Abstract
Objective:This study investigates the sleep-modulating effects of ginsenoside Rg1(Rg1,C42H72O14),a key bioactive component of ginseng,and elucidates its underlying mechanisms.Methods:C57BL/6J mice were intraperitoneally administered doses of Rg1 ranging from 12.5 to 100 mg/kg.Sleep parameters were assessed to determine the average duration of each sleep stage by monitoring the electrical activity of the brain and muscles.Further,orexin neurons in the lateral hypotha-lamus(LH)and corticotropin-releasing hormone(CRH)neurons in the paraventricular hypothalamic nucleus(PVH)were ablated using viral vector surgery and electrode embedding.The excitability of LHorexin and PVHCRH neurons was evaluated through the measurement of cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog(c-Fos)expression.Results:Rg1(12.5-100 mg/kg)augmented the duration of non-rapid eye movement(NREM)sleep phases,while reducing the duration of wakefulness,in a dose dependent manner.The reduced latency from wakefulness to NREM sleep indicates an accelerated sleep initiation time.We found that these sleep-promoting effects were weakened in the LHorexin and PVHCRH neuron ablation groups,and disap-peared in the orexin and CRH double-ablation group.Decreased c-Fos protein expression in the LH and PVH confirmed that Rg1 promoted NREM sleep by inhibiting orexin and CRH neurons.Conclusion:Rg1 increases the duration of NREM sleep,underscoring the essential roles of LHorexin and PVHCRH neurons in facilitating the sleep-promoting effects of Rg1.
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