Liuwei Anshen Capsule alleviates cognitive impairment induced by sleep deprivation by reducing neuroapoptosis and inflammation.

Ethnopharmacological Relevance: Cognitive dysfunction is a common complication of chronic insomnia. Liuwei Anshen Capsules (LAC), a traditional Chinese patent medicine clinically prescribed for insomnia, has been proved to possess good efficacy in reducing insomnia complications including dementia and anxiety in clinic. However, the active substances in LAC and their mechanisms in treating cognitive deficit associated with sleep disorders remain unclear.

Aim Of The Study: This study aims to explore the potential material basis and therapeutic mechanisms of LAC on cognitive impairment caused by sleep deprivation (SD) through an integrative approach combined serum pharmacochemistry, network pharmacology and experimental validation.

Methods: The active ingredients of LAC in vitro and in vivo were screened and identified by liquid chromatography-mass spectrometry (LC-MS) technology. The potential targets and signaling pathways of LAC against cognitive impairment were predicted based on network pharmacology and molecular docking. Subsequently, MWM and NOR were employed to evaluate the efficacy of LAC on cognitive impairment in SD rats, and the mechanism was further validated from pathological and molecular biology perspectives.

Results: Totally 85 active ingredients in LAC were accurately identified and 8 components absorbed into blood were found by LC-MS. Network pharmacology and molecular docking analysis predicted potential targets involving caspase-3, MAPK3, MAPK1, and Bcl-2. LAC (192, 384, and 768 mg/kg, i.g.) could improve spatial learning and memory of SD rats in a dose-dependent manner, restrain hippocampal neuronal apoptosis and microglia activation, and diminish TNF-α, IL-1β, and IL-6 expression levels, which achieved by regulating apoptosis-related proteins (caspase-3, Bax, and Bcl-2) and MAPK (p-ERK and p-P38) signaling pathway.

Conclusion: The findings provides evidence that LAC alleviates cognitive abnormality and pathological alterations in sleep-deprived rats by regulating the expression of apoptosis related proteins and MAPK signaling pathway, indicating its potential therapy for the cognitive complaints caused by insomnia or other neurological diseases.