Directions: mix 1/4 – 1/2 tsp in warm water, grapefruit juice or chamomile tea one hour before bed for ultra high quality sleep. Wake up the next morning feeling INCREDIBLE! Zero grogginess!
DEEP REJUVENATIVE SLEEP—ABSOLUTELY CRITICAL to LONGEVITY!
*For best results avoid, coffee, tea, caffeine and any other stimulants at least 4 hours before bed especially if insomnia is an issue.
Objective:To study the sedative and hypnotic effect of Acanthopanax senticosus combined with Schisandra chinensis in mice.Methods:Study the dose-effect relationship on Acanthopanax senticosus and Schisandra chinensis in the effect of improving sleep.By inducing dormancy of the mice with subliminal and suprathreshold dose of sodium pentobarbital adding the herbs to evaluate the sedative and hypnotic effect of these two herbs used alone or together.Results:The best dose of Acanthopanax senticosus(16~128g/kg)which prolonged the time of falling asleep(P0.01)in mice was 64g/kg.The best dose of Acanthopanax senticosus(3~12g/kg)which shortened the duration sleep latency(P0.05)in mice was 12g/kg.Contrasting to the blank group,Acanthopanax senticosus combined with Schisandra chinensis could reduce the latent period of falling asleep(P0.01),prolong the sleep time induced by sodium pentobabital(in suprathreshold dose)(P0.01),and remarkedly enhance the rate of falling asleep induced by sodium pentobabital(in subthreshold dose)(P0.05).Its effect is superior to the effect of Acanthopanax senticosus or Schisandra chinensis.Conclution:Acanthopanax senticosus combined with Schisandra chinensis had obvious effects on the sedation and hypnosis of mice.
Asperugo procumbents L. has been used in Iranian traditional medicine for the refreshing, tranquillizing and mood elevating activities. The present study was undertaken to evaluate the antidepressant and sedative–hypnotic potential of acute administration of the hydroalcoholic extract of this plant in mice. Additionally, the effects of flumazenil on the hypnotic activity of the extracts were evaluated. None of the doses of the extract could significantly reduce immobility time in comparison with control group in antidepressant tests. In hypnotic test, 250 and 400 mg/kg doses significantly increased pentobarbital-induced sleeping time compared to vehicle. All of the doses of the extract significantly reduced the latency to sleep in comparison to the vehicle. Flumazenil reversed the augmented effects of extracts in pentobarbital-induced hypnotic test. The results of the present study indicate the low antidepressant and good sedative–hypnotic effects of the hydroalcoholic extract of Asperugo procumbens aerial parts in mice and that the central benzodiazepine receptors are involved in the sedative–hypnotic effects of this plant.
Byrsonima crassifolia (Malpighiaceae) has been used in traditional medicine for the treatment of some mental-related diseases; however, its specific neuropharmacological activities remain to be defined. The present study evaluates the anxiolytic, anticonvulsant, antidepressant, sedative effects produced by the extracts of Byrsonima crassifolia, and their influence on motor activity in ICR mice. Additionally, we determine the acute toxicity profiles of the Byrsonima crassifolia extracts and the presence of neuroactive constituents. Our results show that the methanolic extract of Byrsonima crassifolia produces a significant (P < 0.05) antidepressant effect in the forced swimming test in mice at 500 mg/kg dose. However, it does not possess anxiolytic, sedative, or anticonvulsant properties, and does not cause a reduction of mice locomotion (P > 0.05). Although the main compound of the methanolic extract was identified as quercetin 3-O-xyloside (12 mg/kg), our findings suggest that flavonoids, such as rutin (4.4 mg/kg), quercetin (1.4 mg/kg) and hesperidin (0.7 mg/kg), may be involved in the antidepressant effects. To the best of our knowledge, the present study constitutes the first report on the presence of the flavonoids with neuropharmacological activity rutin and hesperidin in Byrsonima crassifolia. In conclusion, the present results showed that the methanolic extract standardized on flavonoids content of Byrsonima crassifolia possesses potential antidepressant-like effects in the FST in mice, and could be considered as relatively safe toxicologically with no deaths of mice when orally administered at 2000 mg/kg.
The sedative–hypnotic effect of Caulis Polygoni multiflori decoction (CPMD) was studied by the rolling cylinder method in mice and by the somnopolygraphic recording method in rats. The result from the rolling method in mice showed that CPMD (9g/kg) did have synergic action with the subthreshold hypnotic dose of sodium pentobarbital (20mg/kg). The result from the somnopolygraphic recording experiment showed that the immediate hypnotic effect of an effective dose of CPMD (20g/kg) was basically similar to that of diazepam (5mg/kg) used under the same experimental condition, chiefly an increase in the duration of slow wave sleep phase (SWS) and a decrease in the duration of paradoxical sleep phase (PS). By the end of a three-day session in dose of twice a day the hypnotic effect appeared more prominent and the reduction of SWS latency became significant.
Objective: To invest the effects of Caulis Polygoni Multiflori.decoction on sleeping state of free-moving rats.Methods: After intragastric administration of Caulis Polygoni Multiflori.decoction(equivalent to 20g/kg crude drug) for 7 days,Polysomnography was used to record the changes of EEG of different sleeping states in rat.Results: After administration of Caulis Polygoni Multiflori.decoction,total sleeping time was increased in free-moving rats(P0.01),SWS1 and SWS2 was obviously increased on sleeping states but REMS changed insignificantly.Conclusion: The decoction of Caulis Polygoni Multiflori.has influence on sleeping state of normal rats and has improving-sleep effect.
