Ginsenoside RB1 Reduces Neurologic Damage, is Anti-Apoptotic, and Down-Regulates p53 and BAX in Subarachnoid Hemorrhage

Abstract

Stroke is the second leading cause of death worldwide and the number one cause of adult disability in the United States and Europe. A subtype of stroke, subarachnoid hemorrhage (SAH), accounts for 7% of all strokes each year and claims one of the highest mortalities and morbidities. Many therapeutic interventions have been used to treat brain injury following SAH but none have reached the level of effectiveness needed to clinically reduce mortality. Ginsenoside Rb1 (GRb1), a major component of the Chinese traditional medicine Panax Ginseng, has been shown to reduce ischemic brain injury and myocardial injury via anti-apoptotic pathways. In the present study, we investigated the use of GRb1 on SAH induced brain injury in rats. Four groups were used: sham, vehicle (SAH), low dose treatment (SAH+ 5mg/kg GRb1), and high dose treatment (SAH+ 20mg/kg GRb1). Post assessment included wall thickness and mean cross-section area of basilar artery were measured for evaluating cerebral vasospasm, Evans blue extravasations to assess blood brain barrier (BBB) permeability, immunohistochemistry and Western Blot analysis looking for specific pro-apoptotic markers, and tunnel staining for cell death assessment. In addition, mortality, neurological function and brain edema were investigated. The results showed that high dose GRb1 treatment significantly enlarged mean cross-sectional area and decreased wall thickness of basilar artery, reduced neurological deficits, brain edema, BBB disruption, and TUNEL positive cell expression. Same time, we found that the proteins expression of P53, Bax and Caspase-3 were significantly reduced, whereas the expression of bcl-2 was up-regulated in Rb1 treatment. The results of this study suggest that GRb1 could relieve cerebral vasospasm and potentially provide neuroprotection in SAH victims. The underlying mechanisms may be partly related to inhibition of P53 and Bax dependent proapoptosis pathway. More studies will be needed to confirm these results and determine its potential as a long term agent.

Controversies and evolving new mechanisms in subarachnoid hemorrhage

“…Recently studies have shown that anti-apoptotic drugs ameliorate negative outcomes after SAH in animal models (Zhou et al, 2004; Zubkov et al, 2002). Current anti-apoptotic therapies for SAH focus on the MAPK pathway (Cahill et al, 2007; Suzuki et al, 2010b), the tumor suppressor p53 (Chen et al, 2011a; Li et al, 2010), and hypoxia inducible factor-1 (HIF-1) target genes. Additionally, intravenous mesenchymal stem cell administration in vivo provided neuroprotective effects by ameliorating neural cell apoptosis in SAH animal models (Khalili et al, 2012).…”

Early Brain Injury, an Evolving Frontier in Subarachnoid Hemorrhage Research

“…The tumor suppressor gene, p53, also regulates apoptosis. In EBI after SAH, anti-apoptotic therapies have reported to ameliorate outcomes by targeting the MAPK pathway [62, 106, 114, 131], activating p53 [13, 16, 68, 76], and hypoxia inducible factor-1 (HIF-1) target genes by hyperbaric oxygen [84]. …”

Trends in Ginseng Research in 2010

“…Li et al . [45] found that the ginsenoside Rb1 from P. ginseng relieves cerebral vasospasms and potentially protects against stroke and subarachnoid hemorrhaging and that the underlying mechanism may be partly related to the inhibition of the p53- and Bax-dependent proapoptosis pathways by Rb1. Jovanovski et al .…”