INO10, a Chaga Mushroom Extract, Alleviates Alzheimer’s Disease-Related Pathology and Cognitive Deficits in 3xTg-AD Mice

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive impairment with amyloid-β (Aβ) accumulation, tau hyperphosphorylation, and neuroinflammation. Among these pathological features, microglial activation is hallmark of neuroinflammation. Chaga (<i>Inonotus obliquus</i>) extract has been traditionally used for its diverse pharmacological properties, including anti-inflammatory and neuroprotective effects. This study aimed to evaluate the therapeutic potential of INO10, an inotodiol-rich chaga extract, in murine BV2 microglial cells and a 3xTg-AD mouse model. In BV2 cells, INO10 significantly reduced LPS-induced expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), indicating its potent anti-inflammatory effects. Oral administration of INO10 significantly improved spatial memory in 3xTg-AD mice, as evidenced by increased spontaneous alternation in the Y-maze test. Furthermore, INO10 treatment attenuated neuroinflammation, as indicated by reduced microglial activation and downregulated expression of pro-inflammatory cytokines. In addition, immunohistochemical analysis confirmed that INO10 exhibited favorable bioavailability, supporting its potential as a neuroprotective agent. Histological analysis further revealed a reduction in Ab accumulation and tau phosphorylation in the hippocampus, accompanied by a marked decrease in neuroinflammatory markers. These findings suggest that INO10 effectively mitigates AD-related pathology by reducing Aβ deposition, tau hyperphosphorylation, and neuroinflammation, ultimately leading to cognitive enhancement. Given its multi-target neuroprotective properties, INO10 may serve as a promising natural compound for AD treatment. Further investigations are warranted to elucidate its precise mechanisms and clinical applicability.