Pharmacological effects
Calming and hypnotic effects:
Suanzaoren water-soluble extract, equivalent to 7.5g crude drug per ml, dilute the stock solution to 1:1, 1:0.5, 1:0.25 in 3 concentrations, pH=9, and use 1.0ml per 20g.
1, the impact of the general activity of mice:
Direct observation test: Take 18.0±1.0g body weight of mice, each half, observe the normal activities before administration, and then give 1.0ml/20g ig of water extract with different concentrations of spinach.
Photoelectrical sedation test: Photoelectric sedators were composed of two light guides with crossed beams, and the number of spontaneous movements of mice within 10 minutes was recorded by a multiplier. The activity of mice in the 1:1 and 1:0.7 groups was significantly reduced.
Displacement test: Refer to Komlos et al. Shake-off drainage device for water discharge per unit time to indicate the activity of mice. The mice were divided into high-dose group (1:0.5), low-dose group (1:0.25), and control group. One ig administration, 30 minutes later began to observe the displacement within 15 and 30 minutes, 1:0.5 drug group compared to the control The drainage volume of the group was significantly reduced (P<0.01).
Shaking cage test: 18 ± 1.0 g mice were selected and randomly divided into two groups of 10 mice in each group. The administration group was treated with 1:1 jujubo kernel aqueous solution ig 1.0 ml/20 g body weight, and placed in shake cage after 30 minutes. Activity within 10 minutes. Results The spontaneous activity of the administration group was significantly reduced. Suanzaoren petroleum ether extract, n-butanol extract, ethyl acetate extract (the above extract is equivalent to 10 g of proto-drug per 1 ml) water decoction (concentration is 1 g equivalent to 1 ml of protoic drug), and the amount of pinosin is equivalent to 1 ml. Native drug 1mg. The shaking cage method was used for its own control experiment. The results are shown in Table 4. Except that the petroleum ether extract was ineffective, they all showed significant reduction in locomotor activity.
Reduce coordination movements: Select mice with a body weight of 18 ± 1.0g and turn for 1h on a rolling cage. Those who do not fall are eligible. Take 40, randomly divided into 4 groups according to gender of body weight, and give different doses of Suanzaoren water extract (equivalent to 7.5g of crude drug per 1ml, and diluted to 1:1, 1:0.5, 1:0.7) and physiological saline, with rolling The cage method was used for experiments. The rolling speed of the rolling basket was 6.5 wk/min. Ten mice were placed each time. After 30 minutes of ig administration, they were placed in a rolling cage and continued for 60 minutes. The number of animals dropped was observed. The results are shown in Table 5. The three concentrations all dropped more than 60%, and there was a very significant difference from the saline group.
2. Impact on animal sleep:
The effect of the water-soluble extract of Suanzaoren and pentobarbital sodium: Take 20 rats of 18.0±1.0g and randomly divide them into two groups according to body weight and gender. A group of water-soluble extract of Suanzaoren (approximately 7.5g of crude drug per ml, diluted to 1:1); the other group was given equal volume of normal saline as a control, 30 minutes after ig administration, each mouse ip 0.2% pentobar Sodium bromide 0.1ml/10g, once every 5 minutes to perform a righting reflex test until the disappearance of reflection disappeared within 30 minutes of record number, Suanzaoren water soluble extract can enhance the hypnotic effect of pentobarbital sodium. The water-soluble extract of Suanzaoren also significantly prolonged the sleep time of pentobarbital sodium in mice (P<0.05) but not chlorpromazine (P<0.01).
