| Objective:Chrysanthemum is the dry capitulum of Compositae Plants Chrysanthemum morifolium Ramat.Chrysanthemum is sweet,bitter and slightly cold in nature with the advantages of calming liver,improving eyesight,clearing heat and detoxifying.“Compendium of Materia Medica” records: “chrysanthemums as pillows for eyesight” and folks often use chrysanthemum pillows to prevent insomnia,however,the role of chrysanthemums in treating insomnia is rarely studied.Kaifeng chrysanthemum has a long history,mainly researching on ornamental and cultivation,but less on the medicinal value of Kaifeng chrysanthemum.Sleep disorder is a common clinical disease and frequently-occurring disease,and the main manifestation is insomnia.This study explored the sedative-hypnotic effects and mechanisms of different extracts of Kaifeng Chrysanthemum KFC-6 on insomnia model mice.Methods:Research on KFC-6 of Chrysanthemum in Kaifeng.The water extract were extracted from dried Chrysanthemum by distilled water.The ethanol extract was extracted from dried Chrysanthemum by 95% ethanol.The volatile oil were extracted from dried Chrysanthemum by steam distillation.Intraperitoneal injection of PCPA was used to prepare an insomnia mice model.Administration of intragastric and inhalati were used to explore the sedative and hypnotic effects of different extracts of Kaifeng Chrysanthemum KFC-6 by locomotor activity test and pentobarbital sodium-induced sleep test in mice,to investigate the effects of different extracts of Kaifeng Chrysanthemum KFC-6 on body temperature,learning and memory function,motor coordination ability and muscle relaxation in insomnia model mice by temperature measurement,Morris water maze experiment,inclined plate experiment,and traction test and to explore the sedative-hypnotic mechanisms of different extracts of Kaifeng Chrysanthemum KFC-6 by measure the inflammatory factor levels of IL-1?,IL-6 and TNF-? in blood serum,the monoamine neurotransmitter levels of 5-HT,5-HIAA,NE and DA in brain tissue and the amino acid neurotransmitter levels of Glu and GABA in brain tissue by ELISA Kits.Results:The water extract,ethanol extract and volatile oil of Kaifeng Chrysanthemum KFC-6 could reduce the number of locomotor activity and extend the sleep time of pentobarbital sodium induced sleep in mice with insomnia.The results were better in the WFC-H group and the INH-EO-H group.Compared with the model group,the number of locomotor activity was reduced to 82.90±36.48(P<0.05)and the sleep time of pentobarbital sodium induced sleep was extended to 153.80±23.05 min(P<0.01)in the WFC-H group;The number of locomotor activity was reduced to 86.29±32.65(P<0.05)and the sleep time of pentobarbital sodium induced sleep was extended to 169.90±30.29 min(P<0.001)in the INH-EO-H group.Compared with the model group,the stay time on the inclined plate was increased to 56.18±5.83 s(P<0.001),53.88±6.92 s,52.29±13.17 s(P<0.01)in the WFC-H,INH-EO-H group;The traction time in traction test was increased to 50.25±12.03 s(P<0.01),49.00±14.24 s(P<0.05)in the WFC-H,INH-EO-H group.Compared with the model group,the body temperature of mice in the WFC-H and INH-EO-H group did not change significantly and the WFC-H and INH-EO-H group no significant effect on the escape latency,the proportion of target quadrant swimming time and the times of crossing platforms in mice.Compared with diazepam group,WFC-H and INH-EO-H group had significantly increased residence time,traction time and number of platform crossings.The water extract,ethanol extract and volatile oil of Chrysanthemum KFC-6 could regulate monoamine and amino acid neurotransmitters in brain tissue.Compared with the model group,the level of 5-HT was increased to 120.89±8.33 ng/m L(P<0.001),118.59±7.91 ng/m L(P<0.001),the level of NE was reduced to 0.14±0.02 ng/m L(P<0.001),0.19±0.03 ng/m L(P<0.001)and the TNF-?(P<0.001)level of inflammatory factor in blood serum was reduced to 191.95±4.28 pg/m L(P<0.01),193.68.18±6.17 pg/m L(P<0.01)in the WFC-H,INH-EO-H group.In addition,compare with the model group,both WFC-H and INH-EO-H group were able to improve the level of Glu in brain tissue,but had no significant effect on the level of GABA.Conclusion:The water extract,ethanol extract and volatile oil of Kaifeng chrysanthemum KFC-6 has sedative-hypnotic effects,which can improve the motor coordination ability and muscle relaxation of insomnia model mice,and has no effect on body temperature and the function of learning and memory,among which WFC-H group and INH-EO-H group had the best sedative and hypnotic effects.The sedative and hypnotic effect of inhaled volatile oil was better than that of intragastric administration.Compared with diazepam and melatonin,WFC-H and INH-EO-H groups had no obvious adverse reactions and had certain advantages.Its mechanism of action may be realized by participating in 5-HT energy system,increasing 5-HT to improve slow-wave sleep,reducing NE level,increasing fast-wave sleep,inhibiting brain excitability,and reducing the function of maintaining arousal in the brain,and it may also be involved in sleep regulation mechanisms by lowering TNF-? levels. |
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