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

Zhu L, Wu XM, Yang L, Du F, Qian ZM

Institute for Nautical Medicine and Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, PRC; Laboratory of Iron Metabolism, Department of Applied Biology and Chemical Technology and National Key Laboratory of Chinese Medicine and Molecular Pharmacology (Shenzhen), Hong Kong Polytechnic University, Kowloon, Hong Kong.

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-1alpha, the cell viability and the lactate dehydrogenase (LDH) release in the hypoxic cortical neuron. We demonstrated that ginkgolides significantly increase the expression of HIF-1alpha 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-1alpha in the hypoxic neurons.

Published 27 August 2007 in Brain Res, 1166: 1-8.
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