Preliminary Study On The Efficacy Of Chaiqin Jiangzao Decoction In The Treatment Of Primary Insomnia

Objective:Chai Qin Jiang Zao Decoction is Professor Liuqingquan’s experience in the treatment of primary insomnia.This prescription consists of Chaihu Guizhi Ganjiang Decoction and Suanzaoren Decoction.It consists of 10 Chinese herbal medicines including Chaihu,Huangqin,Ganjiang,Zhizi,Zhimu,Fuling,Guizhi,Chishao,Hehuanpi and Suanzaoren.With Ningxin Anshen,Shugan Jieyu effect.The clinical observation of Chai Qin Jiang Zao Decoction has been carried out in the previous period of this research group,confirming its curative effect on primary insomnia.In order to develop new prescription for Chai Qin Jiang Zao Decoction,this study conducted a preclinical study of Chai Qin Jiang Zao Decoction for treating primary insomnia,including the selection process of Chai Qin Jiang Zao Decoction,Chai Qin Jiang Zao Decoction for two kinds of insomnia.Observation of the efficacy of animal models,the influence of PCPA-induced neurotransmitters and brain cytokines contents in hypothalamus of rats with insomnia induced by PCPA,and acute toxicity test,preliminary study on the prescription-forming properties of Chai Qin Jiang Zao Decoction as a primary insomnia treatment prescription.Method:Selection and preparation of the extraction process: the extract of Chai Qin Jiang Zao Decoction was prepared by 3 process routes,and the suitable preparation technology was screened by comparing the hypnotic effect and acute toxicity.1、A total of 90 mice were randomly divided into 9 groups of 10 in each group,namely,No-treatment control group,Estazolam group,Zaoren Anshen Granule Group,and Chai Qin Jiang Zao Decoction 1 large and small dose group.Chai Qin Jiang Zao Decoction process 2 large,low-dose group,Chai Qin Jiang Zao Decoction process 3 large,low-dose group,each group of mice were intraperitoneal injection of a threshold dose of pentobarbital sodium.Record the mice’s sleep time.2、A total of 90 mice were grouped and administered as above,and each mouse was injected intraperitoneally with a subthreshold dose of pentobarbital sodium.Observe the number of mice falling asleep and calculate the rate of falling asleep.3、96 rats were randomly divided into 8 groups of 12 in each group.That is No-treatment group,PCPA model control group,Estazolam tablet group,Zaoren Anshen Granule group,Chai Qin Jiang Zao Decoction process 1,large-dose group,Chai Qin Jiang Zao Decoction process 3 large and small dose groups,continuous For 7 days,the animals were sacrificed and the weight of the hypothalamus was weighed and homogenized.The supernatant was removed after centrifugation at low temperature.The contents of IL-1β 、TNF-α in the brain of insomnia rats and the contents of 5-HT、5-HIAAA、Glu、GABA、DA、NE in the hypothalamus and the contents of IL-1β、TNF-α in the brain of the insomnia rats were observed after administration of the drug.The effects of the administration of the drug on the contents of IL-1β、TNF-α in the hypothalamus of the model rats and the contents of IL-1β、TNF-α in the brains of the insomnia rats were observed.4、Acute toxicity test60 rats were randomly divided into three groups according to body weight: the negative control group,Chai Qin Jiang Zao Decoction process group 1 and process 3 groups.The negative control group was given aseptic drinking water.The process group 1 and the process group 3 were intragastrically administered.Immediately after the administration,the animal’s response was observed,and the response of each rat and the number of animal deaths were recorded.The rats were continuously observed for 14 days.Results: 1、Chai Qin Jiang Zao Decoction process 1,process 3 large-dose group(28.66 g crude drug/kg)can significantly prolong the sleep time of the threshold dose mice(P <0.01),Chai Qin Jiang Zao Decoction process 2 large-dose group and small-dose compared with the blank control group,there was no significant difference in the effect of sleep time at the sodium perbititu threshold dose in mice(P>0.05),but the process 1 and process 3 pairs of extended threshold dose mice There was no significant difference in sleep time.2、Chai Qin Jiang Zao Decoction process 1 and technology 3 large and small doses(28.66,14.33 g crude drug/kg)group can increase the sleep rate of subthreshold mice(P<0.01);each dose of process 1 and process 3 There was no significant difference in the sleep rate of the group.the sleep rate of Chai Qin Jiang Zao Decoction process 2large and small doses is significantly lower than process 1 and process 3,The follow-up test cancelled the exploration of the 2 large and small dose group process.3、Compared with the No-treatment control group,the 5-HT content in the hypothalamus of the model group was significantly lower than that in the control group(P < 0.05),the content of 5-HIAA in the model group was significantly decreased(P < 0.05);The content of GABA in rat hypothalamus was decreased obviously,Glu content was increased(P < 0.05),and the GABA/Glu ratio of model group decreased;The content of IL-1β、TNF-α in hypothalamus and IL-1β、TNF-α in model group was significantly higher than that in control group(P < 0.01).Compared with the model group,Chai Qin Jiang Zao Decoction significantly increased the content of 5-HT and 5-HIAA in the hypothalamus of insomnia rats induced by PCPA(P <0.05),significantly increased GABA(P <0.05);The GABA/Glu ratio increases significantly(P <0.05).The Hypothalamus DA and NE(P <0.05)were significantly reduced,and the content of IL-1β and TNF-α in brain tissue was significantly reduced(P <0.05).4、Rat oral acute toxicity test(The maximum dose)After 14 days of observation,no rats died.No significant toxicity was observed except for the significant decrease in the body weight of the Chai Qin Jiang Zao Decoction group 1 during 1 week of administration and 2 weeks after the administration.Conclusion:Animal experiments show that Chai Qin Jiang Zao Decoction has hypnotic effect,and its mechanism may be related to the increase of 5-HT,5-HIAA and GABA content in hypothalamus,the content of Glu,DA and NE in hypothalamus,the reduction of the content of IL-1β and TNF-α of brain tissue,and the ability to increase the proportion of hypothalamus GABA/Glu.Chai Qin Jiang Zao Decoction Process 1,Craft 3 hypnotic effect is good,and high safety,suitable for Chai Qin Jiang Zao Decoction New Drug development.