EGb761 Protects Hydrogen Peroxide-induced Death of Spinal Cord Neurons through Inhibition of Intracellular ROS Production and Modulation of Apoptotic Regulating Genes

Abstract

The present study was conducted to investigate whether Ginkgo biloba extract (EGb) 761 could protect spinal cord neurons from H(2)O(2)-induced toxicity. In primary spinal cord neurons isolated from embryonic day 14 rats, H(2)O(2) administration resulted in a significant decrease in the survival of spinal cord neurons. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and Hoechst 33342 nuclear staining showed that these cells die by apoptosis. Such neuronal death, however, was significantly reversed by EGb761 in a dose-dependent manner. Moreover, a marked increase in intracellular free radical generation was found after the H(2)O(2) administration which could be reversed almost completely by EGb761, indicating that inhibition of free radical generation is an important mechanism of the anti-apoptosis action of EGb761. Finally, treatment of cells with H(2)O(2) for 12 h reduced the expression of Bcl-2, an anti-apoptotic gene, by 70% but showed no effect on the level of Bax, a pro-apoptotic gene. EGb76 treatment, however, significantly reversed H(2)O(2)-induced reduction of Bcl-2 expression and inhibited Bax expression by 2.3-fold. Thus, our study provided evidence showing that the protective effect of EGb761 on spinal cord neuronal apoptosis after oxidative stress is mediated, at least in part, by its anti-oxidative action and regulation of apoptosis-related genes Bcl-2 and Bax.

Biphasic effect of EGb761 on simulated ischemia-induced rat BMSC survival in vitro and in vivo

“…The anti-oxidative effect was positively correlated with EGb761 concentration, which is consistent with other reports showing the anti-oxidative property of EGb761 in various cell lines (Jiang et al, 2009;Yeh et al, 2009).…”

“…The current data shows that EGb761 induces cell apoptosis via the caspase-9-mediated apoptotic pathway (Kim et al, 2005;Kotakadi et al, 2008). In our study, we found that low concentrations of EGb761 upregulated the expressions of caspase-9 and caspase-3, which consequently increased BMSC apoptosis, which was consistent with other reports (Jiang et al, 2009;Massieu et al, 2004). In contrast, high concentration of EGb761 inhibited activities of caspase-9 and caspase-3 and eventually significantly reduced BMSC apoptosis.…”

EGb761 improves histological and functional recovery in rats with acute spinal cord contusion injury

“…In addition, EGb761 has beneficial neuroprotective effects, probably by means of its antioxidant action, which involves the scavenging of free radicals. [10][11][12]17 In this study, we found that the number of apoptotic cells at 3 and 7 DPI in the EGb761-treated group was significantly smaller than that in the control group. HE-staining analysis further revealed that the cavity in the EGb761-treated group was significantly reduced.…”

Morroniside protects SK-N-SH human neuroblastoma cells against H2O2-induced damage

“…Exposure of cells to exogenous H 2 O 2 can induce ROS overproduction (30), leading to peroxidation of membrane lipids and disruption of cellular integrity (31). The present study showed that pretreatment with morroniside reversed H 2 O 2 -induced apoptosis by blocking ROS production.…”