Due to their localization at the interface between blood and tissue, endothelial cells
are the first target of any change occurring within the blood, and alterations of
their functions can seriously impair organs. During hypoxia, which mimics in vivo
ischemia, a cascade of events occurs in the endothelial cells, starting with a decrease
in ATP content and leading to their activation and release of inflammatory mediators.
EGb 761 and one of its constituents, bilobalide, were shown to inhibit the hypoxia-induced
decrease in ATP content in endothelial cells in vitro. Under these conditions, glycolysis
was activated, as evidenced by increased glucose transport, as well as increased lactate
production. Bilobalide was found to increase glucose transport under normoxic but
not hypoxic conditions. In addition, EGb and bilobalide prevented the increase in
total lactate production observed after 60 min of hypoxia. However, after 120 min
of hypoxia, the total lactate production was similar under normoxic and hypoxic conditions,
and both compounds increased this production. These results indicate that glycolysis
slowed down between the 60th and 120th minute of hypoxia, while EGb and bilobalide
delayed the onset of glycolysis activation. In another experimental model, both compounds
were shown to increase the respiratory control ratio of mitochondria isolated from
liver of rats treated orally. Since ischemia is known to uncouple mitochondria, the
protection of ATP content and the delay in glycolysis activation observed during hypoxia
in the presence of EGb 761 or bilobalide is best explained by a protection of mitochondrial
respiratory activity, at least during the first 60 min of hypoxia incubation. Both
products retain the ability to form ATP, thereby reducing the cell's need to induce
glycolysis, probably by preserving ATP regeneration by mitochondria as long as oxygen
is available.