Effect of crocus sativus L. (saffron) stigma and its constituents,crocin and safranal,on morphine withdrawal syndrome in mice

Crocus sativus L. has been shown to interact with the opioid system. Thus, the effects of aqueous and ethanolic extracts of stigma and its constituents were evaluated on morphine‐withdrawal syndrome in mice. Dependence was induced using subcutaneous (s.c.) injections of morphine for 3 days. On day 4, morphine was injected 0.5 h prior the interaperitoneal (i.p.) injections of the extracts, crocin, safranal, clonidine (0.3 mg/kg) or normal saline. Naloxone was injected (5 mg/kg i.p.) 2 h after the final dose of morphine and the number of episodes of jumping during 30 mm was considered as the intensity of the withdrawal syndrome. Clonidine, the aqueous and ethanolic extracts of saffron reduced the jumping activity. Safranal was injected (s.c.) 30 mm prior and 1 and 2 h after the injection of morphine. It potentiated some signs of withdrawal syndrome. The aqueous extract decreased the movement in all of the doses (80, 160, 320 mg/kg) and the ethanolic extract decreased it in the dose of 800 mg/kg in open field test. But crocin and the dose of 400 mg/kg ethanolic extract showed no effect on activity in this test. It is concluded that the extracts and crocin may have interaction with the opioid system to reduce withdrawal syndrome. Copyright © 2009 John Wiley & Sons, Ltd.     

Hypotensive effect of aqueous saffron extract (Crocus sativus L.) and its constituents,safranal and crocin,in normotensive and hypertensive rats

In this study, the effects of saffron (Crocus sativus) stigma aqueous extract and two active constituents, crocin and safranal, were investigated on blood pressure of normotensive and desoxycorticosterone acetate‐induced hypertensive rats. Three doses of crocin (50, 100 and 200 mg/kg), safranal (0.25, 0.5 and 1 mg/kg) and the aqueous extract (2.5, 5 and 10 mg/kg) were administered intravenously in different groups of normotensive and hypertensive animals and their effects on mean arterial blood pressure (MABP) and heart rate (HR) were evaluated. The aqueous extract of saffron stigma, safranal and crocin reduced the MABP in normotensive and hypertensive anaesthetized rats in a dose‐dependent manner. For example, administrations of 10 mg/kg of aqueous extract, 1 mg/kg of safranal and 200 mg/kg of crocin caused 60 ± 8.7, 50 ± 5.2 and 51 ± 3.8 mmHg reductions in MABP, respectively. It can be concluded that the aqueous extract of saffron stigma has hypotensive properties which appear to be attributable, in part, to the actions of two major constitutes of this plant, crocin and safranal. It seems that safranal is more important than crocin for lowering down blood pressure of rats. Copyright © 2009 John Wiley & Sons, Ltd.     

解郁丸抗焦虑及催眠作用的实验研究

目的：研究解郁丸的抗焦虑及催眠作用。方法：采用小鼠高架十字迷宫实验、应激导致孤养小鼠体温升高实验评价解郁丸的抗焦虑活性；戊巴比妥钠阈下催眠剂量实验和延长戊巴比妥钠睡眠时间实验评价其与戊巴比妥钠的协同作用。结果：解郁丸能增加小鼠在开臂内运动时间百分率和抑制应激所致孤养小鼠的体温升高，在小鼠高架十字迷宫与应激导致孤养小鼠体温升高模型上显示出抗焦虑作用；解郁丸对小鼠自主活动无影响，表明其在抗焦虑的剂量下无镇静的副作用。同时解郁丸亦能提高小鼠翻正反射消失数，增加小鼠入睡率；与戊巴比妥钠协同明显延长小鼠睡眠时间。结论：解郁丸有一定的抗焦虑及催眠作用。     

Central nervous system activity of yangambin from Ocotea duckei Vattimo (Lauraceae) in mice

This work presents behavioral effects of yangambin isolated from the leaves of Ocotea duckei on open field, rota rod, barbiturate sleeping time, forced swimming and elevated plus maze test in mice. Yangambin was intraperitoneally administered to male mice at single doses of 12.5, 25 and 50 mg/kg. The results showed that yangambin in the doses of 25 and 50 mg/kg decreased the locomotor activity and the number of rearing. However, no change was observed in the rota rod test between the yangambin groups as compared to the control group. Reduction on the sleep latency and a prolongation of the sleeping time induced by pentobarbital was observed only with the yangambin dose of 50 mg/kg. In the forced swimming test, yangambin (25 and 50 mg/kg) increased the immobility time. Yangambin, in the doses of 25 and 50 mg/kg, decreased the number of entries and the time of permanence in the open arms of the elevated plus maze test. However, this effect can not be related to anxiogenic effects, but to a decrease in locomotor activity. The results showed that yangambin presents a depressant activity in the open field, forced swimming and pentobarbital sleeping time tests. These effects probably were not due to peripheral neuromuscular blockade, since there was no alteration on the rota rod test. Also, no anxiolytic effect was observed after the treatment with yangambin.     

