Effects of Dictyophora indusiata on Cognitive Impairment and Associated Neurobiological Changes in Chronic Mild Stress Mouse Model

Chronic stress is associated with changes in cognitive performance involving oxidative stress and inflammatory responses. This study investigated the bioactive compounds, antioxidant and acetylcholinesterase (AChE) inhibitory activities, and potential effects of Dictyophora indusiata (D. indusiata) on cognitive performance in an unpredictable chronic mild stress (UCMS) mouse model. D. indusiata extracts contained phenolics, flavonoids, polysaccharides, and ergosterol. These extracts exhibited in vitro antioxidant and acetylcholinesterase (AChE) inhibitory activities. Oral administration of D. indusiata powder improved performance on cognitive tasks in UCMS mice, as assessed using the Y-maze test, novel object recognition test, and Morris water maze test. These improvements were accompanied by upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA expression, downregulated Kelch-like ECH-associated protein 1 (Keap1) mRNA expression, increased superoxide dismutase (SOD) and catalase (CAT) activities, and reduced malondialdehyde (MDA) levels in the frontal cortex and hippocampus, suggesting potential involvement of the Keap1–Nrf2 signaling pathway. Furthermore, D. indusiata reduced mRNA expression of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Taken together, these findings suggest potential involvement of antioxidant defense and inflammatory responses in the effects of D. indusiata on cognitive performance under chronic stress, while the relevance of in vitro AChE inhibition warrants further investigation.