Gastrodia elata, Polygonatum sibiricum, and Poria cocos as a Functional Food Formula: Cognitive Enhancement via Modulation of Hippocampal Neuroinflammation and Neuroprotection in Sleep-Restricted Mice

<i>Gastrodia elata</i>, <i>Polygonatum sibiricum</i>, and <i>Poria cocos</i> are traditional Chinese herbs commonly used as both medicinal and food ingredients, traditionally believed to improve liver and kidney functions, replenish vital energy (qi) and blood, and mitigate stress-induced damage. These herbs are combined in the Compound Gastrodia elata Formula (CGEF), a functional food formulation. Amidst growing interest in functional foods, this study explores the cognitive-enhancing effects of CGEF, focusing on cognitive function improvement. Cognitive impairment was induced in ICR mice via chronic sleep restriction. Behavioral assessments including the Y-maze test, object recognition test, Morris water maze test, and Passive avoidance test, were conducted to evaluate CGEF's effects. Serum levels of inflammatory markers and oxidative stress were quantified while in rat hippocampus tissue expressions of inflammatory, apoptotic, and neuroprotective-related protein markers were analyzed by Western blotting. Neurotransmitter concentrations in both the hippocampus and prefrontal cortex were determined by LC-MS/MS. CGEF significantly alleviated cognitive impairments across all behavioral tests. The underlying mechanisms likely involve a reduction in oxidative stress and peripheral inflammatory factors, and suppression of the TLR2/MyD88/NF-κB signaling cascade in the hippocampus, thereby mitigating neuroinflammation and neuronal apoptosis. Furthermore, CGEF modulated the PI3K/AKT/GSK3β signaling pathway, potentially contributing to neuronal integrity and synaptic plasticity maintenance. CGEF also restored neurotransmitter balance and regulated tryptophan metabolism, further alleviating cognitive deficits associated with sleep disruption. These findings suggest CGEF's potential as a functional food for reversing cognitive impairments caused by chronic sleep restriction, primarily through its anti-inflammatory and neuroprotective effects.