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Chinese Medicine can Improve Sleep
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Chinese Medicine can Improve Sleep
Frank Li Dec. 21 2011 Waterloo, Ontario, Canada
http://www.kwcg.ca/bbs/home.php?mod=space&uid=61910&do=blog&id=3851
The incidence of sleep disturbances are increasing with the increase of the intense of social competition. Insomnia, dreams, difficulty falling asleep and easy to wake up, those make the sufferers felt restless, upset，apathetic. It decreased the work efficiency and increased the cost on medication.
Modern researches have made clear that poor sleeping is not only affect the function of brain's memory and creative thinking, also can lead to lower immunity and induce diseases. Such as cancer, diabetes, arrhythmia, hypertension, kidney disease, cerebral vascular disease and mental problems, etc...
Synthetic sleep drugs are prone to drug-resistance, drug-addiction, extension effect, accumulation effect, withdrawal reaction and may cause serious negative consequences when long time use. Once the insomnia sufferer stop the use of synthetic sleeping drugs, will lead to further deterioration of insomnia. Also taking sleeping pills would impact work, study and social activities during the day time.
A report said that Sleep Drugs Found Only Mildly Effective, but Wildly Popular.
In Chinese, Chinese drugs has been used for treating sleep disorders for a long time. Modern pharmacological studies confirmed that besides sedative and hypnotic effect Chinese drugs can improve the sleep disorders in many aspects. Such as, regulate the central nervous system, improve the stress-related sleep disorders, promote the protein & DNA synthesis in brain, improve the learning & memory capability, increase the level of the pineal melatonin, maintain the brain dopamine levels, inhibit the apoptosis of dopamine neurons, etc. These effects are in favor of the treatment and prevention of sleep disorders.
Chinese drugs made of pure natural medicinal materials. The adverse effects are lesser; drug compliance is good, no drug dependence, no rebound insomnia and no iatrogenic disease. The prominent advantage is that Chinese sleep drugs can restore the overall health condition when impoving the sleeping disorders.
This article tries to demonstrate the unique therapeutic effect of Chinese drugs on improving the sleep.
1.1. Disturbed sleep associated with stress, anxiety and depression
1.2. Epidemiologic study of sleep disturbances & psychiatric disorders
1.3. The implications of sleep disturbance epidemiology
1.4. Are sleep disturbances risk factors for anxiety,depressive?
1.5. Effects of sleep deprivation on gastric mucosal blood flow and gastric mucosal lesions in rats
1.6. Sleep disturbances associated with minor psychiatric disorders
1.7．Stress Hormones and Insomnia
1.8.Dopamine Imbalances Cause Sleep Disorders
1.9.Dopamine is released with the individual anxious temperament
2. The treatment of sleep disorder
2.1. Synthetic drugs on sleep disorders
2.2. Effects of Chinese drugs on sleep disorders
2.2.1. Regulatory effect of Chinese drugs on central nervous system
2.2.2. Effects of Chinese drugs on stress-related sleep disorders
2.2.3. Effects of Chinese drugs on sleep Deprivation
2.2.3.1. Protective effects of eleutherosides on RN_8 acupoint application against sleep deprivation
2.2.3.2. The effect of nose drops Chinese drugs on sleep deprivation
2.2.3.3.Effects of ginsenosides on behaviors of rats in sleep deprivation
2.2.4. Chinese drugs on maintaining the dopamine levels
2.2.4.2. Influence of Yinxingpingchuan Formula on loss of DA neurons and apoptosis in mice with PD
2.2.5. Chinese drugs on sedative and hypnotic
2.2.5.1. The effect of Semen Ziziphi Spinosae on Sleep Improvement of Mice
2.2.5.2. Empirical studies of sedative and hypnotic effects of supplemented jujube seed granules
2.2.5.3. The Sedative and hypnotic effects of Jujuboside
2.2.6. Effect of Chinese sleep drugs integrating with synthetic sleep drugs
2.2.6.1. A controlled study of Tianmeng capsule combined with alprazolam in somnipathy
2.2.7. Effect of Chinese sleep drug on improving the learning ability
2.2.7.1. The effect of XinMeng Particles on learning process in rats
1. Some sleeping disorders related researches
1.1. Disturbed sleep associated with stress, anxiety and depression
A study of crossing the disciplines of psychology, medicine, neuroscience, and genetics reveals that stress causes deterioration in everything from your gums to your heart and can make you more susceptible to everything from the common cold to cancer.
“Sleep may be part of this puzzle too, as disturbed sleep, which often goes with anxiety and depression, increases levels of proinflammatory cytokines in the body.”
“Studies also have shown that optimistic people have lower incidence of heart disease, better prognosis after heart surgery, and longer life.”
