A Water Extract of Mixed Mushroom Mycelia Mitigates Cognitive Deficit and Oxidative Stress After Global Cerebral Ischemia-Reperfusion Injury.

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Citation abstract

BACKGROUND: GMK is a bioactive material newly identified from a water extract of mixed mushroom mycelia ( Phellinus linteus, Inonotus obliquus, and Ganoderma lucidum ). It has shown protective effects against glutamate-induced excitotoxicity and lipopolysaccharide-triggered neuroinflammation. However, whether GMK can ameliorate global cerebral ischemia-reperfusion injury (GCIRI) and its associated cognitive deficit remains to be elucidated.

METHODS: GCIRI was induced in male Sprague-Dawley rats by bilateral common carotid artery occlusion with hypovolemia (BCCAO/H). GMK (30 or 90 mg/kg, p.o.) was administered once daily for 14 days before surgery. Cognitive functions were evaluated using the Y-maze, Barnes maze, and passive avoidance tests. Hippocampal CA1 neuronal survival and glial activation were analyzed by cresyl violet staining and Iba1/GFAP immunohistochemistry. In parallel, PC12 cells were pretreated with GMK (100 or 200 μg/mL, 24 h) before oxygen-glucose deprivation and reoxygenation (OGD/R), and apoptosis (TUNEL, Bax/Bcl-2), oxidative stress markers (ROS, MDA, and NO), antioxidant enzymes including glutathione peroxidase (GPX) and catalase (CAT), and signaling proteins (p-ERK/ERK, iNOS) were examined.

RESULTS: GMK significantly ameliorated GCIRI-induced learning and memory impairments, protected CA1 pyramidal neurons, and reduced microglial and astrocytic activation. In OGD/R-challenged PC12 cells, GMK attenuated apoptosis, suppressed ROS, MDA, and NO production, normalized GPX and CAT activities, and favorably regulated p-ERK and iNOS pathways.

CONCLUSIONS: These findings suggest that GMK confers dose-dependent behavioral and histopathological protection against GCIRI, potentially by modulating redox- and apoptosis-related signaling (Bax/Bcl-2, GPX/CAT, and ERK/iNOS pathways), with more consistent effects at a higher dose.