Salvia guaranitica St. Hil. is a traditional medicinal plant used in Latin America as sedative. We have recently demonstrated the presence of cirsiliol in its extracts and found that this flavonoid is a competitive low affinity benzodiazepine receptor ligand (Marder et al., 1996). This report describes the pharmacological properties of Salvia guaranitica extracts and of its active principle, cirsiliol. A partially purified fraction of this plant, administered intraperitoneally in mice (in a dose equivalent to 3 g of the fresh plant), exhibited sedative and hypnotic effects as measured in the hole board and in the pentobarbital-induced sleep tests, respectively. On the other hand, this fraction had no anxiolytic or myorelaxant effects. In the pentobarbital-induced sleep test, cirsiliol (2–10mg/kg, i. p.) exhibited a dose-dependent hypnotic action. In contrast, it did not produce myorelaxant (up to 30mg/kg) or anticonvulsant (up to 10mg/kg) effects. Cirsiliol was found to be more potent in displacing 3H Zolpidem binding (Ki = 20 LiM) than 3H flunitrazepam binding (Ki = 200 μM) to benzodiazepine receptors from rat cerebral cortex.
It is concluded that Salvia guaranitica extracts and its active principle cirsiliol, possess sedative and hypnotic properties; cirsiliol produces these effects probably acting on the so-called type I benzodiazepine receptor.
Sedatives are agents that reduce anxiety and exert a calming effect with little or no effect on motor or mental functions. Hypnotics are drugs that produce drowsiness and encourage the onset and maintenance of a state of sleep that as far as possible resembles the natural state of sleep. Hypnotics involve more pronounced depression of the central nervous system than sedatives. By increasing the dose, most sedatives can act as hypnotics. Animal studies have been able to confirm the action of well known herbal sedatives and hypnotics such as Humulus lupulus, Melissa officinalis, Piper methysticum, Salvia guaranitica, Passiflora spp, Matricaria recutita, Anthemis nobilis and Valeriana spp. Studies using individual constituents versus whole plant extracts did not always yield the same results; in some cases the individual constituents were able to induce sleep and increase sleeping times of animals treated or not treated with hexobarbital and pentobarbital while others were not. Thus it has been difficult to isolate the constituent/s responsible for the sedative and hypnotic activity seen in these herbs. (author abstract)
Cordycepin (3′-deoxyadenosine) is a naturally occurring adenosine analogue and one of the bioactive constituents isolated from Cordyceps militaris/Cordyceps sinensis, species of the fungal genus Cordyceps. It has traditionally been a prized Chinese folk medicine for the human well-being. Because of similarity of chemical structure of adenosine, cordycepin has been focused on the diverse effects of the central nervous systems (CNSs), like sleep regulation. Therefore, this study was undertaken to know whether cordycepin increases the natural sleep in rats, and its effect is mediated by adenosine receptors (ARs). Sleep was recorded using electroencephalogram (EEG) for 4 hours after oral administration of cordycepin in rats. Sleep architecture and EEG power spectra were analyzed. Cordycepin reduced sleep-wake cycles and increased nonrapid eye movement (NREM) sleep. Interestingly, cordycepin increased θ (theta) waves power density during NREM sleep. In addition, the protein levels of AR subtypes (A1, A2A, and A2B) were increased after the administration of cordycepin, especially in the rat hypothalamus which plays an important role in sleep regulation. Therefore, we suggest that cordycepin increases theta waves power density during NREM sleep via nonspecific AR in rats. In addition, this experiment can provide basic evidence that cordycepin may be helpful for sleep-disturbed subjects.
There are 18 kinds of amino acids in C. sinensis and they mainly played a sedative hypnotic effect. Tryptophan is the most effective ingredient among them. Tryptophan is the precursor of serotonin material, which has close relationship with animals’ insomnia [98]. Otherwise, glutamic acid has the effect of immune inhibition. Due to the performance of the combined effect being more complex, more research needs to be explored.
Sedatives and hypnotics made from Chinese herbal medicine show great market prospects for minor side effects and zero potential addiction. In this study, the extraction conditions of Cordyceps militaris polysaccharide (CMP) and flavonoids (CMF) were, respectively, optimized by orthogonal experiments as follows: 30:1 ratio of water to plant material, three rounds of extraction at 90 °C and 3 h for each extraction; 40:1 ratio of 70% ethanol to plant material, reflux extraction at 90 °C for 4 h. Then, 200, 100 and 50 mg/kg of CMP and CMF were given intragastrically to mice for 30 days. The locomotor activity times of the mice were recorded on the 14th and 30th days. The effects of CMP and CMF on the sleep induced by pentobarbital sodium were observed on the 30th day. 5-Hydroxytryptamine (5-HT), acetylcholine (ACh), glutamate (Glu) and γ-aminobutyric acid (GABA) levels in the mouse brains were determined by enzyme-linked immunosorbent assay on the 30th day. The results showed that different doses of CMP and CMF could reduce the number of locomotor activities in mice and lower the Glu level (p < 0.05 in the 50 mg/kg CMP group and p < 0.01 in the other groups), elevate the 5-HT level and reduce the ACh level (p < 0.01 only in the 200 mg/kg CMP and CMF groups) in the mouse brains. Therefore, the elevated 5-HT levels and decreased ACh and Glu levels in the brains may be the main mechanisms through which CMP and CMF exert their sedative and hypnotic effects.
