SUPPRESSION OF LOCAL INFLAMMATION CONTRIBUTES TO THE NEUROPROTECTIVE EFFECT OF GINSENOSIDE Rb1 IN RATS WITH CEREBRAL ISCHEMIA

Local inflammation accounts for the progression of cerebral ischemic insult. Ginsenoside Rb1 (GRb1) is a natural product extracted from Panax ginseng C.A. Meyer. It has been reported to have beneficial effects in cerebral ischemia and to inhibit the inflammatory cascade in sepsis. In this study, to determine whether modulating local inflammation contributed to the neuroprotection of GRb1, male Sprague Dawley rats were treated with GRb1 or vehicle intranasally for 1 week before being subjected to temporary occlusion of the right middle cerebral artery and reperfusion. Neuroprotection of GRb1 was evaluated with a focus on the key elements of central nervous system (CNS) inflammation, such as inflammatory cells, proinflammatory cytokines, and transcriptional factor. GRb1 reduced infarction volume by 57% (n=6, P<0.01) and significantly alleviated the neurological deficit (n=12, modified neurological severity scores [mNSS]: 6.6 +/- 1.1 vs. 8.6 +/- 1.1, P<0.05). GRb1 depressed the activation of microglia in the penumbra by 15%-27% from 24 h to 72 h after reperfusion and its further convention into phagocytic microglia/macrophages. In GRb1 group, the peak mRNA level of tumor necrosis factor alpha (TNF-alpha) mRNA was decreased by 35% 12 h after reperfusion, whereas the protein level was significantly reduced by 43%-57%. Downregulation by GRb1 of both interleukin (IL)-6 gene and protein after GRb1 administration was also observed. GRb1 partially inhibited the activation of nuclear factor-kappa B (NF-kappa B) pathway from 6 h to 72 h after ischemia and reperfusion onset, as determined by the expression of total and phosphorylated NF-kappa B/p65, inhibitor protein of kappa B (I kappa B)-alpha, and I kappa B-kinase complex (IKK)-alpha. All these results indicate that suppression of local inflammation after cerebral ischemia might be one mechanism that contributes to the neuroprotection of GRb1. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.