Objective: In this study, the neuroprotective effects of a water-soluble extract from culture medium of Ganoderma lucidum mycelia (WER) on oxidative stress-induced injury were examined using H₂O₂-treated PC12 cells. Additionally, we investigated both the acute and chronic effects of WER on brain necrosis and apoptosis induced by hypoxia/ischemia (H/I) followed by reoxygenation in mice.
Methods: Viability and apoptosis index of H₂O₂-treated PC12 cells were determined by 3,4,5-dimethylthiazol-2-yl (MTT) assay and TUNEL staining, respectively. H/I in mice was induced by unilateral ligation of carotid artery and exposure of 8%O₂ for 30 min. Twenty-four hours after H/I, neurological deficits, cerebral infarction volume, and apoptosis level were evaluated.
Results: WER–pretreated PC12 cells showed an increased viability evaluated by MTT assay compared to untreated cells. TUNEL staining indicated that WER induced a concentration-dependent decrease of the number of apoptotic cells. In the mouse model of H/I, acute (pre-H/I) treatment of WER (1 g/kg, p.o.) did not affect neurological deficits, total plasma oxidative stress, cerebral lipid peroxidation, and infarction volume assessed 24-h after reoxygenation. However, chronic treatment of WER (1 g/kg, p.o., for 7 days) significantly improved these parameters compared with distilled water-treated mice. Moreover, chronic treatment of WER decreased the levels of apoptosis in two brain areas, the sensori-motor cortex and the CA1 of the hippocampus, analyzed by TUNEL and cleaved caspase-3 immunostaining.
Conclusion: These results show that daily intake of WER relieves the cerebral ischemic injury, which may be attributed to decrease of oxidative stress.