Abstract Background: Coriandrum sativum L. has been recommended for relief of insomnia in Iranian traditional medicine. However, no pharmacological studies have yet evaluated its sedative effects. The aim of this study was to determine if extracts and essential oil of coriander seeds have sedative–hypnotic activity. Methods: The aqueous or hydro-alcoholic extracts or essential oil of coriander seeds (100, 200, 400 and 600 mg/kg) were intraperitoneally administered to male albino mice, 30 minutes before pentobarbital injection (40 mg/kg). Latency to sleep and sleep duration were recorded. Results: Aqueous extract prolonged pentobarbital-induced sleeping time at 200, 400 and 600 mg/kg. Hydro-alcoholic extract at doses of 400 and 600 mg/kg increased pentobarbitalinduced sleeping time compared to saline-treated group. The essential oil increased pentobarbital-induced sleeping time only at 600 mg/kg. Conclusion: The extracts and essential oil of coriander seeds possess sedative–hypnotic activity. However, it is strongly suggested that the major active component(s) responsible for the hypnotic effect is mainly present in the aqueous extract.
The aim of the present study was to evaluate hypnotic effect of Coriandrum sativum, Ziziphus jujuba, Lavandula angustifolia and Melissa officinalis hydroalcoholic extracts in mice to select the most effective ones for a combination formula. Three doses of the extracts (250, 500 and 1000 mg/kg of C. sativum and Z. jujuba and 200, 400 and 800 mg/kg of L. angustifolia and M. officinalis) were orally administered to male Swiss mice (20-25 g) and one hour later pentobarbital (50 mg/kg, i.p.) was injected to induce sleep. Onset of sleep and its duration were measured and compared. Control animals and reference group received vehicle (10 ml/kg, p.o.) and diazepam (3 mg/kg, i.p.), respectively. C. sativum and Z. jujuba failed to change sleep parameters. L. angustifolia at doses of 200, 400 and 800 mg/kg shortened sleep onset by 7.6%, 50% and 51.5% and prolonged sleep duration by 9.9%, 43.1% and 80.2%, respectively. Compared with control group the same doses of M. officinalis also decreased sleep onset by 24.7%, 27.5% and 51.2% and prolonged sleep duration by 37.9%, 68.7% and 131.7% respectively. Combinations of L. angustifolia and M. officinalis extracts showed additive effect and it is suggested that a preparation containing both extracts may be useful for insomnia.
The present study was planned to investigate sleep-prolonging effect of C. sativum. The hydro-alcoholic extract (HAE) and its three fractions namely water (WF), ethyl acetate (EAF) and N-butanol (NBF) were prepared from C. sativum aerial parts and administrated to mice. Also, the possible cytotoxicity of the extracts was tested using cultured PC12 cells. The HAE, EAF and NBF significantly prolonged sleep duration. Only the NBF could significantly decrease sleep latency. No decrease in the neuronal surviving was observed either by HAE or by its fractions. The present data indicate that C. sativum exert sleep-prolonging action without major neurotoxic effect.
The clinical applications of benzodiazepines as anxiolytics are limited by their unwanted side effects. Therefore, the development of new pharmacological agents is well justified. Among medicinal plants, Coriandrum sativum L. has been recommended for relief of anxiety and insomnia in Iranian folk medicine. Nevertheless, no pharmacological studies have thus far evaluated its effects on central nervous system. Therefore, the aim of this study was to examine if the aqueous extract of Coriandrum sativum seed has anxiolytic effect in mice. Additionally, its analgesic effect was evaluated. The anxiolytic effect of aqueous extract (50, 100, 200 mg/kg, i.p.) was examined in male albino mice using elevated plus- maze as an animal model of anxiety. The effects of the extract on analgesic activity were assessed using Hot plate method. In the elevated plus-maze, aqueous extract at 200 mg/kg showed an anxiolytic effect by increasing the time spent on open arms and the percentage of open arm entries, compared to control group. Aqueous extract at 50, 100 and 200 mg/kg significantly produce analgesic activity compared to control group.These results suggest that the aqueous extract of Coriandrum sativum seed has anxiolytic effect and may have potential sedative and muscle relaxant effects.
The purpose of this study was to investigate the anxiolytic effects of tetrahydropalmatine (THP) and its potential interaction with the benzodiazepine binding site on the gamma-aminobutyric acid (GABAA) receptor in the male Sprague-Dawley rat. Tetrahydropalmatine (THP), an active component isolated from the Chinese herbal plant Corydalis yanhusuo, is used in Asia for its analgesic, sedative, and hypnotic properties during herbal therapy. Fifty-five rats were assigned to 1 of 5 groups with 11 rats per group: 1) control (vehicle), 2) THP, 3) midazolam, 4) midazolam with THP, and 5) flumazenil with THP. In this study, the elevated plus-maze measured the behavioral components of anxiety and motor movements. The data were analyzed using a 2-tailed multivariate analysis of variance to determine if a significant difference existed followed by the least significant difference post hoc test. The findings suggest that THP, 25 mg/kg, given via intraperitoneal injection, results in significant anxiolysis and decreased motor movements. Furthermore, flumazenil, 3 mg/kg, does not fully antagonize the effects of THP.
