by facilitating an early anti-inflammatory macrophage phenotype shift. The current study aimed to provide data in this context from human models and to elucidate specific molecular targets of GSP.Using a placebo-controlled, double-blind study design, eighteen normally healthy volunteers between the ages of 18–35 years old (13 female and 5 male) were orally supplemented with 140 mg/day of GSP for 2 weeks.Blood samples (days 0 and 14) were comprehensively analysed for in vitro neutrophil chemokinetic capacity towards a chemotaxin (fMLP) using a novel neutrophil migration assay, in combination with live cell tracking, as well as immunostaining for neutrophil polarisation factors (ROCK, PI3K) at migration endpoint. Macrophage phenotype marker expression was assessed using flow cytometry.ResultsfMLP induced significant chemokinesis (P < 0.01), validating our model. GSP did not exert a significant effect on neutrophil chemokinesis in this non-compromised population, but tended to decrease overall ROCK expression in fMLP-stimulated neutrophils (P = 0.06). Macrophage phenotype markers CD274 and MPO – indicators of a pro-inflammatory M1 phenotype – seemed to be normalised relative to baseline expression levels after GSP treatment.ConclusionsCurrent data suggest that GSP may have a modulatory effect on the ROCK-PI3K-PTEN system, but results in this normal population is not conclusive and should be confirmed in a larger, more inflamed population. Potential modulation of macrophage phenotype by GSP should be investigated further.
Highlights
In vivo studies have shown grape seed-derived polyphenols (GSP) to benefit in recovery from muscle injury by modulation of neutrophil infiltration into damaged tissue, thereby reducing secondary damage, as well as by facilitating an early anti-inflammatory macrophage phenotype shift
We have previously shown in pre-clinical investigations in rodents, that GSP altered neutrophil migration into injured tissue, thereby limiting secondary damage and the magnitude of the total inflammatory response [7, 11, 12]
Neutrophil migration Representative images are presented for the placebo- and GSP-treated groups (Fig. 2a-h)
Summary
In vivo studies have shown grape seed-derived polyphenols (GSP) to benefit in recovery from muscle injury by modulation of neutrophil infiltration into damaged tissue, thereby reducing secondary damage, as well as by facilitating an early anti-inflammatory macrophage phenotype shift. Since the anti-inflammatory effects of grape-derived products have received relatively less attention in terms of research, despite the well-known links between oxidative stress and inflammation, this was a particular focus of the current study. In an in vitro model of HIV-associated neuroinflammation, GSP was shown to limit both pro-inflammatory cytokine secretion and chemotaxin-induced human monocytic cell migration across the blood brain-barrier [13]. Together, these data suggest that GSP targets specific cellular sites to beneficially alter the course of inflammation. To our knowledge, these effects have not been investigated in an in vivo human model and information on specific molecular targets of GSP remain limited
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