3. The effect of fried Zaoren decoction on sleep in rats: 18 Wistar rats weighing 160-240 g. They were randomly divided into experimental group and control group. They were placed in plexiglass cylinders and kept in isolation. Their activities were not limited. They were allowed to eat and drink freely and maintain natural light. Cortical electrodes were installed under pentobarbital anesthesia to record brain electricity. . Silver electrodes were inserted into the diaphragm and neck muscles of both sides to record myoelectricity and recorded continuously for 6 hours. Each rat was recorded 3 days before ig and 3 days after ig. Fry Zao Ren decoction is equivalent to 0.5g of original drug per 1ml. The experimental group used fried diarrhea decoction ig, 1ml each time, 2 times a day, and began to be administered from the night of recording d3 for a total of 3 days. The control group used the same amount of physiological saline. The sleep data analysis uses visual inspection, which takes a split time every 30 seconds. The sleep awakening cycle is divided into:
1) The awakening period is characterized by low amplitude fast wave brain electricity and obvious myoelectric activity guided by the frontal-parietal lobe;
2) Slow wave sleep (SWS) is characterized by a spindle wave (10-15 Hz) and a high amplitude slow wave (Q wave 0.5-5 Hz), during which myoelectric activity is significantly reduced. Among them, less than 50% of Q wave is slow wave sleep first phase (SWS1), which is equivalent to light sleep phase; Q wave is more than 50% is slow wave sleep second phase (SWS2), which is equivalent to deep sleep phase;
3) Paradoxical sleep (PS) is characterized by low amplitude fast waves (6-9H2) of the brain, with no obvious muscle activity except occasional muscle twitches;
4) The total sleep phase (TS) includes SWS1, SWS2, and PS. All experimental data were expressed as mean ± standard error (X ± SD, statistical analysis using the t test.
RESULTS: The duration of TS and SWS2 increased significantly in experimental rats after ig. Compared with before ig, TS duration increased by an average of 51.0 minutes (26.0%) within 6 hours, and average duration of SWS2 increased by 41.4 minutes (116.3%). The differences were very significant (P<0.001). There was no significant change in the duration of SWS1 and PS. There was no significant change before and after the control group ig normal saline. The frequency of seizure and duration of TS and SWS2 in the experimental group were significantly changed after ig. Compared with before ig, the frequency of TS seizures decreased by an average of 22.7 (-36.3%) within 6 hours, and the duration of each episode increased by 3.5 minutes (+95.6%); the average frequency of SWS2 seizures increased by 28.3 times within 6 hours (+89.O). %), all have very significant significance (P <0.001), while the duration of each attack of SWS2 prolonged 0.3 hours (+ 31.6%), there was a statistically significant (P <0.05). There was no significant change in seizure frequency and duration of seizure before and after the control group. In the experiment, it was also found that there were significant changes in the electroencephalogram patterns in most rats after ig, which was mainly manifested in the increase of high-amplitude slow waves during the slow-wave sleep stage. The amplitude increased and the frequency became slower, especially before ig. Rats are more pronounced. There was no significant change in the control group before and after ig.
Effect of Suanzaoren active ingredient on polysomnography in rats: Suanzaoren was degreased with petroleum ether and then extracted with water. Ammonium sulphate was added to a certain degree of saturation. Precipitates precipitated, dissolved in water, and insoluble substances were removed by filtration. After 3.O, cation exchange column chromatography was used. The column was washed with water until neutral, then eluted with NH4OH and fractionally collected in two portions, 1.90 g (SZ1) and 1.86 g (SZ2), respectively. Both SZ1 and SZ2 were formulated with physiological saline (NS) at 4g/L. In the 1h before the beginning of the tracing, 20 mg/kg body weight was used as ip. Rats were randomly divided into 3 groups, 11 in each group, respectively ip SZ1, SZ2, and NS, polysomnography, in order to avoid the effect of circadian rhythm on the experiment, the tracing was performed at the same time every day (2:00-6:00 pm). Each rat was continuously traced for 4 h before and after the administration, and the rats were treated by Usdin. The results were expressed as mean ± standard deviation (X ± SD) and statistically processed using a t-test. RESULTS: The total sleep time (TST) and slow wave sleep (SWS) increased significantly in the SZ1 and SZ2 groups, and the wakefulness (W) was significantly decreased. Compared with 1 h before administration, the TST increased by 21.7 ± 19.4 minutes (± 17.2%, P<0.001) and 27.7±18.5 minutes (+20.0%, P<0.001); SWS increased by 20.O±18.6 minutes (+17.0%, P<0.01) and 28.2±19.0 minutes, respectively ( (+21.9%, P<0.001), in which the slow sleep deep sleep period (SWS2) increased 8.4±12.1 minutes (+48.8%, P<0.005) and 25.3±19.4 minutes (+138.2%, P<0.01); W Respectively decreased 21.7 ± 19.4 minutes (-19.0%, P <0.01) and 27.7 ± 18.5 minutes (-27.3%, P <0.001), while slow wave sleep shallow sleep (SWS1) and fast wave sleep (PS) were There was no significant change. There was no significant change in each phase of the NS group before and after administration. From the time-effect relationship of active ingredients, the time-effect relationship between SZ1 and SZ2 was compared between hourly TST and SWS2 at the same time on the day of dosing. From the time when TST and SWS2 effects peaked after administration, SZ1 increased by 45.3% (P<0.01) and 186.7% (P<0.005) in h4-5 and TST and SWS, respectively, when the effect peaked, and SZ2 In the first 3-4 hours, TST and SWS2 increased by 23.6% (P<0.05) and 191.4% (P<0.01) when the effect peaked.
