Abstract
Taurisolo® is a pomace extract from Aglianico Grapes, a wine cultivar native to Campania (Southern Italy). It exhibits a very high polyphenolic content and, consumed as a nutraceutical, is effective in reducing the level of Trimethylamine N-oxide (TMAO), a cardiovascular disease risk factor marker. We here show the effects of Taurisolo® on rat brain microvascular alterations induced by a diminution in cerebral blood flow (CBFD) for 30 min, due to bilateral common carotid artery occlusion, and subsequent blood flow restoration (CBFR) for 60 min. The rat pial microcirculation was investigated by intravital fluorescence microscopy through a parietal closed window implanted into the skull bone. The rat pial arterioles were classified according to Strahler’s ordering scheme, from smaller penetrating arterioles up to the larger ones. Western blotting analysis and mass spectrometry (MS)-based metabolomics were used to investigate the expression of endothelial nitric oxide synthase (eNOS) or the presence of peroxidized cardiolipin and several inflammatory mediators, respectively. Radical Oxygen Species (ROS) formation and neuronal loss were assessed. In rats CBFD and CBFR caused a decrease in arteriolar diameter, increase in fluorescent leakage and in adhesion of leukocytes to venular walls, reduction in the length of perfused capillaries and increment of ROS formation with large infarct size. Taurisolo®, intravenously or orally administered, induced pial arteriolar dilation (up to >30% of baseline), prevented fluorescent leakage, adhesion of leukocytes, ROS formation, while facilitated capillary perfusion and significantly reduced infarct size. These effects were accompanied by an increase in eNOS expression. Mass-spectrometry metabolomics analysis detected a marked decrease in the amount of peroxidized cardiolipin and pronounced reduction in pro-inflammatory prostaglandins and thromboxane Txb2. Altogether, these results extend the nutraceutical potential of Taurisolo® and suggest their eligibility for preventing brain damage due to ischemia-reperfusion injury.
Highlights
Endogenous antioxidants, like melatonin and glutathione, have been shown to exert preventive effects on an ischemiareperfusion injury, a complication resulting from the rapid restoration of the blood flow supply after an ischemic insult (Lapi et al, 2011; Zhou et al, 2018)
Animals treated with Taurisolo, intravenously or orally administered, and subjected to CBFD and Restoration of cerebral blood flow (CBFR) showed neuronal damage significantly diminished when compared to the Hypo-reperfused group (H group) (Figures 2C,D, respectively)
The present data indicate that Taurisolo, a nutraceutical endowed with antioxidant activity, was effective in decreasing the damage to the brain microcirculation, induced by reduction and successive recovery of cerebral blood flow
Summary
Endogenous antioxidants, like melatonin and glutathione, have been shown to exert preventive effects on an ischemiareperfusion injury, a complication resulting from the rapid restoration of the blood flow supply after an ischemic insult (Lapi et al, 2011; Zhou et al, 2018). Plant extracts enriched in polyphenols (Brosková et al, 2013), epigallocatechin, epigallocatechin-3-gallate (ECCG; Aneja et al, 2004), oleuropein and malvidin (Lapi et al, 2015, 2016) have been included among the nutraceuticals endowed with a protective effect against ischemia-reperfusion injury. Their mechanisms of action have been mainly linked to their antioxidant potential and their ability to counterbalance oxidative stress (Zhou et al, 2018). Much evidence indicates that nutraceutical inhibits mitochondrial oxidative stress and ROS production resulting in a partial reduction of brain damage (Brosková et al, 2013)
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