1.2. Epidemiologic study of sleep disturbances and psychiatric disorders: an opportunity for prevention?
“Sleep disturbances have been linked to psychiatric illness, sleep apnea (arrested breathing while sleeping), emotional stress, cardiovascular disease, and even increased mortality. This study focused on the relationship between sleep disturbances and psychiatric disorders, because it was hypothesized that difficulty sleeping may be an early symptom of or conversely a cause of certain psychiatric illnesses. This investigation was part of the National Institute of Mental Health Epidemiologic Catchment Area study and it surveyed 7,954 people between 1981 and 1985. The respondents, adults from three US cities, were interviewed initially and then again after one year. Insomnia was found in 10.2 percent of the respondents and hypersomnia in 3.2 percent at the first interview. Of the people with either insomnia or hypersomnia, 40-47 percent had a psychiatric illness as well while only 16.4 percent of people with no sleep complaints had a psychiatric problem. Specifically, the chance of developing a new major depression was much greater for insomniacs than respondents without insomnia. If sleep problems had resolved by the second interview, new psychiatric illness was less likely to develop. The authors suggest that physicians could possibly prevent new or recurrent psychiatric disorders by diagnosing and addressing sleep complaints promptly.”
1.3. The implications of sleep disturbance epidemiology
“The author reviews an article by Daniel Ford and Douglas Kamerow, "Epidemiologic study of sleep disturbances and psychiatric disorders", in the Sep 15, 1989 issues of The Journal of the American Medical Assoc. and finds it to be an exceptionally well-designed and meaningful project. The high rate of psychiatric illness discovered in patients with hypersomnia (excessive daytime sleepiness) is surprising. This is the first evidence that psychiatric illnesses such as depression occurs in many unusually sleepy patients. The finding that many insomniacs (those who have difficulty sleeping) had psychiatric disorders confirms previous results but also adds useful data on the course of these problems over time. Most fascinating is the suggestion that early diagnosis and management of sleep disorders could prevent psychiatric illness. This concept is compatible with the theory that changes in sleep patterns may occur before psychiatric problems such as depression develop. The reviewer proposes strategies for early clinical intervention to treat sleep disorders. Patients should wake up at the same time every day and avoid using stimulants or depressants. Modest restriction of time spent in bed to 6 or 7 hours may help some patients with insomnia sleep more deeply and steadily. Mental illness is not the only cause of insomnia, however. Social changes such as unemployment or death of a family member, or physical pain and disability also frequently affect sleep.”
1.4. Are sleep disturbances risk factors for anxiety, depressive and addictive disorders?
“More tentatively, preliminary data suggest that increasing subjective sleep disturbance may signal a relapse in remitted depressed patients. Sleep disturbances are common manifestations of major depressive and anxiety disorders. Therefore, sleep complaints may be among the most robust prodromal symptoms reflecting partial depressive or anxiety disorders, which eventually declare themselves as full-blown clinical episodes.”
1.5. Effects of sleep deprivation on gastric mucosal blood flow and gastric mucosal lesions in rats
METHODS: Sleep deprivation was induced in male Sprague-Dawley rats housed on small platform over water. Control mice were housed either in normal cages or on large platform over water. Laser Doppler blood flow meter was used to measure the gastric mucosal blood flow, and index of gastric mucosal lesions was quantified. The arterial plasma levels of endotoxin (ET) and calcitonin gene related peptide (CGRP) were measured by radioimmunoassay.
RESULTS: Compared with control mice in normal cage, on big platform, or the mice on the 1st day of sleep deprivation, the gastric mucosal blood flow of mice on the 3rd, 5th and 7th day of sleep deprivation (54.2±2.5, 53.7±3.0, 48.3±2.5 mv, respectively) were significantly lower. The gastric mucosal injury became more and more serious: the injury indices were 29.8±3.2 , 3.7±3.6 and 34.8±3.5 on the 3rd, 5th and 7th day of sleep deprivation, respectively. The serum levels of ET were 123±28, 139±36 and 149±38 ng/L in mice on the 3rd, 5th and 7th day of sleep deprivation, and the levels of CGRP were 193±32 and 221±40 ng/L in the mice on the 5th and 7th day of sleep deprivation. All were significantly higher than those in control mice.
CONCLUSION: Sleep deprivation can cause the decrease of gastric mucosal blood flow and the gastric mucosal injury, which are accompanied by the elevation of serum ET and CGRP.