Rationale: Levo-tetrahydropalmatine (l-THP), an active ingredient of Corydalis yanhusuo, has been reported to be a partial agonist for dopamine D1 receptors (D1R) and an antagonist for D2R. Although it has been safely used clinically in China for decades as an analgesic with sedative/hypnotic properties, there are few studies that address the mechanisms by which l-THP exerts its beneficial effects in chronic pain-induced sleep disturbance.
Objectives: To investigate the effects and mechanisms of l-THP on sleep disturbance in a neuropathic pain-like condition.
Methods: A mouse model of chronic neuropathic pain induced by partial sciatic nerve ligation (PSNL) was employed. The antinociceptive and hypnotic effects of l-THP were evaluated by measurement of mechanical allodynia, thermal hyperalgesia, and electroencephalogram (EEG) recordings in PSNL mice. Pharmacological approaches and c-Fos expression were used to clarify the mechanisms of l-THP.
Results: Intraperitoneal injection of l-THP at 5 and 10 mg/kg not only significantly increased the mechanical threshold by 134.4% and 174.8%, and prolonged the thermal latency by 49.4% and 69.2%, but also increased non-rapid eye movement sleep by 17.5% and 29.6%, and decreased sleep fragmentation in PSNL mice, compared with the vehicle control. Moreover, the antinociceptive effect of l-THP was prevented by D1R antagonist SCH23390 or D2R agonist quinpirole; meanwhile, the hypnotic effect of l-THP was blocked by quinpirole rather than by SCH23390. Immunohistochemistry demonstrated that l-THP inhibited c-Fos overexpression induced by PSNL in the cingulate cortex and the periaqueductal gray.
Conclusions: These findings indicated that l-THP exerted analgesic effects by agonism D1R and antagonism D2R, and the antagonism of D2R mediated the hypnotic effect of l-THP in PSNL mice.
dl-Tetrahydropalmatine (dl-THP), a naturally occurring alkaloid, has been intensively studied for its sedative and hypnotic effects. Putative explanation for its mechanism and target of action involves the dopaminergicneurotransmission system. In view of the close interactions between the dopaminergic and the GABAergic neurons in the amygdala, pharmacological effects of dl-THP were tested for activity at the GABAA receptor benzodiazepine site (BDS). Effects of dl-THP were examined in mice employing the elevated plus-maze, the holeboard and the horizontal-wire tests. In the elevated plus-maze, mice treated with low doses of dl-THP (0.5–10 mg/kg) exhibited significant increase in the percentage of entries and time spent in open arms without altering the number of closed-arm entries when compared to the control group, indicative of its selective anxiolytic effect. In the holeboard and horizontal wire tests, where exploratory behavior and potential muscle relaxant effect were assessed, respectively, only mice treated with as much as 50 mg/kg dl-THP manifested sedation and myorelaxation, as observed in the significant decrease in the number of head dips and the decrease in the percentage of mice grasping wire in comparison to control. Notably, coadministration of the BDS antagonist flumazenil abolished the dl-THP-induced anxiolysis as seen in the reversal of the increase of both the number of entries and time spent in open arms back to basal levels in the elevated plus-maze test. The results suggest that dl-THP at defined low dosages acts as anxiolytics in mice, and the BDS mediates, at least in part, such anxiolytic effect of dl-THP.
Research in the area of herbal psychopharmacology has clearly improved in recent decades. Self-administration of herbal medicines has been the most popular therapeutic alternative to standard medicine.
Since the extract of Echium amoenum exhibits an anxiolytic effect, the aim of this study is to evaluate the anxiolytic and hypnotic effects in mice of the aqueous and ethanolic extracts of aerial parts of E. italicum, a member of the Boraginaceae family.
Mice were administered the agents intraperitoneally before the start of the experiments for evaluation of hypnotic activity (induced by sodium pentobarbital, 30 mg/kg, i.p.), anxiolytic activity (elevated plus-maze [EPM] test), locomotor activity (open field test), and motor coordination (rotarod test).
The ethanolic and aqueous extracts of E. italicum, at doses of 1.2 and 2.1 g/kg, increased the percentage of time-spent and the percentage of arm entries in the open arms of the EPM and decreased the percentage of time-spent in the closed arms of the EPM. Moreover, both extracts decreased the pentobarbital-induced latency to sleep and significantly increased the total sleeping time induced by pentobarbital. In addition, locomotor activity was affected by aqueous extracts and ethanolic extract (at higher doses). Both extracts showed no effect in the rotarod test.
Conclusions
These results suggest that both ethanolic and aqueous extracts of E. italicum may have anxiolytic effects and sedative activity but no effect on muscle relaxation.
