Ginsenoside Rg1 promotes sleep in rats by modulating the noradrenergic system in the locus coeruleus and serotonergic system in the dorsal raphe nucleus

Abstract

Panax ginseng Mayer has been used as tranquilizer to improve sleep disorder, but its active component is not defined. This study investigated the effects of the most abundant constituents of P. ginseng—protopanaxatriol ginsenoside Rg1 and protopanaxadiol ginsenoside Rb1—on sleep in rats. Male Sprague-Dawley rats received intragastrical injections of Rg1 and Rb1 for 3 days (5, 10, and 20 mg/kg/day). Sleep parameters were analyzed using electroencephalogram and electromyogram. Neuronal activation and monoaminergic neurotransmitters were evaluated using immunohistochemical fluorescence staining and HPLC, respectively. Rg1 treatment significantly increased the duration of total sleep, rapid eye movement sleep (REMS) and Non-REMS at the dose of 5, 10 and 20 mg/kg/day, and also prolonged the proportion of slow-wave sleep in the total sleep. The Non-REMS episodes were increased and the mean duration of each wakefulness episode was depressed by Rg1 treatment. Rb1 had no effect on sleep parameters. Rg1 treatment decreased the activity of noradrenergic neurons in locus coeruleus (LC) and increased the activity of serotonergic neurons in the dorsal raphe nucleus (DRN). Besides, Rg1 depressed extracellular norepinephrine concentrations in both LC and DRN and in other sleep-regulating brain regions of which functions can be modulated by monoaminergic neurotransmitters discharged from projecting noradrenergic and serotonergic neurons. In conclusion, Rg1 might be the sleep-promoting component in P. ginseng and its mechanism may be related to the modulation of noradrenergic and serotonergic systems. Our findings also highlight functional differences between Rg1 and Rb1.

Keywords

• Ginsenoside Rg1
• Sleep
• Locus coeruleus
• Dorsal raphe nucleus
• Norepinephrine
• Serotonergic system