Sophora flavescens alcohol extract ameliorates insomnia and promotes PI3K/AKT/BDNF signaling transduction in insomnia model rats

Abstract

Active ingredient of Sophora flavescens is reported to promote non-rapid eye movement (NREM) sleep. However, the role of Sophora flavescens alcohol extract in insomnia is elusive, which is addressed in this study, together with the exploration on its potential mechanism. An insomnia model of rats was established by para-chlorophenylalanine induction and further treated with SFAE or Zaoren Anshen capsule (ZRAS; positive control drug). Sleep quality and sleep architecture of rats were evaluated by the sleep test, electroencephalogram and electromyogram. The levels of monoamine neurotransmitters in rat hypothalamus were determined using ELISA, and the transduction of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/brain-derived neurotrophic factor (BDNF) signaling in the brain tissues of rats was examined by Western blot. SFAE and ZRAS increased the sleeping time and decreased the sleep latency of insomnia rats. SFAE reduced waking time and increased NREM and REM time, while changing power density of wakefulness, NREM sleep, and REM sleep in insomnia rats. SFAE and ZRAS upregulated levels of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid, and downregulated those of norepinephrine and dopamine in insomnia rats. Besides, SFAE and ZRAS elevated BDNF expression as well as the ratios of phosphorylated (p)-PI3K/PI3K and p-AKT/AKT. The role of SFAE in insomnia model rats was similar with that of ZRAS. SFAE reduces insomnia and enhances the PI3K/AKT/BDNF signaling transduction in insomnia model rats, which can function as a drug candidate for insomnia.