Sedative and hypnotic mechanism of Naoxinshu on the balance of γ-aminobutyric acid and glutamate
OBJECTIVE To explore the sedative and hypnotic effects of Naoxinshu Oral Solution(NOS)and elucidate its potential mechanisms of action.METHODS Male Institute of Cancer Research(ICR)mice were randomized into six groups of control,eszopiclone,Tianma Capsules,high-dose NOS,medium-dose NOS and low-dose NOS.Animal analysis system was utilized for assessing the spontaneous activity.Additionally pentobarbital sodium-induced sleep experiment was conducted.The levels of γ-aminobutyric acid(GABA)and glutamate(Glu)in brain were measured by liquid chromatography-mass spectrom-etry.The activities of metabolic enzymes GABA transaminase(GABA-T)and glutamic acid decarboxylase(GAD),as well as protein and mRNA levels,were determined by enzyme-linked immunosorbent assay(ELISA),immunohistochemistry and quanti-tative real-time polymerase chain reaction(qRT-PCR).RESULTS NOS significantly lowered the number of spontaneous activi-ties(P＜0.05),enhanced the sleeping rate(P＜0.05),shortened sleep latency(P＜0.05)and prolonged sleep duration(P＜0.01).The sedative effects on spontaneous activity induced by NOS were reversed by GABAA receptor blockers of flumazenil and bicuculline(P＜0.01).Furthermore,NOS significantly elevated GABA level in frontal cortex and hippocampus and decreased Glu level(P＜0.05).Also NOS boosted GABA and depressed Glu in frontal cortex and hippocampus(P＜0.01).Concurrently,the activity and protein levels of GABA-T in hippocampus of mice treated with NOS declined while the activity and expression of GAD spiked(P＜0.05).CONCLUSION NOS exerts sedative and hypnotic effects through modulating the activ-ity and expression of GABA-T and GAD,as well as the levels of GABA and Glu.Thus it hints at a potential therapeutic role for NOS in the regulation of sleep and sedation.
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