Hydroxysafflor Yellow A Exerts Neuroprotective Effects by Inhibiting Protein Carbonyl Formation in Cerebral Ischemia-Reperfusion Injury.

Protein carbonylation by reactive oxygen species (ROS) is an important factor in the pathogenesis of cerebral ischemia-reperfusion injury (CIRI). Carbonyls are mainly produced by peroxynitrite (ONOO-) and hemin/hydrogen peroxide (H2O2)/sodium nitrite (NaNO2)-mediated reactions. As the main active watersoluble chalcone chemical ingredient derived from Carthamus tinctorius L, hydroxysafflor yellow A (HSYA) has been increasingly applied in the treatment of cerebrovascular disease (CVD). In this study, rats were randomly divided into 3 groups: the sham-surgery group (sham), the CIRI group (CIRI) and the CIRI treated with HSYA group (HSYA). We evaluated the protective properties of HSYA in a CIRI model in vivo, assessed its efficacy against ONOO- and hemin/H2O2 /NaNO2-induced oxidative damage to cerebral cortical tissues in vitro, and explored the probable molecular mechanisms underlying its neuroprotective effects. The results showed that HSYA protected rats against CIRI by improving their neurological function score (P < .05), reducing infarct volume (P < .01), decreasing the content of protein carbonyls (P < .01) and elevating the glutathione (GSH) levels (P < .01). Further in vitro investigations found that HSYA pretreatment could inhibit protein carbonylation induced by exogenous ONOO-application in cortical brain tissues in a dosedependent manner (P < .01). In terms of hemin/H2O2 / NaNO2-triggered oxidative damage, HSYA slightly promoted the formation of carbonyl groups (P < .05). In conclusion, this study demonstrates that the neuroprotective capabilities of HSYA in CIRI are attributable, at least in part, to the enhancement in antioxidant capacity and the attenuation of protein oxidation, probably via the combined processes of ONOO- scavenging and the suppression of protein carbonyl formation. [ABSTRACT FROM AUTHOR]