1.6. Sleep disturbances associated with minor psychiatric disorders in medical students
“We performed a cross-sectional study with 342 medical students (age range, 18–35 years) to identify, among a group of sleep disturbances, those which are related to minor psychiatric disorders in this population. The instruments employed for data collection were the self-reporting questionnaire (SRQ-20), the morningness/eveningness questionnaire, the Epworth sleepiness scale, and a general questionnaire regarding demographic characteristics, use of drugs, history of psychopathology, usual fall-asleep time, usual wake-up time, amount of sleep, arousal during the night, and insomnia. We used a logistic regression model to determine independent factors associated with minor psychiatry disorders. Daytime sleepiness [odds ratio (OR), 2.12; 95% CI, 1.21–3.71], arousal [OR, 4.54; 95% CI, 1.97–10.47], insomnia [OR 2.45; 95% CI, 1.32–4.56], and sleeping less than 7 hours per night [OR, 2.02; 95% CI, 1.11–3.67] were associated with minor psychiatric disorders. This group of variables determined a cumulative risk ratio of 5.47 [95% CI, 2.87–10.41] for the main outcome.”
1.7．Stress Hormones and Insomnia
"The increased prevalence of insomnia in middle-age may, in fact, be the result of deteriorating sleep mechanisms associated with increased sensitivity to arousal-producing stress hormones, such as CRH and cortisol," Vgontzas and colleagues suggest.”
“In another study, the researchers compared patients with insomnia to those without sleep disturbances. They found that "insomniacs with the highest degree of sleep disturbance secreted the highest amount of cortisol, particularly in the evening and nighttime hours," suggesting that chronic insomnia is a disorder of sustained hyperarousal of the body's stress response system.”
1.8. Dopamine Imbalances Cause Sleep Disorders In Animal Models Of Parkinson's Disease And Schizophrenia
“Neuroscientists at Duke University Medical Center working with genetically engineered mice have found that the brain chemical dopamine plays a critical role in regulating sleep and brain activity associated with dreaming.”
“When dopamine levels were dramatically reduced, the mice could no longer sleep, the scientists said. When dopamine levels were increased, the mice exhibited brain activity associated with dreaming during wakefulness.”
“The same processes likely occur in humans, according to the researchers. They said the findings give insight into the sleep problems common among patients suffering from Parkinson's disease, a neurodegenerative disorder in which brain cells containing dopamine die or become impaired.”
1.9．Dopamine is released with the individual anxious temperament
“Dopamine is released under stress and modulates processing of aversive stimuli. We found that dopamine storage capacity in human amygdala, measured with 6-[(18)F] fluoro-L-DOPA positron emission tomography, was positively correlated with functional magnetic resonance imaging blood oxygen level-dependent signal changes in amygdala and dorsal anterior cingulate cortex that were evoked by aversive stimuli. Furthermore, functional connectivity between these two regions was inversely related to trait anxiety. Our results suggest that individual dopamine storage capacity in amygdala subserves modulation of emotional processing in amygdala and dorsal cingulate, thereby contributing to individual differences in anxious temperament.”
Lack Of Sleep Linked To Increased Cancer Risk
Lack of sleep and confusion in the diet doubling the young people of gastric cancer
Lack of Sleep Greatly Increases Breast Cancer Risk
Poor sleeping raises risk of high blood pressure
2. The treatment of sleep disorder
Above findings showed that sleep disturbances are related with various factors, especially the psychological stress and dopamine level. So that treatment should focus at a variety of factors comprehensively. After improving the overall health condition, the sleeping would be restored to normal naturally.
2.1. Synthetic drugs on sleep disorders
At present, the sleeping drugs are mainly synthetic drugs in sedative and hypnotic. At the time they take the effect on improving sleep disorders, also bringing the negative effects. Such as, prone to drug-resistance, drug-addiction, extension effect, accumulation effect, withdrawal reaction and may cause serious negative consequences when long time use. Once the insomnia sufferer stop the use of Western sleeping drugs, will lead to further deterioration of insomnia. Also taking sleeping pills would impact work, study and social activities during the day time.
Then, how much positive effects that patients can enjoy during suffering the harmful negative effects? A report said that Sleep Drugs Found Only Mildly Effective, but Wildly Popular.
"The analysis said that viewed as a group, the pills reduced the average time to go to sleep 12.8 minutes compared with fake pills, and increased total sleep time 11.4 minutes. The drug makers point to individual studies with better results."
"Subjects who took older drugs like Halcion and Restoril fell asleep 10 minutes faster and slept 32 minutes longer than the placebo group. Paradoxically, when subjects were asked how well they slept, they reported better results, 52 extra minutes of sleep with the older drugs and 32 minutes with the newer drugs."
"Rozerem, consider that it costs about $3.50 a pill; gets you to sleep 7 to 16 minutes faster than a placebo, or fake pill; and increases total sleep time 11 to 19 minutes, according to an analysis last year."
"American consumers spend $4.5 billion a year for sleep medications." “Sleep Drugs May Not Help Much.”
