Tricin 7-glucoside protects against experimental cerebral ischemia by reduction of NF-κB and HMGB1 expression

There have been several studies of nuclear factor-kappa B (NF-kappa B) and high-mobility group box1 (HMGB1) associated with the pathophysiology of cerebral ischemia. Tricin 7-glucoside, a major bioactive compound extracted from Sedum sarmentosum Bunge. The objectives of this study were to determine the effects of Tricin 7-glucoside on a cultured neuronal cell line, SH-SY5Y in vitro and experimental ischemic stroke in vivo. For oxygen-glucose deprivation (OGD) and tumor necrosis factor-alpha (TNF-alpha) stimulated SHSY5Y cell line in vitro, SH-SY5Y cells were incubated with Tricin 7-glucoside. For in vivo experiment, rats were subjected to middle cerebral artery occlusion (MACO) for 1 h, then followed by reperfusion for 23 h. Treatment of SH-SY5Y cells with Tricin 7-glucoside reduced the OGD-induced apoptosis and cytotoxicity, blocked TNF-alpha-induced NF-kappa B and I kappa B-alpha phosphorylation, and decreased HMGB1 expression. At doses higher than 50 mg/kg, Tricin 7-glucoside produced a significant neuroprotective potential in rats with ischemia and reperfusion (I/R). Tricin 7-glucoside (100 mg/kg) demonstrated significant neuroprotective activity even after delayed administration at 2 h and 4 h after I/R. Tricin 7-glucoside 100 mg/kg attenuated histopathological damage, decreased brain edema, inhibited NF-kappa B activation and reduced HMGB1 expression. These data show that Tricin 7-glucoside protects brain against I/R injury with a favorable therapeutic time-window by alleviating cerebral I/R injury and attenuating blood-brain barrier (BBB) breakdown, and its protective effects may involve HMGB1 and NF-kappa B signaling pathway. (C) 2011 Elsevier B.V. All rights reserved.