| Objective to study effects of Cnidii Fructus coumarin constituent and its main ingredients total coumarin(CTC),bergapten,isopimpinellin the in hypnotic.To study effects of Cnidii Fructus coumarin constituent on the levels of neurotransmitters on insomnia rats induced by PCPA.Investigating the mechanism of the hypnotic effect of coumarin.Method The rat model of insomnia was established by intraperitoneal injection of PCPA(ALA).Meanwhile,gastric perfusion consecutively of Diazepam positive control group(3mg/kg),Cnidii Fructus total coumarin(CTC)(60mg/kg),bergapten(1.5mg/kg),isopimpinellin(1.5mg/kg)for 6 days.30 minutes after intragastric administration in third day,synergistic hypnotic dose of sodium pentobarbital(28 mg/kg)was injected for sleep incubation and sleep lasting time observation;Morris water maze experiment testing memory learning levels in rats.The single amine neurotransmitter in the brain stem,serotonin(5-HT)and 5-hydroxy indole acetic acid(5 HIAA),norepinephrine(NE),dopamine(DA),amino acid neurotransmitter gamma-aminobutyric acid(GABA)and the content of serum melatonin(MT)was tested by ELISA,analysis the effect of hypnogenesis of Cnidii Fructus total coumarin(CTC),bergapten and isopimpinellin on the neurotransmitter content and learning and memory in insomnia rats.Results1 Influence of Cnidii Fructus coumarin constituent sodium pentobarbital synergistic hypnotic on insomnia rats induced by PCPA:The sleep latency of model group was significantly higher than blank control group(P < 0.05),isopimpinellin,bergapten,CTC group was significantly lower than that of model group(P < 0.05,P <0.001);sleep duration model control group and the blank control group had no significant difference,isopimpinellin,bergapten,CTC group were significantly higher than the model group(P < 0.01,P < 0.001)and blank control group(P < 0.05).The results indicated that the sleep latency of PCPA rats was longer than that of normal rats,but the duration of sleep was not significantly different from that in normal rats.Isopimpinellin,bergapten,CTC significantly shorten the sleep latency,prolong the sleep duration.It has significant hypnotic effect on insomnia rats induced by PCPA.2 Effect of Cnidii Fructus coumarin constituent on insomnia rat induced by PCPA spatial learning and memory and cognition::the influence of model group navigation escape latency time is significantly higher than the blank control group(P < 0.001);The navigation control group significantly higher than the control group the percentage of edge model search strategy(P<0.05),As to group CTC is straight or linear trend,IS,BE group of multi edge type,The marginal percentage tended to decrease compared with the model control group,but there was no significant difference between the two groups;Space exploration,target time,target distance / total distance,model control group,and significantly lower than the blank control group(P < 0.05,P < 0.01),Space exploration strategy model contrast,IS,BE group was marginal,blank control,diazepam,CTC tended to be directional,The percentage of edge type model control group was significantly higher than control group(P < 0.05),CTC group of marginal percentage compared to the model control group decreased,but there was no significant difference.The results showed that IS and BE had no significant effect on spatial cognition and memory impairment in PCPA rats,CTC can improve the location,navigation and spatial exploration strategy of PCPA insomnia rats3 Effects of Cnidii Fructus coumarin constituent on monoamine neurotransmitters in brain stem of rats with insomnia:The brain stem 5-HT,5-HIAA content of model control group was significantly lower than the blank control group(P<0.05,P< 0.001),The content of 5-HIAA in brain stem of bergamot and CTC group was significantly higher than that in model control group(P< 0.05);The brain stem NE and DA content in model control group were significantly higher than that in blank control group(P< 0.05,P< 0.001),There was no significant difference in the contents of NE and DA in the brain stem of each treatment group.The results indicated that CTC and bergapten significantly increased the brain stem 5-HIAA content in PCPA rats with insomnia.4 Effects of Cnidii Fructus coumarin constituent on amino acid neurotransmitter in brain stem of rats with insomnia:The model of brain stem GABA content of controlgroup was significantly lower than the control group(P < 0.001),CTC,isopimpinellin,bergapten group was significantly higher than that in the model group(P < 0.001).It showed that CTC,isopimpinellin,bergapten significantly increased the content of GABA in hypothalamus of rats,have certain effect on the treatment of insomnia.5 Effects of Cnidii Fructus coumarin on serum MT in rats with insomnia:MT in serum of model group was significantly lower than the control group(P < 0.001),isopimpinellin,CTC group were significantly higher than the model group(P < 0.01,P <0.001).It showed that CTC,isopimpinellin significantly increase the level of serum MT in insomnia.rats induced by PCPA.Conclusion Cnidii Fructus coumarin constituent has significant hypnotic effect on insomnia rats induced by PCPA and has obvious role in promoting the spatial reference memory.The mechanism of action may correlate with the up-regulate 5-HIAA,GABA in brain stem and MT in serum. |
PDF Full Text Request