NEUROPROTECTIVE EFFECT OF MAGNOLOL ON ORGANOTYPIC HIPPOCAMPAL SLICE CULTURES

Objectives: During hypoxia/ischemia injury, several intracellular metabolic events lead to the generation of oxygen free radicals, which are involved in a variety of cellular processes of apoptosis and necrosis. Thus, it would be expected that antioxidant could restore redox equilibrium and protect cell deaths from hypoxic-ischemic injury. The purpose of the present study was to investigate the neuroprotective effect and therapeutic window of magnolol, an antioxidant extracting from Magnolia officinalis, in an ex vivo model of hypoxia, organotypic hippocampal slice cultures.

Methods: Organotypic cultures of the hippocampus were made and the slices were kept in culture for 8–10 days before oxygen/glucose deprivation (OGD). Testing compounds (magnolol 10 and 100mM) and vehicle (polyethylene glycol) were added to medium 1h before and throughout the period of the OGD in the pre-treated group. The optimal concentration of magnolol in the pretreated group was chose to be added at 2, 4 and 6 hours respectively after the onset of OGD/reperfusion in the post-treated group for exploring the therapeutic window.

Results: The extent of neuronal damage reduced among the culture, especially the pyramidal cells in CA3 (P=0.016) and dentate gyrus (P=0.011), with 100 mM Magnolol treatment compared with the control. However, the PI fluorescence fails to show significantly reduction in the concentration of 10mM Magnolol treatment. Regard to the therapeutic window of Magnolol treatment, the neuroprotective effect persisted into the cultures of 4 hours after OGD.

Conclusion: Magnolol reduced neuronal death following OGD/reperfusion and preserved its neuroprotective effect until 4 hours after oxygen/glucose deprivation, implying a beneficial effect for treating hypoxia/ischemia injury.