2.2. Effects of Chinese drugs on sleep disorders
Usually the anxiety, panic, depression and forgetfulness are often associated with sleep disorders at the same time. Therefore, in ancient China, the forgetfulness, panic and severepalpitation are often mentioned in the same breath with the treatment of Sleep Disorders.
Some Chinese drugs preparations can regulate not only the sleep, but also can effectively prevent and treat depression, anxiety, panic and other psychological disorder at the same time.
In the patients with depression, some wake up earliy, some sleep time decreased while others sleep too much. It was found that treatment using the same prescription of Chinese drugs is effective not only for the insomnia but also effective for excessive sleep. The facts show that the Chinese drugs can regulate the sleep disorders in bidirectional way wisely.
Modern pharmacological studies confirmed that besides sedative effect, some Chinese drugs can promote the function of learning and memory.
Chinese drugs made of pure natural medicinal materials. The adverse effects are lesser, drug compliance is good, no drug dependence, no rebound insomnia and no iatrogenic disease. The prominent advantage is that Chinese sleep drugs can restore the overall health condition when impoving the sleeping disorders.
2.2.1. Regulatory effect of Chinese drugs on central nervous system
Animal experiments have showed that Chinese drugs possess the dual role of excitement and inhibition for central nervous system. It can increase the excitement process of cerebral cortex, but also to strengthen the inhibition process of central nervous system, so that the excitement and inhibition achieve balance.
Chinese drugs can reduce the animal heart rate, reduce adrenaline output in urine, decrease the activity of dopamine p hydroxylase (DBH) that participate the synthesis of catecholamine, reduce the output of endocrine 17 OHCS in urine, decrease the oxygen consumption, so that lower the excitatory of adrenal sympathetic nerve.
2.2.2. Effects of Chinese drugs on stress-related sleep disorders
Better Sleep Council Survey Shows 51 Percent of Americans Are Losing Sleep over Stress.
Researchers at Pennsylvania State University College of Medicine have found that reason why middle-aged men may be losing sleep. It's not just because of what they worry about. Rather, it's due to "increased vulnerability of sleep to stress hormones."
Researchers compared patients with insomnia to those without sleep disturbances. They found that "insomniacs with the highest degree of sleep disturbance secreted the highest amount of cortisol , particularly in the evening and nighttime hours," suggesting that chronic insomnia is a disorder of sustained hyperarousal of the body's stress response system.
In as much as stress is the incentive for sleep disturbance, then mitigates the harm of stress on the prevention of sleep problems have great significance.
Stress is the result of comprehensive reaction of the body against the social pressure. Due to the social factors are often unexpectable and uncontrollable, therefore, that the enhancement of the physical ability against stress will be a feasible approach in the prevention and treatment of stress-related sleep disorders.
Many studies show that Chinese drugs can relieve the negative effects of psychological stress through releasing endorphins, decreases the stress hormone cortisol, lowers blood pressure, reduces heart rate, relaxes muscle tissue, and bring more fresh oxygen to body tissues by improving the circulation of blood and lymphatic fluids. This increased oxygen flow will eliminate waste products from inside the body and enhance the recovery from situation being impaired. Those therapeutic effects will improve the sleep disorders.
2.2.3. Effects of Chinese drugs on sleep deprivation
2.2.3.1. Protective effects of eleutherosides on RN_8 acupoint application against sleep deprivation
Methods: 24 young healthy volunteers (males, 19～22 years old) were randomly divided into four groups: Normal control group (NC), sleep deprivation group (SD), treated control group (TC), and placebo control group (PC). Sleep deprivation in volunteers of SD, PC and TC groups were conducted for 48 hours. Eleuthersides were applied to RN8 acupoint of TC group volunteers and placebo on that of PC group. Serum cortisol (Cor) and testosterone (T) were detected, at the same time, the psychology questionnaire of Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS) were evaluated to observe the influence of SD and the protective effects of eleuthersides acupoint application.
Results: After 48h SD, the mean increase of serum Cor level of TC (16.117±34.807 ng/dl) was lower than that of BC (53.192±25.752 ng/dl) (P<0.05), the mean increase of SDS score (2.833±16.746) was also lower than that of BC (20.417±10.358) (P<0.05), but no obvious different was found between BC and TC in change of the serum T level and SAS standard score (P>0.05).
Conclusion: Eleuthersides acupoint application affects person with sleep deprivation by regulation of stress response and psychological function.
2.2.3.2. The effect of nose drops Chinese drugs on sleep deprivation
Methods: By 72h rapid eye movement with flower pot technique, establish rat’s sleep deprivation model. Nasal drops Chinese drugs for the treatment group.