Anxiolytic-like effects of dietary flavonoids are relatively well known. Ellagic acid is a naturally occurring flavonoid compound which is abundant in many plants and fruits. The present study was designed to investigate the antianxiety-like effect of ellagic acid in mice using an elevated plus-maze test. The involvement of the GABAergic and serotonergic systems in the antianxiety-like activity of ellagic acid was also studied. Our results showed that ellagic acid treatment (25, 50 and 100 mg/kg, p.o.), produced a significant increase in the percentage of time spent and entry into the open arms, with a profile comparable to that of diazepam (1 mg/kg, p.o.). Unlike diazepam, the anxiolytic doses of ellagic acid did not prolong the duration of sodium thiopental-induced loss of righting reflex, indicating that this flavonoid is non-hypnotic. The anxiolytic effect observed with ellagic acid treatment (25 mg/kg, p.o.) was antagonized by pretreatment with picrotoxin (a non-competitive GABAAreceptor antagonist, 1 mg/kg, i.p.) and flumazenil (a benzodiazepine site antagonist, 1 mg/kg, i.p.) but not with p-chlorophenylalanine (a serotonin synthesis inhibitor, 100 mg/kg, i.p.) and pindolol (a β-adrenoceptors blocker/5-HT1A/1B receptor antagonist, 10 mg/kg, i.p.). Taken together, the data demonstrated that acute and chronic administration of ellagic acid to mice has produced antianxiety-like effect when tested in the elevated plus-maze. The experiments with different receptor blockers suggest an involvement of GABAergic system in the anxiolytic action of this bioflavonoid. However, this action is not seems to be mediated through serotonergic system.
With the problem of insomnia becoming more serious and the disadvantages of sedative and hypnotic drugs gotten by chemical synthesis becoming more obvious, Chinese herbal medicines with the function of improving sleep quality are getting more and more attention. A large number of Chinese herbal medicines with the function of improving sleep quality were found and proved. These Chinese herbal medicines have the advantages of wide sources, high safety, little side effects, no dependence and so on. They have become the main objects of the domestic and foreign scholars. In this paper, Chinese herbal medicines with the function of improving sleep quality were summarized and the kinds of Chinese herbal medicines, active ingredients, extraction methods, assay methods of the function of improving sleep quality and mechanism of action were introduced.
The main pharmacological effects of sedative agents are sedation,hypnosis, antianxiety, and antidepression. Traditional Chinese medicine (TCM) has a long history of clinical experience in treating insomnia. This review focuses mainly on the role of active ingredients from TCM in the treatment of insomnia. Single herbs and their active ingredients from TCM withhypnoticeffects are summarized through reviewing the relevant literature published in the past 20 y. The active ingredients are divided into alkaloids, terpenoids, and volatile oils, flavonoids, lignanoids and coumarins, saponins, and others. Current studies on TCM in treating insomnia are described from the aspects of active ingredients, sources, experimental models and methods, results, and mechanisms. In addition, Chinese compound prescriptions developed from a variety of single herbs with sedative–hypnotic effects are introduced. The acting pathways of TCM are covered from the perspectives of regulating central neurotransmitters, influencing sleep-related cytokines, and improving the structure of the central nervous system.
Ganoderma has multiple pharmacological activities and clinical uses. The aqueous extract of G. lucidum (Curt.: Fr.) P. Karst. spores also has many pharmacological activities and clinical uses. The injection made from the spores of G. lucidum (called Jisheng injection) has been used clinically for more than 20 years for its therapeutic effects on several neuromuscular disorders such as myotonia and polymyositis. Jisheng injection can gradually improve a patient’s sleep and enhance appetite after he or she takes it for about 2 weeks. To determine the pharmacological bases of the clinical effect of Jisheng injection in improving patients’ sleep, the authors investigated the hypnotic and sedative effects of Jisheng injection on the central nervous system in mice. The results are as follows: (1) subcutaneous injection of Jisheng extract significantly prolonged the sleeping time induced by both sodium pentobarbital and barbital in mice in a dose-dependent manner; (2) Jisheng extract also induced sleep in mice after intraperitoneal injection of a subthreshold dose of pentobarbital which could not induce sleep in normal mice; (3) repeated injection of the effectively hypnotic dosage of Jisheng extract once daily for 8 consecutive days did not induce addiction, as the prolonging effect of Jisheng on pentobarbital sleeping time was not shortened, whereas the chemical hypnotic drug diazepam induced addiction after repeated injection for 8 days; and (4) Jisheng injection markedly decreased the spontaneous motor activity in mice. It may be concluded from these results that the aqueous extract of G. lucidum spores has hypnotic and sedative actions on the central nervous system in mice.
Inflammation and insomnia are two types of symptoms very likely occur in life, seriously perplexing people’s work and life. How to alleviate these symptoms is an urgent medical problem. Lucidone D (LUC) is a terpene from the ethanol extract of Ganoderma lucidum fruiting body. Triterpenoids are also the main pharmacological components of Ganoderma lucidum. In recent years, people pay more and more attention to its anti-inflammatory effect. In this study, LPS induced RAW264.7 macrophage inflammatory response model was used to evaluate the anti-inflammatory activity of LUC. The results showed that LUC could significantly inhibit the production of inflammatory mediators NO, which may play a role by down-regulating the expression level of iNOS and COX-2 proteins. Meanwhile, the production of TNF-α and IL-6 was significantly inhibited. These results indicate that LUC has obvious anti-inflammatory activity. Writhing and sedation tests in ICR male mice showed that LUC showed significant analgesic and sedative effects. In conclusion, these results suggest the anti-inflammatory, analgesic and sedative effects of LUC in vitro and in vivo.
