Hydroalcoholic Extract of Ashwagandha Improves Sleep by Modulating GABA/Histamine Receptors and EEG Slow-Wave Pattern in In Vitro - In Vivo Experimental Models

Withania somnifera (ashwagandha) has been used traditionally as a remedy for insomnia and to enhance cognitive function. The effects of ashwagandha extract (AE, 35% withanolide glycosides, Shoden(Ⓡ)) on the expression levels of γ-aminobutyric acid (GABA)(A)ρ1 and histamine H3 receptors in Rattus norvegicus glioblastoma (C6) cell lines were studied using semiquantitative reverse transcriptase-polymerase chain reactions. The effects of AE on sleep onset and duration were studied in Swiss albino mice using the pentobarbital-induced sleep model. Furthermore, the effects on nonrapid eye movement (NREM) and rapid eye movement sleep patterns were studied in Wistar rats with electroencephalogram (EEG) to support the improvement in sleep quality. There was an increase in gene expression levels of GABA(A)ρ1 receptor (1.38 and 1.94 folds) and histamine H3 (1.14 and 1.29 folds) receptors induced by AE at doses of 15 and 30 μg/mL compared to control. AE at doses of 10, 25, and 50 mg/kg body weight showed a significant decrease in time to sleep onset and increased total sleep duration in the pentobarbital-induced sleep model. At 50 mg/kg body weight dosage level, a 34% decrease (P<0.0001) in sleep onset time and 47% increase (P<0.0001) in sleep duration was observed. The EEG study showed significant improvement in alpha, beta, theta, delta, and gamma bands at doses of 10, 25, and 50 mg/kg body weight with delta waves showing increases of 30%, 46% (P<0.05), and 34%, respectively. The induction of sleep, GABA-mimetic action, NREM sleep, and the effects on slow-wave cycles support the calming property of AE in improving the quality of sleep.