Ziziphi Spinosae Semen(ZSS) has been used for treatment of insomnia in China for centuries. To reveal the influence of insomnia on the levels of the neurotransmitters including serotonin(5-HT), glutamic acid(Glu),γ-a...Ziziphi Spinosae Semen(ZSS) has been used for treatment of insomnia in China for centuries. To reveal the influence of insomnia on the levels of the neurotransmitters including serotonin(5-HT), glutamic acid(Glu),γ-aminobutyric acid(GABA),noradrenaline(NE) and dopamine(DA), and to study the role of ZSS aqueous extract in the treatment of insomnia, an UPLC-ESIMS/MS method was developed and validated for simultaneous determination of five neurotransmitters in the rat brain. The brain samples were pretreated by one-step direct protein precipitation with acetonitrile. The analytes were detected in positive mode with multiple reaction monitoring(MRM) and the procedure was completed in less than 10 min. The method showed a good linearity(R^2 >0.9967) with the other validation parameters were within acceptance range. The results indicated that the concentration of 5-HT, GABA and DA is significantly lower(P < 0.01) in para-chlorophenylalanine(PCPA)-induced insomnia rat model group, while Glu and NE significantly higher than those in control group(P < 0.01). Treatment with ZSS aqueous extract(4 or 8 g·kg^1·d^-1 for seven days) could ameliorate the symptoms of insomnia by significantly changing the levels of the neurotransmitter parameters mentioned above. The data obtained in this study demonstrate that ZSS aqueous extract could ameliorate the symptoms of insomnia by modulating the levels of monoamines and amino acid neurotransmitters in the brain.展开更多
Objective:To study the sedative and hypnotic effects and underlying mechanisms of Polygala tenuifolia(PT)on treating aged insomnia rats.Methods:Sixty Sprague-Dawley male rats were divided into 6 groups by a random num...Objective:To study the sedative and hypnotic effects and underlying mechanisms of Polygala tenuifolia(PT)on treating aged insomnia rats.Methods:Sixty Sprague-Dawley male rats were divided into 6 groups by a random number table,including control group,model group,diazepam group(0.92 mg/kg),as well as PT low-,medium-and high-dose groups(0.0875,0.175,0.35 g/kg,respectively),10 rats in each group.Aged insomnia rat model was established with subcutaneous injection of D-galactose for 42 days and then intraperitoneal injection of para-chlorophenylalanine for 3 days.PT and diazepam were respectively given to aged insomnia rats by intragastric administration for 7 days after model establishment.Then the rats were investigated by body weight,Morris water maze test,pentobarbital test,enzyme-linked immunosorbent assay,and transcriptome sequencing.Results:Compared with the model group,PT increased the body weight,improved memory ability,and prolonged pentobarbital-induced sleep time of aged insomnia rats(P<0.01 or P<0.05).The medium dose of PT also increased the neurotransmitter levels of 5-hydroxytryptamine(5-HT)and gamma-aminobutyric acid(GABA),and decreased the level of Glu in the hippocampus of aged insomnia rats(P<0.05 or P<0.01).Twenty-four differentially expressed genes(DEGs)were overlapped among model group,medium-dose PT group,and diazepam group in transcriptome analysis.Fuom and Pcp2 were down-regulated by the treatment of medium-dose PT(P<0.01 or P<0.05).The metabolic pathways of PT were relatively less than diazepam(91 vs.104).Conclusions:The sedative and hypnotic effects of PT in aged insomnia rats might be related to neuro,metabolism pathways,especially through GABAergic signaling pathway.It provided more effective herb choice for the treatment of senile insomnia.展开更多
基金supported by the Natural Science Foundation of State(Nos.81603289 and 81603251)the Base Program of the Joint Training Talents of Shanxi Province(No.2017JD01)the Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi province(No.201605D111004)
文摘Ziziphi Spinosae Semen(ZSS) has been used for treatment of insomnia in China for centuries. To reveal the influence of insomnia on the levels of the neurotransmitters including serotonin(5-HT), glutamic acid(Glu),γ-aminobutyric acid(GABA),noradrenaline(NE) and dopamine(DA), and to study the role of ZSS aqueous extract in the treatment of insomnia, an UPLC-ESIMS/MS method was developed and validated for simultaneous determination of five neurotransmitters in the rat brain. The brain samples were pretreated by one-step direct protein precipitation with acetonitrile. The analytes were detected in positive mode with multiple reaction monitoring(MRM) and the procedure was completed in less than 10 min. The method showed a good linearity(R^2 >0.9967) with the other validation parameters were within acceptance range. The results indicated that the concentration of 5-HT, GABA and DA is significantly lower(P < 0.01) in para-chlorophenylalanine(PCPA)-induced insomnia rat model group, while Glu and NE significantly higher than those in control group(P < 0.01). Treatment with ZSS aqueous extract(4 or 8 g·kg^1·d^-1 for seven days) could ameliorate the symptoms of insomnia by significantly changing the levels of the neurotransmitter parameters mentioned above. The data obtained in this study demonstrate that ZSS aqueous extract could ameliorate the symptoms of insomnia by modulating the levels of monoamines and amino acid neurotransmitters in the brain.
基金Supported by the National Natural Science Foundation of China(No.81960837 and 81560762)Xinjiang Uygur Autonomous Region Healthy Young Medical Science and Technology Talents Special Research Project(No.WJWY-201919)the 13th Five-Year Plan of Traditional Chinese M edicine Strategic Emerging Key Profession of Xinjiang。
文摘Objective:To study the sedative and hypnotic effects and underlying mechanisms of Polygala tenuifolia(PT)on treating aged insomnia rats.Methods:Sixty Sprague-Dawley male rats were divided into 6 groups by a random number table,including control group,model group,diazepam group(0.92 mg/kg),as well as PT low-,medium-and high-dose groups(0.0875,0.175,0.35 g/kg,respectively),10 rats in each group.Aged insomnia rat model was established with subcutaneous injection of D-galactose for 42 days and then intraperitoneal injection of para-chlorophenylalanine for 3 days.PT and diazepam were respectively given to aged insomnia rats by intragastric administration for 7 days after model establishment.Then the rats were investigated by body weight,Morris water maze test,pentobarbital test,enzyme-linked immunosorbent assay,and transcriptome sequencing.Results:Compared with the model group,PT increased the body weight,improved memory ability,and prolonged pentobarbital-induced sleep time of aged insomnia rats(P<0.01 or P<0.05).The medium dose of PT also increased the neurotransmitter levels of 5-hydroxytryptamine(5-HT)and gamma-aminobutyric acid(GABA),and decreased the level of Glu in the hippocampus of aged insomnia rats(P<0.05 or P<0.01).Twenty-four differentially expressed genes(DEGs)were overlapped among model group,medium-dose PT group,and diazepam group in transcriptome analysis.Fuom and Pcp2 were down-regulated by the treatment of medium-dose PT(P<0.01 or P<0.05).The metabolic pathways of PT were relatively less than diazepam(91 vs.104).Conclusions:The sedative and hypnotic effects of PT in aged insomnia rats might be related to neuro,metabolism pathways,especially through GABAergic signaling pathway.It provided more effective herb choice for the treatment of senile insomnia.