These results suggest that GLE has hypnotic effects in freely moving rats. The mechanism by which the extract promoted sleep remains unclear, but this effect appears to be primarily related to the modulation of cytokines such as TNF-α. Furthermore, these data at least partially support the ethnomedical use of Ganoderma lucidum.
Objective:To observe the effects of Ganoderma Lucidum Granules on the sedation, hypnosis and immune function in mice. Methods: Open field method, Sleep – promoting test in combination with pentobarbital sodium, anti -convulsant activity,determining the spleen index and chest gland index,the amount of the white blood cells(WBC). Results:It can obviously reducing the autonomic activity,and promoting sleep in combination with pentobarbital sodium, anti – convulsant activity, obviously increase the spleen index and chest gland index, the amount of the WBC. Conclusion:It has the effects of sedation, hypnosis and strengthening immune function.
Objective To investigate the sedative and hypnotic effects of Ganoderma lucidum brewage(GLB).Methods The NIH mice were given with gavage of GLB 0.06,0.12,and 0.24g/kg per day respectively for 15 days.The spontaneous motion,the sleeping time induced by pentobarbital sodium in subthreshold dosage and threshold dosage,and the number of mice subjected to pentylenetetrazol-induced convulsion were observed.Results GLB can reduce the spontaneous motion,significantly longthen the mice sleeping time of pentobarbital sodium in threshold dosage and increase the number of sleeping mice under subthreshold dosage of pentobarbital sodium.GLB was synergic with pentobarbital sodium,and antagonized pentylenetetrazol-induced convulsion in a dose-dependent manner.Conclusion GLB possesses obvious sedative,hypnotic and anticonvulsive effects.
Inflammation and insomnia are two types of symptoms very likely occur in life, seriously perplexing people’s work and life. How to alleviate these symptoms is an urgent medical problem. Lucidone D (LUC) is a terpene from the ethanol extract of Ganoderma lucidum fruiting body. Triterpenoids are also the main pharmacological components of Ganoderma lucidum. In recent years, people pay more and more attention to its anti-inflammatory effect. In this study, LPS induced RAW264.7 macrophage inflammatory response model was used to evaluate the anti-inflammatory activity of LUC. The results showed that LUC could significantly inhibit the production of inflammatory mediators NO, which may play a role by down-regulating the expression level of iNOS and COX-2 proteins. Meanwhile, the production of TNF-α and IL-6 was significantly inhibited. These results indicate that LUC has obvious anti-inflammatory activity. Writhing and sedation tests in ICR male mice showed that LUC showed significant analgesic and sedative effects. In conclusion, these results suggest the anti-inflammatory, analgesic and sedative effects of LUC in vitro and in vivo.
The rhizomes of Gastrodia elata have been used for the treatment of insomnia in oriental countries. N6-(4-hydroxybenzyl) adenine riboside (NHBA) was originally isolated from G. elata. For the first time we report a detailed study on the effects and mechanisms of NHBA on its sedative and hypnotic activity. Adenosine, an endogenous sleep factor, regulates sleep–wake cycle via interacting with adenosine A1/A2A receptors. Using radioligand binding studies and cAMP accumulation assays, our results show that NHBA may be a functional ligand for the adenosine A1 and A2A receptors. NHBA significantly decreases spontaneous locomotor activity and potentiates the hypnotic effect of sodium pentobarbital in mice. Sleep architecture analyses reveal that NHBA significantly decreases wakefulness time and increases NREM sleep times. However, NHBA does not affect the amount of REM sleep. Pretreatment with the adenosine A1 receptor antagonist DPCPX or the A2A receptor antagonist SCH 58261 significantly reverses the increase in sleeping time induced by NHBA in sodium pentobarbital treated mice. Immunohistochemical studies show that NHBA increases c-Fos expression in GABAergic neurons of the ventrolateral preoptic area (VLPO), which suggests that NHBA activates the sleep center in the anterior hypothalamus. Altogether, these results indicate that NHBA produces significant sedative and hypnotic effects. Such effects might be mediated by the activation of adenosine A1/A2A receptors and stimulation of the sleep center VLPO.
Highlights
► NHBA, active compound of Gastrodia elata, possesses sedative and hypnotic effects. ► Adenosine A1/A2A receptors may be involved in the hypnotic effect of NHBA. ► NHBA significantly activates the sleep center VLPO in the anterior hypothalamus.
Objective To observe the sedative and hypnotic effect of gastrodin in mice.Methods Effects of gastrodin on the autonomous activity of mice and synergy of gastrodin and sodium pentobarbital were tested.Results Gastrodin obviously decreased the times of autonomous activity of mice,and increased the subthreshold dose of sodium pentobarbital to mouse sleep.Conclusion Gastrodin has obvious effects on the sedation and hypnosis of mice.