Results: in the groups of high, medium and low-dose Chinese drugs, for the count of the times of rats’ falling into water, there was a significant difference with the control group. The test of learning, memory and motor function, in the groups of high, medium dose Chinese drugs were significantly different than the control group.
Conclusion: The nasal drops of Chinese drugs can take the effect of anti-sleep deprivation by improving the degree of fatigue, the ability of learning and memory and the coordination of movement.
2.2.3.3.Effects of ginsenosides on behavior of rats in sleep deprivation
Methods: by flower pot technique, 24 male Sprague-Dawlay rats were divided into three groups randomly. 24 SD (being deprived of sleep for 24 hours), 48 SD (being deprived of sleep for 48 hours), 72 SD (being deprived of sleep for 72 hours) , and every group was also divided into two subgroups: experimental group and control group. Ginsenosides were forced fed to the experimental groups continuously for 5 days, and normal saline to the controls, then the rats were being deprived of sleep for different times. Before and after SD immediately, the behaviors of rats were studied in ”Y” maze test and open-field test.
Results: ①“Y” maze test: Compared with control groups, the accuracy of the reaction of experimental groups increased significantly in 24 SD, 48 SD and 72 SD (P<0.05), and the time of electrification decreased markedly (P<0.05). The difference enhanced with the increase of SD times, and reached to the highest in 72 SD (P<0.01). ② Open-field test: Compared with the control groups, the time of staying in center and the rearing of experimental groups increased significantly in 72 SD (P<0.05), and there was no obvious difference between 24 SD and 48 SD (P>0.05), the Crossing of experimental groups increased significantly in 48 SD and 72 SD (P<0.05), and there were no obvious difference in 24 SD (P>0.05).
Conclusion: GS can improve the disorder of learning, memory and activity of rats induced by SD, and the effect may enhance with the increase of SD time to a certain extent.
2.2.3.4. Effect of An-shen-bu-nao (Compound Chinese drugs) syrup on learning, memory and BDNF expression in hippocampus of sleep deprivation rats
METHODS: 75 rats were divided into groups of An-shen-bu-nao syrup treatment groups and distillated water control groups. All rats were fed with 2 weeks, and they were subjected to sleep deprivation for 4 days.
Results: The latency of passive avoidance was significantly reduced in rats of sleep deprivation. Large-dose An-shen-bu-nao syrup can significantly increase the rats’ latency of passive avoidance. Chinese drugs can also extend the latency of passive avoidance for normal rats. In the rat’s hippocampus area of sleep deprivation there is a significant reduction in the expression of Brain-derived neurotrophic factor (BDNF). Chinese drugs can increase the expression of BDNF obviously.
Conclusion: An-shen-bu-nao syrup can effectively reduce the impairment in rats learning and memory induced by sleep deprivation. The one of mechanism may be the enhancement of the expression of BDNF in the rat’s hippocampus area.
2.2.3.5. Effect of An-shen-bu-nao (Compound Chinese drugs) Syrup on Learning and Memory Capability and Protein Synthesis in Brain of Mice
Methods: The learning and memory capability of mice was investigated by Y-water maze test and step-down test. The contents of protein, DNA and RNA were investigated by Lowry methods, the diphenylamine reagent method and Oricinol reagent method.
Result & Conclusion: An-shen-bu-nao (Compound Chinese drugs) Syrup could enhance the memory capability of normal mice and improve the memory emersion disorder of mice induced by ethanol. In addition, it could significantly increase the content of protein, DNA in mouse brain.
Methods: Rats were divided into normal group, control group and treatment groups. The rats were fed with Chinese drugs for 2 weeks and were subjected to sleep deprivation for 4 days, and then the iNOS activity in the front cortex was analyzed, and the melatonin content in the pineal gland was analyzed with HPLC.
Results: Compared with the normal group, in sleep deprivation group, the activity of iNOS increased significantly, pineal melatonin is on a decreasing trend. In large dose of An-Shen-Bu-Nao Syrup group, the activity of iNOS significantly decreased and the content of pineal melatonin significantly increased.
Conclusion: An-Shen-Bu-Nao Syrup could antagonize the vitality of the rats’ brain iNOS and increase the level of the pineal melatonin for the sleep deprivation rts. Indicates that Chinese drugs can improve the changes in brain function caused by sleep Disorders.
2.2.4. Chinese drugs on maintaining dopamine levels
Research shows that dopamine imbalances cause sleep disorders. In mice model, the brain chemical dopamine plays a critical role in regulating sleep and brain activity associated with dreaming. When dopamine levels were dramatically reduced, the mice could no longer sleep. When dopamine levels were increased, the mice exhibited brain activity associated with dreaming during wakefulness.
