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

TL;DR

A mushroom extract called GMK helps protect the brain from injury and cognitive decline after a lack of blood flow and oxygen.

Contribution

This study is the first to show that GMK protects against global cerebral ischemia–reperfusion injury and cognitive deficits.

Findings

GMK improved learning and memory and protected brain neurons in rats after ischemia-reperfusion injury.

GMK reduced oxidative stress and cell death in brain cells exposed to oxygen-glucose deprivation and reoxygenation.

GMK modulated key signaling pathways related to redox balance and apoptosis in injured brain cells.

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.

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