Gastrodin have been extensively investigated on its biological actions. As a result, numerous pharmacological activities have been attributed to gastrodin, including sedative, hypnotic (Deng and Mo, 1979), anti-vertigo (Chen et al., 2004), analgesic (Zhang et al., 2006), anti-epileptic (Ojemann et al., 2006), antidepressant (Chen and Sheen, 2011), anxiolytic (Peng et al., 2013), memory-improving (Hsieh et al., 1997), anti-aging (Wang Z. J. et al., 2007), lowering blood pressure (Zhang Q. et al., 2008), preventing osteonecrosis (Zheng et al., 2014) effects, etc. Among its various pharmacological properties, its strong actions in CNS diseases appear to be particularly prominent. Considering its low toxicity and remarkable pharmacological performance, gastrodin might be a potential valuable therapeutic for the prevention and treatment of some CNS disorders (Zhan et al., 2016).
Gastrodin is extracted from Gastrodia elata, which is widely used for the treatment of vertigo, headache, neuralgia, neurasthenia syndrome, and brain traumatic syndrome. Studies showed that gastrodin has many pharmacological effects, including hypnosis, sedation, and anticonvulsive.
Sleep disorder may have detrimental consequences on health and one of the treatments is the use of hypnotics. Unfortunately, hypnotics treatment may also be accompanied by side effects and lead to dependence. The present study aimed to investigate the sleep improving effects of ethanol extract of Gardenia augusta (L.) Merr. flowers in rat model. Methods: Rats were assigned into group receiving the extract (at 0.9 or 1.8 g/kg), the reference drug crocetin (at 0.9 mg/kg) or vehicle, once a day orally for 15 days. Results: Tested on day 1 and 14 of treatment, the rats receiving 1.8 g/kg of the extract showed improvements in sleep latency, sleep duration, sleep efficiency, wake episodes, and sleep cycle, which were significantly different from crocetin. Furthermore, tested on day 2 and 15 of treatment, the rats treated with 1.8 g/kg extract demonstrated superior sedative rating scale compared to crocetin. Conclusions: Results of the present study indicates the potential of Gardenia augusta (L.) Merr. flower extract to be used as an adjunct treatment for sleep disorder. Key words: Sleep, Improvement, Gardenia augusta (L.) Merr., Flowers, Rats.
The literature (98) has reported sedative–hypnotic activity of hispidulin. Plentiful flavonoids from terrestrial plants have been reported with their affinity for BZD site of GABAA receptors (99). In vitro analysis of different substitutions particularly on flavone structure for their affinity to BZD site of GABAA receptor has also been reported (100); an increase in binding affinity has been stated for 6- methoxylation (hispidulin), whereas 7- or 3- methoxylation resulted in significant decrease in activity (see Fig. 2). This makes hispidulin superior compared to crisimaritin (7-methoxy compound) and galangin-3-methyl ether (3-methoxy compound) in binding affinity for BZD site of GABAA receptor. Hispidulin has also been reported from sedative plants with binding affinity value of 8 µM (89). In traditional medicine, this plant is applied as a sedative, hypnotic, expectorant, coughs suppressant, purgative, diuretic, antiseptic, vasorelaxant, and antispasmodic (9).
Licorice (Glycyrrhiza glabra, GG) is one of the most frequently used herbal medicines worldwide, and its various biological activities have been widely studied. GG is reported to have neurological properties such as antidepressant, anxiolytic, and anticonvulsant effects. However, its hypnotic effects and the mechanism of GG and its active compounds have not yet been demonstrated. In this study, GG ethanol extract (GGE) dose-dependently potentiated pentobarbital-induced sleep and increased the amount of non-rapid eye movement sleep in mice without decreasing delta activity. The hypnotic effect of GGE was completely inhibited by flumazenil, which is a well-known γ-aminobutyric acid type A-benzodiazepine (GABAA-BZD) receptor antagonist, similar to other GABAA-BZD receptor agonists (e.g., diazepam and zolpidem). The major flavonoid glabrol was isolated from the flavonoid-rich fraction of GGE; it inhibited [3H] flumazenil binding to the GABAA-BZD receptors in rat cerebral cortex membrane with a binding affinity (Ki) of 1.63 μM. The molecular structure and pharmacophore model of glabrol and liquiritigenin indicate that the isoprenyl groups of glabrol may play a key role in binding to GABAA-BZD receptors. Glabrol increased sleep duration and decreased sleep latency in a dose-dependent manner (5, 10, 25, and 50 mg/kg); its hypnotic effect was also blocked by flumazenil. The results imply that GGE and its flavonoid glabrol induce sleep via a positive allosteric modulation of GABAA-BZD receptors.
Phytol, a diterpenoid isolated from the ethanolic fraction of Jasminum officinalle was found to raise the levels of gamma-aminobutyric acid, a sleeppromoting neurotransmitter, in the brain (Bang et al., 2012). The calculated LD50 and the acute toxicity both invivo and invitro study indicates that the plant is safe and have a wild range of therapeutic dose. Therefore, the hypnotic effect of Jasminum officinalle accompanied with no neurotoxicity, leading to further support of its safety. In conclusion, results obtained in the study is achieved or set up for the first time to demonstrate the jasmine prolongation of the induction in the sleeping period behavior caused by pentobarbital in experimental animals model. The sleep prolonging effect was comparable to that of induced by diazepam and accompanied with no neuron toxicity. The most chemical constituents shows the hypnotic activity is non-polar agents found in NBF. Isolation of the exact component that produce and yield a new sedative–hypnotic drug is required in future.