The role of anti-central stimulants:
Effect against pentylenetetrazol: Mice weighing 18±1.0 g were randomly divided into 3 groups. One set of water-soluble extract of spina date seed (1.0 ml/1 g equivalent to 7.5 g crude drug per 1 ml), divided into two igs, separated by 30 minutes, and administered with pentylenetetrazol half convulsions 50 mg after 30 minutes /kg, Observed after administration, the number of systemic convulsions and the mortality rate. Control saline. The results showed that the water-soluble extract of Suanzaoren had antagonistic effects on convulsions caused by pentylenetetrazol.
Against caffeine:
20 mice weighing 18.0±1.0 g were selected and randomly divided into two groups according to body weight and gender. One group was given a 1:1 water-soluble extract of Semen Ziziphinum (1.0 ml/20 g) (approximately 7.5 g crude drug per 1 ml, diluted to 1). : 1) In divided doses, 30 minutes apart, 30 minutes after the last dose, 50 mg/kg caffeine sodium benzoate. Control saline was used, and 50 mg/kg of sodium benzoate was given 30 minutes after the last administration and the activity curves of the mice in the two groups within 30 minutes were recorded by shaking cage. As a result, water-soluble extracts of spinach dated can reduce the tracings. The anticonvulsant effect of antipsychotics in mice showed that mice had no obvious antagonistic effect against 0.3ml/10g of ip Suanzaoren.
Effects on the cardiovascular system:
1. Effect of Suanzaoren on experimental arrhythmia
2. Effect of strontium chloride on arrhythmia in rats: Thirty-nine rats weighing 110-180 g, male or female, were divided into two groups, 20 in the Suanzaoren group and 19 in the control group. Ip 3% sodium pentobarbital 1ml/kg anesthesia, ip 10% chloral hydrate 2ml/kg 5 minutes later, using RM-46 type physiological recorder to observe and record lead I, II, III electrocardiogram. Then from the sublingual iv 0.4% guanidinium chloride solution 1ml/kg, within 5 seconds; after the occurrence of arrhythmia, the administration group from the sublingual iv above Suanzaoren solution 2ml/kg, the control group injected the same amount of physiology Saline, observe changes in ECG within 10 minutes. After injecting strontium chloride, arrhythmia waveforms mainly manifested in bipolar ventricular tachycardia appeared immediately in 39 rats. In the Suanzaoren group, the average sinus rhythm was converted to 20 seconds (14 within 10 seconds), and no arrhythmia waveform was observed after 10 minutes. There was no significant change in electrocardiogram after administration of saline to the control group, and the duration of arrhythmia was 1-10 minutes.
