Pharmacodynamic Studies Of Total And Monomeric Ffavonoids Of Murraya Paniculata Leaves On The Sedative And Hypnotic Effects

In recent years with the rapid economic development, the pace of lifeaccelerating and work pressure increasing, insomnia and its related disorders havegradually turned out to be a threat to the public health. Chemical synthetic drugs inthe treatment of insomnia can cause many adverse reactions, therefore seekingcomponents from natural drugs to improve sleep function is one of the hot topics inpharmaceutical research. Total flavonoids of murraya paniculata leaves (TFMP) andmonomeric flavonoids JA, JB were extracted from Rutaceae plant murrayapaniculata. The purpose of the experiment was to observe TFMP-53%, TFMP-85%and JA, JB whether have significant sedative and hypnotic effects. We measured therelated neurotransmitters in brains in order to explore its possible mechanisminitially. This study provides experimental evidence for the development of newdrugs from TFMP-53%, TFMP-85%and JA, JB.1. The sedative and hypnotic experiment of TFMP-53%, TFMP-85%1.1Spontaneous locomotor activity experiment96male ICR mice, were randomly divided into8groups: Control (0.5%CMC-Na), TFMP-53%(50,100,200mg/kg) group, TFMP-85%(50,100,200mg/kg) group, Estazolam (0.5mg/kg) group. After continuous administration for3drecord activities counts in5min, and then calculate inhibition rate. TFMP-53%andTFMP-85%100,200mg/kg could significantly reduce spontaneous activities.TFMP-53%200mg/kg and TFMP-85%100,200mg/kg could rise activityinhibition rate more than50%.1.2Direct sleep experiment96male ICR mice, were randomly divided into8groups: Control (0.5%CMC-Na), TFMP-53%(50,100,200mg/kg) group, TFMP-85%(50,100,200mg/kg) group, Estazolam (0.5mg/kg) group. Put each mouse into a single cageimmediately after administration, and then record sleeping number and the time tofall asleep in3h. Sleeping was not found in TFMP-53%, TFMP-85%, indicatingthat TFMP has no direct hypnotic effect.1.3Experiment of sleep induced by subthreshold dose of pentobarbital sodium96male ICR mice, were randomly divided into8groups: Control (0.5% CMC-Na), TFMP-53%(50,100,200mg/kg) group, TFMP-85%(50,100,200mg/kg) group, Estazolam (0.5mg/kg) group. Continuous administration for3dsubthreshold dose (20mg/kg) of pentobarbital sodium was injected afteradministration in50min. Record sleeping latency and sleeping number in30min tocalculate the rate of sleep. TFMP-85%100,200mg/kg could shorten sleepinglatency significantly. TFMP-85%200mg/kg could increase sleeping ratesignificantly. TFMP-53%200mg/kg could increase sleeping rate significantly.1.4Experiment of sleep induced by threshold dose of pentobarbital sodium96male ICR mice, were randomly divided into8groups: Control (0.5%CMC-Na), TFMP-53%(50,100,200mg/kg) group, TFMP-85%(50,100,200mg/kg) group, Estazolam (0.5mg/kg) group. Continuous administration for3d,threshold dose (40mg/kg) of pentobarbital sodium was injected after administrationin50min. Record sleeping latency, sleeping duration of each dose. TFMP-53%200mg/kg and TFMP-85%100,200mg/kg could shorten sleeping latency and prolongsleeping duration significantly.2. The sedative and hypnotic experiment of flavonoid monomers JA, JB2.1Spontaneous locomotor activity experiment96male ICR mice, were randomly divided into8groups: Control (0.5%CMC-Na), JA (25,50,100mg/kg) group, JB (25,50,100mg/kg) group, Estazolam(1.5mg/kg) group. Continuous administration for3d record activities counts in5min, and then calculate inhibition rate. JB each dose could significantly reduce thespontaneous activities. JB50,100mg/kg could rise inhibition rate more than50%.JA each dose could not significantly reduce spontaneous activities.2.2Direct sleep experiment96male ICR mice, were randomly divided into8groups: Control (0.5%CMC-Na), JA (25,50,100mg/kg) group, JB (25,50,100mg/kg) group, Estazolam(1.5mg/kg) group. Put each mouse into a single cage immediately afteradministration, and record sleeping number and the time to fall asleep in3h.Sleeping was not found in JA, JB, indicating that JA, JB had no direct hypnoticeffect.2.3Experiment of sleep induced by subthreshold dose of pentobarbital sodium96male ICR mice, were randomly divided into8groups: Control (0.5%CMC-Na), JA (25,50,100mg/kg) group, JB (25,50,100mg/kg) group, Estazolam(1.5mg/kg) group. Continuous administration for3d, subthreshold dose (20mg/kg) of pentobarbital sodium was injected after administration in50min. Record sleepinglatency and sleeping number in30min to calculate the rate of sleep. JB each dosecould shorten sleep latency and increase sleeping rate significantly. JA each dosehad no significantly effect.2.4Experiment of sleep induced by threshold dose of pentobarbital sodium96male ICR mice, were randomly divided into8groups: Control (0.5%CMC-Na), JA (25,50,100mg/kg) group, JB (25,50,100mg/kg) group, Estazolam(1.5mg/kg) group. Continuous administration for3d, threshold dose (40mg/kg) ofpentobarbital sodium was injected after administration in50min. Recorded sleepinglatency and sleeping duration. JB each dose could shorten sleeping latencysignificantly but not prolong sleeping duration. JA each group has no significantlyeffect.3. Determination of neurotransmitters in the brains of mice60male ICR mice, were randomly divided into6groups: Control (0.5%CMC-Na), TFMP-85%(100,200mg/kg) group, JB (50,100mg/kg) group,Estazolam (0.5mg/kg) group. Continuous administration for3d,apply RIA andELISA for detecting. TFMP-85%and JB had a trend of increasing5-HT, GABA,decreasing NA, but no statistical significance. No significant effect of TFMP-85%and JB on5-HT, NA, DA,GABA was found.The results showed: TFMP-85%, TFMP-53%and JB had significant effects ofsedation hypnosis, JA had no significant sedation and hypnosis effects. TFMP-85%and JB had no significant effect on5-HT, NA, DA and GABA of normal mousebrain.In conclusion, TFMP-85%and JB have sedative and hypnotic effects, and needfurther development and utilization.