Anxiolytic‐like effects of standardized extract of Justicia pectoralis (SEJP) in mice: Involvement of GABA/benzodiazepine in receptor

Justicia pectoralis (Acanthaceae) is used as an antiinflammatory, antimicrobial and bronchodilator, and its extract exerts an anxiolytic‐like effect profile in animal models. This work presents the behavioral effects of an aqueous standardized extract of Justicia pectoralis (SEJP) in animal models, such as the elevated plus maze (EPM), light/dark, open field, rota rod and pentobarbital sleep time. The extract was administered intragastrically to male mice at single doses of 50, 100 and 200 mg/kg, while diazepam 1 or 2 mg/kg was used as a standard drug and flumazenil 2.5 mg/kg was used to evaluate the participation of benzodiazepinic receptors. The results showed that, similar to diazepam (1 mg/kg), SEJP significantly modified all the observed parameters in the EPM test, without altering the general motor activity in the open field, rota rod and pentobarbital sleep time tests. Flumazenil reversed not only the diazepam effect but also the SEJP effect. In the same way, all doses of SEJP increased the time of permanence in the light box in the light/dark test. The results showed that SEJP presented an anxiolytic‐like effect, disproving sedative effects. Copyright © 2010 John Wiley & Sons, Ltd.     

Saffron (Crocus sativus) aqueous extract and its constituent crocin reduces stress-induced anorexia in mice

In the present study, the effects of an ethanol and aqueous extract of saffron Crocus sativus and its constituents safranal and crocin on the stress‐induced reduction in food intake, weight gain and anorexic time in mice were investigated. Male albino mice (20–25 g) were irregularly exposed to a trial of electroshock stress for 7 days. Then, the anorexic time as well as the animal's food intake and weight were recorded. In addition, blood samples were obtained on days 1 and 7 for corticosterone determination. Intraperitoneal (i.p.) administration of the aqueous but not the ethanol extract (10, 50 and 100 mg/kg) significantly reduced the anorexic time. The results were similar for crocin (1, 5 and 10 mg/kg; i.p.). In addition, a reduction in weight gain was observed in the controls as well as in the groups that received alcohol extract or safranal. However, this was not observed in animals treated with aqueous extract or crocin. The plasma corticosterone level did not increase in the aqueous extract and crocin treated animals. It can be concluded that the saffron aqueous extract and its constituent crocin reduce side effects of electroshock stress in mice. Copyright © 2011 John Wiley & Sons, Ltd.     

Effects of extract of Cistus populifolius L. on the central nervous system.

We report the effects on the central nervous system (CNS) and on analgesic activity of an aqueous extract of Cistus populifolius L. The extract was assayed for effects on spontaneous locomotor activity, methylphenidate-induced hypermotility, motor coordination, exploratory behaviour, rectal temperature and sodium pentobarbital-induced hypnosis. Analgesic activity was evaluated using the hot plate test. The C. populifolius extract at dosages of 286 and 430 mg/kg caused very significant reductions in spontaneous locomotor activity, hypermotility, motor coordination, exploratory behaviour and rectal temperature, and a slight increase of sleeping time was noted in the sodium pentobarbital-induced sleep test. The extract exhibited central analgesic affects in the hot plate test.     

Coriandrum sativum: evaluation of its anxiolytic effect in the elevated plus-maze

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 effect on spontaneous activity and neuromuscular coordination were evaluated. The anxiolytic effect of aqueous extract (10, 25, 50, 100 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 spontaneous activity and neuromuscular coordination were assessed using Animex Activity Meter and rotarod, respectively. In the elevated plus-maze, aqueous extract at 100 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 500 mg/kg significantly reduced spontaneous activity and neuromuscular coordination, 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.     