3. Effect of aconitine-induced arrhythmia in rats: 27 rats, weighing 110-220 g, 14 in the Suanzaoren group and 3 in the control group. Anesthesia with sodium pentobarbital (dose as above). The RM-46 physiological recorder was used to observe and record changes in the electrocardiogram. To 0.002% aconitine 1ml/kg sublingual iv, when the occurrence of arrhythmia, the administration group iv jujube kernel solution 2ml/kg, the control group iv the same amount of saline, observe and compare the two groups within 15 minutes of ECG changes. After aconitine injection, arrhythmia waveforms such as ventricular premature beats, ventricular tachycardia and other arrhythmias appeared within seconds to 4 minutes. Eight of the 14 rats in the Suanzaoren group had improved electrocardiographic waveforms (that is, they could recover sinus rhythm for several minutes, later appeared arrhythmia, recovered spontaneously in a short time, and thus repeated several times); and saline group 13 For rats, all arrhythmia waveforms persisted within 15 minutes. The two groups of results were directly calculated using the X2 test probability method, measured P <0.01, the difference is very significant.
4. Effect of Suanzaoren on myocardial ischemia induced by pituitrin in rats:
In the ip group: 18 rats weighing 160-220 g were divided into two groups of 9 in each group. After anesthesia, a group of pre-ip jujube kernel solution was 4 ml/kg (1 ml of crude drug 1 g), and the other group was administered with normal saline. . After 10 minutes, sublingual iv pituitrin injection 0.5u/kg, respectively, recorded with XDH-3 electrocardiograph at 1, 2, 15 and 30 seconds and 1, 2, 5, and 10 minutes after the injection of ECG II lead changes.
In the iv administration group, 10 rats were weighed 160-290 g and 5 in each group. After anesthesia, one set of iv prebiotics solution from the sublingual was 1.5 ml/kg, and the other was iv physiological saline. After 2 minutes, sublingual iv pituitrin was 0.75u/kg, and electrocardiogram changes were recorded at the same time as above. One person who had an electrocardiogram change in each of the following first and second phases was considered to have myocardial ischemia. Indications of myocardial ischemia: The first T wave is more than 50% higher than the original level, or the S-T segment is significantly down or pre-systolic. The second-stage ST segment was significantly down or the T-wave inversion was low and the heart rate was significantly slowed. The X-test directly calculated the probabilistic method to determine the difference of myocardial ischemia between ip and iv Suanzaoren and saline groups, the results are very significant (P <0.01).
The role of the heart:
Suanzaoren solution can reduce the heart rate of isolated and in vivo frog hearts, strengthen the heart contraction force, and have a strong heart effect.
The role of microcirculation:
Suanzaoren solution can significantly increase the diameter of microvascular vessels.
The effect of anti-anoxia on animals: 120 adult mice were randomly divided into hypoxic control group and Suanzaoren group according to body weight, 60 rats in each group. Decompression and hypoxia one day before the afternoon ig each mouse Suanzaoren decoction 0.4ml (containing crude drug 0.1g) hypoxia control group ig distilled water 0.4ml. Repeat ig twice every 2 hours before decompression hypoxia. The dose is the same as above. After the animal enters the decompression device, it is first decompressed to a simulated height of 3000m at a rapid speed (1000m/min), then slowed (200m/min) to 10,000m. After stopping for 1 hour, it returns to the plain height, and the animal survival rate is calculated. Results Twenty-seven mice survived in the control group and 48 in the medication group, P<0.01. Adult mice were used to observe the oxygen consumption of the simulated high-cerebral tissue. The results were compared between the drug group and the control group and the plain control group, P<0.05 and 0.01. After treatment significantly reduced the oxygen consumption of brain tissue.
Immunopotentiation:
Suanzaoren ethanol extracted brown extract significantly increased the lymphocyte transformation value of mice, and also significantly increased the production of mouse hemolysin in comparison with the control group. It can significantly enhance the phagocytic function of mononuclear macrophages in mice, and can significantly increase the small Rat delayed-type hypersensitivity can antagonize the inhibition of delayed hypersensitivity induced by CPA. Suanzaoren and polysaccharides were orally administered at a dose of 0.1 g/kg orally daily for 16 days to enhance the humoral and cellular immune functions of mice and to protect mice against radiation-induced injury.
Pharmaceutical toxicology
Toxicity: Suanzaoren 150g/kg was administered to the mice without toxicity. The chronic toxicity test showed that the toxicity of the rats was extremely low. The median lethal dose was 14.33±2.015g/kg. However, extremely high doses can also have toxic effects.
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