The same processes likely occur in humans, according to the researchers. They said the findings give insight into the sleep problems common among patients suffering from Parkinson's disease, a neurodegenerative disorder in which brain cells containing dopamine die or become impaired.
Therefore, it is very important that maintains the dopamine in normal levels.
2.2.4.1.Protective effects of the serum with Chanfuning decoction on mesencephalic dopaminergic neurons in vitro and its mechanism
Methods: Chanfuning serum made of Chinese medicine by Serum pharmacologic method. 100?mol/L 6-OHDA and Chanfuning serum were added into the medium of dopaminergic neurons. The tyrosine hydroxylase (TH) immunocytochemistry staining and automatic image analysis were applied to investigate the numbers, the length of the longest neurite and soma area of dopaminergic neurons; The concentrations of the intracellar Ca(superscript 2+) was detected with laser scanning confocal microscope.
Results: After damaged by 6-OHDA, the number of surviving TH-positive cells in Chanfuning serum treated group increased significantly than in control serum group; The mean longest neurite length of TH-positive neurons exposed to the medium with Chanfuning serum was significantly longer than that of TH-positive cells in the control serum cultures. There was no significant difference in the cell soma area. The concentrations of intracellar Ca(superscript 2+) in cells treated by Chanfuning serum significantly decreased than that of the cells treated by control serum.
Conclusions: Chanfuning serum may have direct nutrition effects on dopaminergic neurons and protect them from injury induced by 6-OHDA.
2.2.4.2. Influence of Yinxingpingchuan Formula on loss of DA neurons and apoptosis in mice with PD
Yinxingpingchuan Formula is a compound Chinese drugs recipe.
Methods: To establish the mouse model of Parkinson's disease (PD) by intraperitoneal injection of MPTP. Immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) technique were used to observe the influence of Chinese herbal drugs on the loss of (mesencephalic) nigra dopamine (DA) neurons and apoptosis.
Results: In the model group the positive neurons of tyrosine hydroxylase (TH) in mouse nigra compact part decreased obviously than that of the normal group,which was more obvious on 14th day than on 28th day. Yinxingpingchuan Formula and its decompositions could reduce partially the loss of TH positive neurons in mesencephalic nigra compact part.In the model group the apoptosis cells in mouse mesencephalon increased obviously, which was more obvious on 14th day than on 28th day. In the different groups treated with Chinese herbal drugs the apoptosis was inhibited at different degrees.
Conclusion: Cells apoptosis may be one of the common styles of dopamine neuron loss in mesencephalon of mice with Parkinson's disease. Yinxingpingchuan Formula can prevent and treat Parkinson's disease by inhibiting the apoptosis of cells and reducing the loss of the dopamine neuron.
2.2.4.3. Effects of Yijingyangxue Prescription on Apoptosis of the Dopaminergic Neurons in Rats with Parkinson Disease (PD)
Yijingyangxue Prescription (YP) is a compound Chinese drugs formula.
Methods: PD models were established by microinjection of 6-hydroxydopamine (6-OHDA) into the substantia nigra of the right side of the brain. The model group, experimental (YP) group and the normal group were set up. The model and normal group rats were given normal saline and the experimental group rats were given YP by gastric gavage for 30 days. Rotational behavior of rats was examined. The expressions of TH, Bcl-2 and Caspase-3 in the substantia nigra were detected using immuohistochemical method. Ultrastructural changes of dopaminergic neurons in the pars compacta of the substantia nigra (SNc) were observed.
Results: The experimental group rats showed less rotational behavior after therapy (P<0.05). The survival percentage (6-OHDA) injected side in comparison with mormal side) of the number of TH immunoreactive cells in the SNc of experimental group rats was higher than that of he model group (P<0.05). The OD value of Caspase-3 in the SNc of 6-OHDA injected sides obviously decreased in the experimental group compared with the model group (P<0.05). The changes of Bcl-2 were opposite to those of Caspase-3. Under immunoelectronic microscopy, TH immunoreactive products were located on the membrane of Golgi apparatus and cytoplasm of TH positive cells, and their electron density was condensed, TH immunoreactive products were found in the normal group, less in the experimental group, but least in the model group. And the ultrapathological changes in the experimental group were less than those of the model group,
Conclusion: Yijingyangxue prescription could obviously inhibit the apoptosis of dopaminergic neurons in the SNc of PD rats.
2.2.4.4. Neuroprotective Effects of Ginsenoside Rg1 on the Dopaminergic Neurons in the Substantia Nigrain Mptp-Treated C57BL6 Mice
Method: Mice were randomly divided into three groups: Control group (NS, ip), MPTP group (30mg/kg×5d, ip) and Rgl (5mg/kg×8d, ip) pretreatment group. Using RT-PCR, tyrosine hydroxylase (TH) immunohistochcmistry and HPLC, the degeneration of dopaminergic neurons was measured in the SN of MPTP treated mice and assessed the effects of treatment with ginsenoside Rgt.