Biphasic effects of Morus alba leaves green tea extract on mice in chronic forced swimming model

In this study, the effects of an aqueous extract of Morus alba leaves green tea (ME) on mouse behaviors (depression, anxiety, climbing activity and thermal response), muscle coordination and muscle strength were studied. Male IRC mice received a single intraperitoneal injection of either the ME, desipramine or diazepam. Thirty minutes after injection, the mice were tested in all experimental models. A significant antidepressant-like effect could be detected in the animals receiving either 100 or 200 mg/kg ME. The effect of 200 mg/kg ME in decreasing the immobility time was comparable to 10 mg/kg desipramine. With higher dose (1000 mg/kg), a significant increase in immobility time could be observed. In the elevated plus maze, no increase in time in the open arm could be observed in mice treated with ME at either 100 or 200 mg/kg. However, high doses of ME (500 or 1000 mg/kg) decreased both time in the open arm and the number of entries in the maze. No change in thermal response could be seen in mice treated with ME at doses up to 500 mg/kg, however, at 1000 mg/kg, the response time to heat was increased significantly. The ME at either 500 or 1000 mg/kg also decreased muscle coordination, strength and climbing activity significantly when compared with the control. This study suggests that ME possesses an antidepressant- without an anxiolytic-like effect, however, at high doses, the extract might show the sedative effect and alter other functions such as muscle strength, animal activity in the maze and pain response.     

Anxiolytic effects of the aqueous extract of Uncaria rhynchophylla

The purpose of this study was to characterize the putative anxiolytic-like effects of the aqueous extract of hooks with stem of Uncaria rhynchophylla using the elevated plus maze (EPM) and the hole-board apparatus in rats and mice. Control rats were treated with an equal volume of saline, and positive control rats with buspirone (1 mg/kg). Single or repeated treatments of the aqueous extract of Uncaria rhynchophylla (200 mg/kg/day, p.o.) for 7 days significantly increased the time-spent and entries into open arms of the EPM, and reduced the time-spent and entries into the closed arms versus saline controls (P<0.05). However, no changes in spontaneous locomotor activity or myorelaxant effects were observed versus saline controls. In the hole-board test, repeated treatment with the aqueous extract of Uncaria rhynchophylla (100 or 200 mg/kg/day, p.o.) significantly increased the number of head-dips (P<0.05). In addition, the anxiolytic-like effects of Uncaria rhynchophylla extract as assessed using the EPM test were abolished by WAY 100635 (0.3 mg/kg, i.p.), a 5-HT(1A) receptor antagonist. These results suggest that Uncaria rhynchophylla is an effective anxiolytic agent, and acts via the serotonergic nervous system.     

Central nervous system depressant activity of an ethyl acetate extract from Ipomoea stans roots

Ipomoea stans Cav., popularly known as "tumbavaqueros", is a plant widely used in Mexico for the treatment of epileptic seizures and nervous disorders. This work researched the action of the ethyl acetate extract from the root of I. stans (IS-EAE) on the central nervous system (CNS). The administration of IS-EAE (2.5 and 5.0 mg/kg, i.p.) produced an anxiolytic effect in mice. This extract (20.0 and 40.0 mg/kg, i.p.) significantly reduced spontaneous motor activity. 2.5, 5.0, 10.0, and 20.0 mg/kg of IS-EAE protected mice against pentylenetetrazole-induced convulsions and increased the hypnotic effect induced by pentobarbital. The administration of IS-EAE was able to increase the release of GABA in brain cortex of mice. These results suggest that IS-EAE possess anxiolytic and anticonvulsant effects, and could have potential sedative effect, probably through a GABAergic system. The extract did not show antidepressant effects on mice exposed to forced swimming test.     

Anticonvulsant,anxiolytic and sedative activities of the aqueous root extract of Securidaca longepedunculata Fresen.

Aim of the study

The objective of this study is to investigate the anticonvulsant, anxiolytic and sedative activities of the aqueous root extract of Securidaca longepedunculata.

Materials and methods

The anticonvulsant effect of the aqueous root extract (100, 200 and 400 mg/kg) was evaluated in mice using the strychnine- and picrotoxin-induced seizure models. Its anxiolytic activity was evaluated using the elevated plus maze (EPM) and the Y maze (YM) methods (14 and 32) while the hexobarbitone induced sleep and the hole board models were used to evaluate the sedative and exploratory activities in mice respectively. The acute toxicity studies and phytochemical analysis of the extract were also carried out.

