Up-regulation of HIF-1α expression induced by ginkgolides in hypoxic neurons

Hypoxia-inducible factor-1 (HIF-1) is a master regulator of cellular and systemic oxygen homeostasis. Recently, we demonstrated that ginkgolides, the main constituents of the non-flavone fraction of the standardized Ginkgo biloba (Ginkgoaceae) extract EGb 761, have a significant protective role against chemical and physical hypoxia-induced injury in neurons and PC12 cells. Based on the findings and the function of HIF-1 as a master regulator of oxygen homeostasis, we speculate that the protective role of ginkgolides might be mediated by HIF-1. In this study, we therefore investigated the effects of ginkgolides on the expression of HIF-1 alpha, the cell viability and the lactate dehydrogenase (LDH) release in the hypoxic cortical neuron. We demonstrated that ginkgolides significantly increase the expression of HIF-1a and the cell viability as well as decrease the release of LDH in the hypoxic neuron. The findings suggested that the neuroprotective role of ginkgolides against hypoxia-induced injury might be associated with its role to up-regulate the expression of HIF-1a in the hypoxic neurons. (c) 2007 Elsevier B.V. All rights reserved.