Antiapoptotic Effects of EGb 761

Table 1

Specific effects and mechanisms associated with EGb 761 administration in vivo in several models and the equivalent dosage for human.

Dosage of EGb 761	Experimental treatment	Tissue studied	Equivalent dose for human*	Effect	References
Traumatic spinal cord injury
100 mg/Kg i.g. SD rats	Daily, for 1, 7, 14, and 21 days after surgery	Spinal cord	112 mg	The percentage of iNOS-positive cells and apoptotic index of nerve cells in the EGb group was significantly lower than that in the control group, which suggested that EGb 761 suppressed iNOS expression and then prevented nerve cell death	[46]
Aging
100 mg/Kg in SD rats	Daily, for 4 and 12 months	Cochlea	112 mg	EGb 761 treatment significantly prevented aging-related caspase-3/7-induced activity. This result correlates with significant improvement of auditory steady state	[53]
2 mg/Kg in SAMP8 mice	Daily, for 3 and 9 months	Hippocampus and motor cortex	1.12 mg	The Bax/Bcl-2 expression ratio was significantly decreased in the 9-month-old hippocampus and in the 3-month-old motor cortex as compared with the control group	[58]
100 mg/kg in NMRI mice	Daily, for 14 days	Spleen	56 mg	The number of ROS-induced apoptotic cells was significantly reduced in the EGb 761 group	[45]
Ischemia
45 mg/kg, i.v. in SD rats	Just before reperfusion	Hippocampus	50 mg	EGb 761 treatment improved behavior score and enhanced the phosphorylations of Akt and CREB and the expression of BDNF	[116]
100 mg/Kg oral in SAMP8 mice	Daily, 3 days prior to surgery and further 4 days after	Frontal, parietal and temporal lobes, corpus striatum, cerebellum, and brainstem	56 mg	EGb 761 treatment significantly decreased Bax/Bcl-2 ratios as well as caspase-9 levels in all brain regions compared with control animals in both young and aged mice	[62]
100 mg/Kg in SD rats	One hour before the onset of MCAO	Cerebral cortex	112 mg	EGb 761 administration significantly decreased the number of TUNEL-positive cells and the ratio of Bcl-2 and Bax expression	[61]
100 mg/Kg in C57BLK/6 mice, HO-1^−/− knockout	After 1.5 and 4 h of permanent distal MCAO	Cerebral cortex	56 mg	Treatment with EGb 761 decreased infarct volume and improved neurologic deficit scores. This protective effect was lost in HO-1 knockout	[105]
100 mg/Kg p.o. in C57BLK/6 mice, HO-1^−/− knockout	Daily, for 7 days before induction of MCAO	Brain	56 mg	EGb 761 improved neurobehavioral function and decreased the infarct size. This effect was abolished in HO-1 knockout	[104]
Cardiovascular diseases
5 mg/Kg i.p. in SD rats	Three doses: One dose every 2 days for 6 days	Heart	5.6 mg	EGb 761 alleviated doxorubicin-induced cardiomyocyte apoptosis through stabilizing a cascade of mitochondrial-signalling effectors from p53, Bcl-2 proteins, cytochrome c, and mitochondrial potential to caspase-3 implicating the additional counteracting action of EGb 761 against doxorubicin apoptotic cardiotoxicity at multiple cellular levels	[55]
50 and 100 mg/Kg in Wistar rats	Daily, for 10 and 15 days	Aortic blood	56 and 112 mg	EGb 761 significantly increased the levels of polyunsaturated fatty acids in erythrocyte membranes, especially the eicosapentaenoic acid, and decreased the saturation index	[179]
Alzheimer’s disease
100 mg/Kg p.o. APPswe/PS1dE9 mice	Daily, for 30 days	Brain	56 mg	EGb 761 treatment had no effect on the size of existing senile plaques, but it had a straightening effect on curved neurites, indicating that neuronal plasticity is fast and still active in adult animals	[180]
100 mg/Kg in C57BL/6J and double transgenic TgAPP/PS1 mice	In diet for 30 days	Hippocampus	56 mg	EGb 761 reduced β-amyloid oligomers and restored CREB phosphorylation	[117]
100 mg/kg in SAMP8 mice	Daily, for 12 weeks	Hippocampus and platelets	56 mg	In platelets, EGb 761 protected against mitochondrial dysfunction, evaluated as cytochrome c oxidase activity, mitochondrial ATP and GSH content. In hippocampi, the protective effect of EGb 761 was observed only in old mice	[52]
Parkinson’s disease
40 mg/Kg i.p. in C57BL/6J mice	Daily, for 18 days	Striatum and midbrain	22.4 mg	EGb 761 administration upregulates the genes for tyrosine hydroxylase, vesicular monoamine transporter 2, dopamine transporter, dopamine D2 receptor, and transcription factors Pitx3 and Nurr1	[181]
40 mg/Kg i.p. in C57BL/6J mice	Daily, for 18 days	Striatum and substantia nigra pars compacta	22.4 mg	EGb 761 significantly attenuated MPTP-induced loss of striatal dopamine levels and tyrosine hydroxylase, blockade of lipid peroxidation, and downregulation of Mn-superoxide dismutase activity. Also, EGb761 improved MPTP-induced impairment of locomotion	[47]
Diabetes
25, 50, and 100 mg/kg i.p. in Wistar rats	Daily, for 14 days	Blood and liver	112, 28, and 56 mg	EGb 761 attenuated the increase of lipoperoxidation and urinary nitrite levels in comparison with control	[182]

∗The calculations of equivalent dose for human were according to Hernandez-Lopez [183]. The standard weight taken was of 70 kg. SD: Sprague-Dawley, MCAO: middle cerebral artery occlusion.