Objective To evaluate the role of Arabian jasmine volatile oil in the improvement of sleep quality and assess its calm and hypnotic effects.Methods 45 healthy volunteers were allocated to receive Arabian jasmine volatile oil.Before and after Arabian jasmine volatile oil treatment,the volunteers’ sleep quality was assessed by PSQI.Results After treatment with Arabian jasmine volatile oil,the Pittsburgh sleep quality index could be improved in 45 healthy volunteers.Especialy in sleep disorder groups,the PSQI could be recovered,and the sleep disorder,hypnotige drugs and function of daytime were improved too.Conclusion Arabian jasmine volatile oil can improve the sleep quality.
Insomnia is the most common sleep disorder. The present study was carried out to evaluate the sedative–hypnotic effect of hydro-alcoholic extract (HAE) of lettuce and its water fraction (WF), ethyl acetate fraction (EAF) and n-butanol fraction (NBF). Extract and its fractions were injected to mice 30 min before the pentobarbital. Additionally, the effects of flumazenil on the hypnotic activity of the extract and its toxic effect were determined in vivo and in vitro situations. The HAE prolonged the pentobarbital-induced sleep duration at doses of 50-400 mg/kg (50 mg/kg; P<0.05, 100 and 200 mg/kg; P<0.01). In comparison to the control group, HAE at dose of 400 mg/kg increased sleeping time more than diazepam (P<0.001 vs control). Also flumazenil (2 mg/kg) reversed the effects of both diazepam (P<0.001 vs diazepam group) and 400 mg/kg of HAE (P<0.001 vs HAE group). The NBF was the only fraction which could increase sleep duration (P<0.001) and decrease sleep latency (P<0.001). Flumazenil reversed hypnotic effect of the extract and diazepam. The LD50-value for HAE was found to be 4.8 g/Kg. HAE and its fractions did not show any neurotoxic effect in cultured PC12-cell line. HPLC profile of the extract showed five major peaks with different retention times. The results suggested that Lactuca serriola potentiated pentobarbital hypnosis without major toxic effect. Most probably, the main component (s) responsible for this effect was most likely to be non-polar agent (s) which is found in NBF of this plant.
Nine Lilium samples (belong to 6 different cultivars with different maturity stage) were qualitatively and quantitatively analyzed of total phenolics (TP), total flavonoids (TF), total saponins (TS), total carbohydrates (TC, polysaccharides), and soluble proteins contents (SP), and the monomeric components were quantified utilizing high‐performance liquid chromatography with photodiode array detector (HPLC‐PAD) associated with liquid chromatography–mass spectrometry (HPLC‐MS). Antioxidant activity (reducing power and DPPH radical scavenging activity), anti‐inflammatory (xylene‐induced mouse ear edema detumescent assay and carrageenan‐induced mouse paw edema detumescent assay), and sedative‐hypnotic capacities (sodium pentobarbital‐induced sleep assay) were comparatively evaluated in mouse model. Additionally, correlation analysis and principal component analysis were carried out to detect clustering and elucidate relationships between components’ concentrations and bioactivities to clarify the role of effective composition. Lilium bulbs in later maturity stage preliminary evidenced higher saponins content, and lower phenolic acids and flavonoids content. The result demonstrated that Lilium bulbs generally had distinct antioxidant, anti‐inflammatory, and sedative‐hypnotic capacities. Varieties statistically differed (P < 0.05) in chemical composition and bioactivities. Lilium varieties of Dongbei and Lanzhou presented potent sedative‐hypnotic effect and anti‐inflammatory activity. The antioxidant capacity was related to the phenolic acids and flavonoids contents, the anti‐inflammatory and sedative‐hypnotic capacities were related to the saponins content. This is first study presenting comprehensive description of common edible Lilium bulbs’ chemical compositions, sedative‐hypnotic, and anti‐inflammatory capacities grown in China. It would informatively benefit the genetic selection and cultivated optimization of Lilium varieties to improve nutritional quality, and promote Lilium bulbs as a therapeutic functional food worldwide.
To screen and analyze the hypnotic active ingredients of Lilium lancifolium Thunb.Methods:Direct sleep experiment and prolonged pentobarbital sleeping time experiment are used to study the hypnotic active ingredients of Lilium lancifolium Thunb. The hypnotic active ingredients are separated by separation column like macroporous resin column and MCI column. Magnetic resonance imaging(MRI) is used to identify the structure of active ingredients. The n-butanol extract of Lilium lancifolium Thunb can increase the rate and time of sleep,accelerate the sleep of mice. By separating,the main structure of the active ingredients are(25 R)-3β,17α-dihydroxy-5α-spirostan-6-one-3-O-α-L-Rhamnopyranosyl-(1 →2)-β-D-glucopyranoside and(25 R)-3β-hydroxy-5α-spirostan-6-one-3-O-zα-L-Rhamnopyranosyl-(1 →2)-β-D-glucopyranoside. The n-butanol extract of Lilium lancifolium Thunb has significant hypnotic effect and the structure of its main ingredients are saponins. LONGAN FRUIT PEEL(Dimocarpus longan Lour extract)CNS Depressant, Analgesic Effects of Different Solvent Extracts of Peel of Dimocarpus Longan Lour Fruits The results of phytochemical screening test of crude extrac
