Coptidis Rhizoma extract mitigates sleep deprivation-induced cognitive impairment and neurodegeneration: Insights into hormonal, glymphatic, and molecular mechanisms.

BACKGROUND: and Aim: Coptidis Rhizoma extract (CRE) is a traditional herbal medicine commonly used to treat insomnia and cognitive deficits. However, its protective effects and underlying molecular mechanisms in conditions such as sleep deprivation (SD) are not fully understood. EXPERIMENTAL PROCEDURE: This study intended to elucidate these mechanisms by combining functional assessments, imaging techniques, and genomic analyses in an animal model of sleep fragmentation-induced cognitive impairment. CRE's efficacy was compared with melatonin, an established neuroprotective agent. RESULTS AND CONCLUSION: Our results demonstrated that SD significantly impaired cognitive functions and induced oxidative stress, inflammation, and multiple forms of neuronal cell death. Additionally, SD disrupted growth hormone (Gh) and hemoglobin (Hb) synthesis, impaired glymphatic clearance, and promoted accumulation of amyloid β-peptide (Aβ1-42), collectively contributing to neuronal inflammation and degeneration. Oral administration of CRE (0.5-1.5 g/kg/day) and intraperitoneal melatonin (10 mg/kg/day) for 15 days effectively reversed these adverse effects by restoring Gh and Hb synthesis, TH- and DCX-positive neurons, and glymphatic function, reducing inflammation and neurodegeneration, and normalizing genes and proteins involved in neurotransmission, oxygen transport, DNA repair, cellular metabolism, structural integrity, and neuronal function. However, neither treatment restored the downregulated expression of Gh-related genes, indicating limited effects on hypothalamic-pituitary regulation. In conclusion, these findings highlight the potential therapeutic role of CRE in alleviating cognitive and physiological impairments caused by sleep deprivation.