Neuroprotective Effects of Bilobalide, a Component of Ginkgo biloba Extract (EGb 761®) in Global Brain Ischemia and in Excitotoxicity-induced Neuronal Death

Abstract

In this study, we compared the protective effect of bilobalide, a purified terpene lactone component of ginkgo biloba extract EGb 761, (definition see editorial) and EGb 761 against ischemic injury and against glutamate-induced excitotoxic neuronal death. In ischemic injury, we measured neuronal loss and the levels of mitochondrial DNA (mtDNA)-encoded cytochrome oxidase (COX) subunit III mRNA in vulnerable hippocampal regions of gerbils. At 7 days of reperfusion after 5 min of transient global ischemia, a significant increase in neuronal death and a significant decrease in COX III mRNA were observed in the hippocampal CA1 neurons. Oral administration of EGb 761 at 25, 50 and 100 mg/kg/day and bilobalide at 3 and 6 mg/kg/day for 7 days before ischemia progressively protected CA1 neurons from death and from ischemia-induced reductions in COX III mRNA. In rat cerebellar neuronal cultures, addition of bilobalide or EGb 761 protected in a dose-dependent manner against glutamate-induced excitotoxic neuronal death (effective concentration [EC (50)] = 5 microg/ml (12 microM) for bilobalide and 100 microg/ml for EGb 761. These results suggest that both EGb 761 and bilobalide are protective against ischemia-induced neuronal death in vivo and glutamate-induced neuronal death in vitro by synergistic mechanisms involving anti-excitotoxicity, inhibition of free radical generation, scavenging of reactive oxygen species, and regulation of mitochondrial gene expression.

An Overview of the Protective Effects of Chitosan and Acetylated Chitosan Oligosaccharides against Neuronal Disorders

“…The goal of neuroprotection is to limit neuronal dysfunction or death after CNS injury, in an attempt to maintain the highest possible integrity of cellular interactions in the brain, thus minimizing the disturbance to the neural function [41]. According to the mechanisms of neuroprotection, the neuronal disorders can be treated by using different neuroprotection agents [42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57], such as antioxidants [42,43] and anti-inflammatory factors [44,45]. …”

“…According to its mechanism, neuroprotection can be categorized into several mechanisms, such as: antioxidant (free radical trapper/scavenger) [42,43]; anti-inflammatory [44,45]; anti-excitotoxic [46]; apoptosis inhibitor [47]; gene expression modulator [48]; ion channel modulator [49,50]; metal ion chelator [51,52]; neurotrophic factor [53,54,55]; matrix metalloprotease inhibitor [56]; and combined mechanism (combining two mechanisms or more) [57]. …”

Vascular Contributions to Cognitive Impairment and Treatments with Traditional Chinese Medicine

“…A standardized extract of Ginkgo biloba (EGb 761) has been shown to exhibit potent antioxidative and antiplatelet effects and could effectively reduce damage from cerebral ischemia [76–81]. Besides, EGb 761 extract protected hippocampal neuronal and neuroglia cells against damage and enhanced the recovery of learning/memory impairments from cerebral ischemia/reperfusion in mice and rats [79–83]. Furthermore, the Ginkgo extract has been reported to improve memory deficits and cognitive dysfunctions in various experimental models of memory disorders such as chronic stress, aging, and Parkinson's disease (PD) [84–86].…”

Ginkgo biloba Extract Prevents Female Mice from Ischemic Brain Damage and the Mechanism Is Independent of the HO1/Wnt Pathway

“…EGb 761 treatment attenuated cognitive impairments and prevented CA3 hippocampal neuronal loss in OVX/stress subjected female rats, as was observed with estrogen replacement [29, 30]. EGb 761 is an effective antioxidant that has been shown to provide protection against cardiovascular and neurological disorders [31, 32]. Many groups, including ours, have previously shown that EGb 761 attenuates brain damage in male rodents after permanent, transient and global models of ischemia [15, 16, 33].…”