Results: The number of TH-immunoreactive cells in the SN of MPTP treated mice, as well as the contents of dopamine and its metabolites in the striatum, decreased significantly. Treatment with ginscnoside RgI reversed these effects (P<0.01). The expression of Bcl-2 and TH mRNA in the SN also decreased significantly in MPTP treated mice (P <0.01), while the expression of Caspase-3 and Bax mRNA increased significantly (P<0.01). Treatment with ginsenoside Rgl reversed the above changes (P<0.05).
Conclusion: Ginsenoside Rgl has obvious protective effect on SNDA neurons of the mouse with MPTP-induced Parkinson's disease. The mechanism is possibly due to its anti-apoptosis activity.
2.2.4.5. Protective effect of Plastrum Testudinis on the apoptosis of dopamine neurons of rats with Parkinson's disease
Methods：6 - hydroxydopamine (6-OHDA, 0.2%) injection cause rats Parkinson’s disease (PD) model. Treatment group administered Chinese drug preparation of turtle shell for 12 weeks.
Results: In Chinese drug group, the improvement of rat’s rotational behavior is significant. TH-stained positive neurons increased in the area of substantia nigra. DIG-dUTP stained positive rate decreased. Bel-2 protein expression increased and Bax protein expression decreased.
Conclusion: Chinese drug has an obvious protective effect for dopaminergic neuronal apoptosis of PD model rats.
2.2.5. Chinese drugs on sedative and hypnotic
China, 1994-2007 domestic journals have published 233 cases of Chinese drugs prescriptions that used to treat insomnia, among them there are 52 prescriptions with a random distribution and the control group. In above 52 prescriptions, the top frequently used Chinese drug is the Semen Ziziphi Spinosae (or called jujube seed). Here I will take the Semen Ziziphi Spinosae (jujube seed) as an example to demonstrate the therapeutic effect of Chinese drugs on sleep.
2.2.5.1.The effect of Semen Ziziphi Spinosae on Sleep Improvement of Mice
Method: 58 male ICR mice, body weight (22 ± 2) g. randomly divided into 4 groups. 16 mice in each treatment group of gastric feeding powder of Semen Ziziphi Spinosae (SZS) in three dosages (570 mg/kg,1000 mg/kg and 2000 mg/kg), 10 mice in each control group of distilled water. Determine the indicators after feeding 30 d.
The experiment of extending the sleep time induced by pentobarbital sodium. After 30 d feeding and 20 min of last feeding, intraperitoneal injection of 50 mg / kg pentobarbital sodium each group of mice. Take the disappearance of righting reflex as an index to observe the sleep time.
The content of 5-HT in the brain of mouse was measured by fluorescence assay.
Results: Direct sleep test: After 60 min administration of powder preparation, all groups mice have no sleep occurred and the activities as normal.
The test of extending the sleep time of pentobarbital sodium: Low-dose and medium dose powder of Semen Ziziphi Spinosae can significantly extend the sleep time in mice, compared with the control group, the differences is significant (P<0.05)，high-dose group is no significant differences (P>0.05).
Subliminal hypnosis dose experiments of pentobarbital sodium: Middle dose and high dose groups’ mice were significantly increased in the sleep rate of 30 min compared with the control group, the differences are significant (P<0.05). Low-dose group had no significant difference (P >0.05).
The determination of 5-HT in mice brain tissue: Compared with the control group, the 5-HT content was significantly increased in low-dose group (P>0.05). Middle dose and high dose group had no significant difference (P>0.05). Low dose of Semen Ziziphi Spinosae powder can significantly extend the sleep time induced by pentobarbital sodium and improve the content of 5-HT in mice brain (P<0.05).
Conclusion: Semen Ziziphi Spinosae has the effect of improving the sleep but no obviously direct hypnotic effect and the sleep improvement is relevant with the dose and 5-HT content of mouse brain.
2.2.5.2. Empirical studies of sedative and hypnotic effects of supplemented jujube seed (SJS) granules
SJS is a compound of Semen Ziziphi Spinosae with other Chinese drugs.
Method: 60 mice, half male and female, were randomly divided into 5 groups of 12 mice. Control group given normal saline. Treatment group gastric gavage SJS for 7 days in low dose 2.21 g·kg-1，middle dose 4.42 g·kg-1 and high dose 8.84 g·kg-1 separately. 1 h after the last administration, the mice were put into the activity box by group and let them adapt to 5 min, and then record the number of activities of the mice in each group every 15 min for analysis.
