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Neuroprotective effect of wogonin in hippocampal slice culture exposed to oxygen and glucose deprivation

https://doi.org/10.1016/j.ejphar.2004.04.017Get rights and content

Abstract

A poor supply of oxygen and glucose to the brain can cause severe brain damage. Therefore, neuroprotective drugs against ischemia need to be developed. In this study, wogonin, a flavone found in Scutellaria baicalensis, had a protective effect on neuronal cells damaged by oxygen and glucose deprivation in rat hippocampal slices in culture. In particular, the protective effect on the pyramidal cell layer was significant. On the basis of these experimental results, wogonin may be a therapeutic agent for treating ischemia in patients.

Introduction

The brain is an organ that requires a large amount of energy for its physiological functions. For this reason, the brain consumes 20% of inhaled oxygen. A poor supply of oxygen and glucose causes serious injury to neuronal cells. In particular, the hippocampus is the brain region the most vulnerable to hypoxia, and the loss of hippocampal neurons results in learning and memory impairments. Therefore, the development of neuroprotective drugs against ischemia is urgently required.

Scutellaria baicalensis is used in Korea to treat bacterial infection of respiratory and gastrointestinal tract, and diverse inflammatory diseases in Korea. Interestingly, recent experimental results have suggested that S. baicalensis has neuroprotective effects. S. baicalensis prevented neuronal cell death in the hippocampal CA 1 region induced by a four-vessel occlusion (Kim et al., 2001b) and attenuated apoptosis by inhibiting protein oxidation in a H2O2-treated neuronal cell line (Choi et al., 2002). These reports suggest that some compound(s) contained in S. baicalensis have neuroprotective effects. Flavones are believed to be the major biologically active agents. Among the flavones of S. baicalensis, wogonin, 5,7-dihydroxy-8-methoxyflavone, has been reported to show anti-oxidant, anti-inflammatory and anxiolytic effects Gao et al., 1999, Wakabayashi and Yasui, 2000, Shen et al., 2002, Hui et al., 2002. However, the neuroprotective effect of wogonin remains unknown.

This study investigated whether wogonin protects neuronal cells from injury caused by oxygen and glucose deprivation in a hippocampal slice culture.

Section snippets

Materials

α-Modified Eagle Medium (α-MEM), a penicillin/streptomycin solution, Hank’s balance salt solution (HBSS) and horse serum were purchased from Gibco BRL (Grand Island, NY, USA). Wogonin was obtained from Waco Pure Chemicals (Osaka, Japan). Propidium iodide (PI), d-glucose, and all the other chemicals were purchased from the Sigma (St. Louis, MO, USA).

Organotypic hippocampal slice culture

Hippocampal slices were prepared and cultured according to a modified interface culture method (Noraberg et al., 1999). Sprague–Dawley rats (7 days

Evaluation of neuronal cell death in oxygen and glucose deprivation injured hippocampal slice culture

In our experiment, cell death was observed after 35–40 min of deprivation of oxygen and glucose. Cell death was detected in the CA 1 region when the hippocampal slice was exposed for 35 min; however, cell death was observed in the whole hippocampal cell layer after exposure for 40 min (Fig. 1). In order to determine whether or not wogonin had a region-specific protective effect, the effect of wogonin on neuronal cell survival was observed in slices deprived of oxygen and glucose for 40 min.

Neuroprotective effect of wogonin in oxygen and glucose deprivation injured hippocampal slice culture

Cell

Discussion

Because of relevance to in vivo systems, much attention has been focused on the use of slices in culture for investigating pathophysiological events in the brain. Frotscher et al., 1995, Gahwiler et al., 1997, Stoppini et al., 1991. Recently, a large number of agents have been examined for their neuroprotective effect against oxygen and glucose deprivation in hippocampal slices in culture. Lithium reduced the ratio of phosphorylated heat shock protein 27 (HSP 27) to total HSP 27 and afforded

Acknowledgments

This work was supported by a grants of the Oriental Medicine RD project, Ministry of Health and Welfare, Republic of Korea (HMP-00-CO-04-004) and the Brain Korea 21 project (Korean Ministry of Education, Korea).

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