Neuroprotective effects of ginsenoside Rb1 on transient cerebral ischemia in rats

• Published in: Brain research 2007-09, Vol.1167, p.1-12
• Main Authors: Yuan, Q.-L, Yang, C.-X, Xu, P, Gao, X.-Q, Deng, L, Chen, P, Sun, Z.-L, Chen, Q.-Y
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Apoptosis - genetics; Apoptosis Regulatory Proteins - drug effects; Apoptosis Regulatory Proteins - metabolism; bcl-2/bax; Biological and medical sciences; Brain Ischemia - drug therapy; Brain Ischemia - metabolism; Brain Ischemia - physiopathology; Cell Count; Female; GDNF; Gene Expression Regulation - drug effects; Gene Expression Regulation - genetics; Ginsenoside Rb1; Ginsenosides - pharmacology; Ginsenosides - therapeutic use; Glial Cell Line-Derived Neurotrophic Factor - drug effects; Glial Cell Line-Derived Neurotrophic Factor - genetics; Glial Cell Line-Derived Neurotrophic Factor - metabolism; Infarction, Middle Cerebral Artery - drug therapy; Infarction, Middle Cerebral Artery - metabolism; Infarction, Middle Cerebral Artery - physiopathology; Ischemic Attack, Transient - drug therapy; Ischemic Attack, Transient - metabolism; Ischemic Attack, Transient - physiopathology; Male; Medical sciences; NAIP; Neurology; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Rats; Rats, Wistar; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Transient cerebral ischemia; TUNEL staining; Up-Regulation - drug effects; Up-Regulation - genetics; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2007.06.024

Abstract Previous experiments showed that ginsenoside Rb1 (GRb1) reduced infarct and neuronal deficit in rats followed by transient cerebral ischemia. The mechanism of this neuroprotective function is unclear. Here, we tested whether the effect of GRb1 can be achieved through preventing ischemic neuronal death, modulating apoptotic-related genes and affecting glial-derived neurotrophic factor (GDNF) expression in rats subjected to occlusion of the middle cerebral artery. When GRb1(40 mg/kg, i.p.) was administered immediately after reperfusion, the apoptotic cells in the GRb1 group were decreased significantly from 12 to 72 h of reperfusion compared to the ischemia group by TdT-mediated dUTP–biotin nick-end labeling. Immunostaining and Western blotting analysis showed that the expression of GDNF from 3 to 120 h of the GRb1 group was significantly increased compared to the ischemia group, and GDNF expression peaked at 48 h after reperfusion. The enhanced GDNF mRNA in the GRb1 group was not detected by RT-PCR and in situ hybridization compared to the ischemia group, but GDNF mRNA at 48 h after reperfusion was strongly increased in both the ischemia and GRb1 group when compared to other time points. The number of bcl-2-positive cells was significantly increased from 12 to 120 h of reperfusion compared to the ischemia group. However, the number of bax-positive cells in the GRb1 group was significantly declined compared to the ischemia group. In the GRb1 group, the number of neuronal apoptosis inhibitory protein-positive cells from 12 to 120 h after reperfusion was evidently higher than that in the ischemia group. Therefore, ginsenoside Rb1 prevents ischemic neuronal death induced by transient cerebral ischemia, and this mechanism of which is related to increase the expression of the antiapoptotic genes and modulate the expression of GDNF.