The effct of SJS on sleeping time of latency and duration in mice induced by pentobarbital sodium
50 mice, half male and female, were randomly divided into 5 groups of 10 mice. Treatment group gastric gavage SJS for 7 days in low dose 2.21 g·kg-1，middle dose 4.42 g·kg-1 and high dose 8.84 g·kg-1 separately. 1 h after the last administration, intraperitoneal injects pentobarbital sodium for each mouse. From the disappearance of righting reflex to the resumption of righting reflex in mice as sleep duration, Record the sleep latency and duration of sleep time for each mouse.
Results: Compared with the control group, the spontaneous activities of mice was significantly reduced in the groups of middle and high dose SJS. The difference was significant or very significant (P<0.05 or 0.01).
The effct of SJS on the time of sleep latency and duration induced by pentobarbital sodium
Compared with the control group, the time of sleep latency was significantly reduced in the group of middle and high dose SJS, the difference was significant or very significant (P<0.05 or o.o1). The time of sleep duration was significantly increased, in the group of middle and high dose SJS, the difference was significant or very significant (P<0.05 or o.o1), too.
Conclusion: SJS has obvious sedation and hypnotic effects.
2.2.5.3. The Sedative and hypnotic effects of Jujuboside
Methods: By the method of transducer cage shake, tilted glass plate and righting reflex to determine the effect of Jujuboside on coordination of movement, sedation and hypnotic for normal mice and normal rats.
Results: For normal mice, the high, medium and low dose Jujuboside could reduce the the number of activities, inhibit the central excitatory effect of amphetamine, reduce the ability of the coordination of movement, significantly increase the number of mice to fall asleep and the time of sleep of threshold dose of pentobarbital sodium.
Conclusion: jujuboside has pronounced effects of sedative and hypnotic.
2.2.5.4. Effects of the Seeds of Ziziphus spinosa Hu (Semen Ziziphi Spinosae) on the lmmune Function of Mice
“This article surveys the effects of alcoholic extract of Ziziphus spinosa on the immune function of mice. It was found that oral dosing of the seeds of Ziziphus spinosa (5g/kg. d×20) increased the appetite and weight of mice and strengthened the immune function of their cells and body fluid. The delayed hypersensitivity induced by cyclophosphamide was inhibited in the group administered with Ziziphus spinosa. The result suggests that the seeds of Ziziphus spinosa can improve the immune function of mice.”
2.2.6. Effects of Chinese drugs integrating with synthetic sleep drugs
Chinese drugs integrating with synthetic sleep drugs can take the synergy effect in enhancing the positive effect and reduce the negative effects for each other.
2.2.6.1. A controlled study of Tianmeng capsule combined with alprazolam in somnipathy
Tianmeng capsule is a compound Chinese drug for treating sleep disorders.
Objective: To explore the therapeutic effectiveness and side effects of Tianmeng capsule combined with alprazolam in somnipathy.
Methods: 84 patients with somnipathy were divided into 2 groups (both n=42) according time order. Research group took Tianmeng capsule combined with alprazolam and control group did single alprazolam for 4 weeks. Clinical effectiveness and side effects were assessed with the Pittsburgh Sleep Quality Index and Self made Treatment Emergent Symptom Scale before treatment and at the ends of 1st，2nd and 4th week during treatment and at the ends of 1st，4th and 8th week after treatment，respectively. 65 patients of both the 2 groups completed treatment and follow up.
Results: After 4 week treatment，sleep quality of the patients improved. Compared with the control group，the mean dosage of alprazolam was smaller in the research group，side effects were fewer and milder and duration of sleep improvement longer after treatment.
Conclusion: Tianmeng capsule combined with alprazolam had precise curative effect in somnipathy, dose was smaller and side effects were fewer and milder, and rebound phenomenon was not marked after treatment.
2.2.7. Effect of Chinese sleep drug on learning ability
2.2.7.1. The effect of XinMeng particles on learning process in rats
XinMeng particle is a compound Chinese drug (containing Jujuboside 10.3mg and total flavonoids 19.49mg /100g) for treating insomnia. It is very good on improving the sleep disorder. Studies show it can improve the learning capacity, too.
Method: Mice Y maze test, XinMeng groups in dose of 21.5 g/kg, 43.0 g/kg and 86.0 g/kg separately administrated for 7 days.
Results: Compared with the control group, the times of total training in learning process was significantly reduced in the group of 86.0 g/kg (P<0.05). Other dose group can not significantly reduce the times of total training (P>0.05). However, 43.0 g/kg group clearly shows against access barriers of learning induced by scopolamine (P<0.01).
Conclusion: XinMeng has a certain effect on the promotion of the learning process, and can inhibit the learning dysfunction induced by Scopolamine.