Results

The extract (100–400 mg/kg) produced a significant (P < 0.01) dose dependent increase in onset of convulsion compared to the control for strychnine- and picrotoxin-induced seizures. It also produced a significant (P < 0.01) dose dependent prolongation of the cumulative time spent in the open arms of the elevated plus maze and Y maze compared with the control. The extract (100–400 mg/kg) produced significant (P < 0.01) reduction in the time of onset of sleep induced by hexobarbitone. The prolongation of hexobarbitone sleeping time by the extract (200 mg/kg) was comparable to that produced by diazepam (3 mg/kg). At doses of 100–400 mg/kg, the extract produced a dose dependent decrease in exploratory activity of the mice. The reduction in exploratory activity produced by the extract (400 mg/kg) was greater than that of chlorpromazine (1 mg/kg). The results obtained from the experiments indicate that the extract has central nervous system depressant and anxiolytic activities. The LD₅₀ obtained for the acute toxicity studies using both oral and intraperitoneal routes of administration were 1.74 g/kg and 19.95 mg/kg respectively.

Conclusion

These findings justify the use of Securidaca longepedunculata in traditional medicine for the management of convulsion and psychosis.     

Evaluation of anxiolytic and sedative effects of 80% ethanolic Carica papaya L. (Caricaceae) pulp extract in mice

Ethnopharmacological relevance

Carica papaya has been used in the Ethiopian traditional medicine to relieve stress and other disease conditions.

Aim of the study

The present study was undertaken to evaluate the anxiolytic and sedative effects of 80% ethanolic Carica papaya (Caricaceae) pulp extract in mice.

Materials and methods

Carica papaya pulp extract was screened for anxiolytic effect by using elevated plus maze, staircase and open field tests, and ketamine-induced sleeping time test for sedation at doses of 50, 100, 200, 400 mg/kg. Distilled water and Diazepam were employed as negative and positive control groups, respectively.

Results

Carica papaya pulp extract 100 mg/kg significantly increased the percentage of open arm time and entry, and reduced the percentage of entry and time spent in closed arm in elevated plus maze test; reduced the number of rearing in the staircase test; and increased the time spent and entries in the central squares while the total number of entries into the open field were not significantly affected, suggesting anxiolytic activity without altering locomotor and sedative effects. A synergistic reduction in the number of rearing and an inverted U-shaped dose response curves were obtained with important parameters of anxiety

Conclusions

The results of this study established a support for the traditional usage of Carica papaya as anxiolytic medicinal plant.     

赤灵芝孢子粉水溶性提取物(肌生注射液)对小鼠的催眠镇静作用

目的：研究赤灵芝孢子粉水提物（肌生注射液）对小鼠中枢神经系统的作用。方法：以翻正反射消失出现时间作为睡眠时间,观察不同剂量和给药方式下肌生液对小鼠戊巴比妥钠和巴比妥钠睡眠时间及自主活动等的影响。结果：皮下注射肌生液可明显延长小鼠戊巴比妥钠和巴比妥钠睡眠时间,且有剂量效应关系。肌生液亦可诱导注射阈下剂量的戊巴比妥的小鼠入睡。每日注射具有镇静作用剂量的肌生液一次连续8天不产生依赖性,而安定连续给药8天后产生依赖性。肌生液可明显减少小鼠的自主活动。结论：灵芝孢子粉水提物对小鼠中枢神经系统具有镇静催眠的效果。     

Effects of saffron (Crocus sativus L.) and its active constituent, crocin, on recognition and spatial memory after chronic cerebral hypoperfusion in rats

Cerebral ischemia produces brain damage and related behavioral deficits such as memory. In this study, a rat model of chronic cerebral hypoperfusion was used to determine whether saffron extract and crocin, which are potent antioxidants and free radical scavengers, can reduce vascular cognitive impairment. Male adult Wistar rats were administered different doses of an aqueous solution of crocin or hydroalcohol extract of saffron intraperitoneally (i.p.) 5 days after permanent occlusion of the common carotid arteries. Spatial learning and memory were assessed in training trials, 7–11 days after common carotid artery ligation using the Morris water maze. The results showed that the escape latency time was significantly reduced from 24.64 s in the control group to 8.77 and 10.47 s by crocin (25 mg/kg) and saffron extract (250 mg/kg). The traveled distance to find the platform was also changed from 772 cm in the control group to 251 and 294 cm in the crocin (25 mg/kg) and saffron extract (250 mg/kg) groups. The percentages of time spent in the target quadrant, in comparison with the control group (24.16%), increased to 34.25% in the crocin (25 mg/kg) and 34.85% in the saffron extract (250 mg/kg) group. This study suggests that saffron extract and crocin improve spatial cognitive abilities following chronic cerebral hypoperfusion and that these effects may be related to the antioxidant effects of these compounds. Copyright © 2011 John Wiley & Sons, Ltd.     

Assessment of Cytotoxic Properties of Safranal and Nanoliposomal Safranal in Various Cancer Cell Lines

Saffron (Crocus sativus) is a widely used food additive used for its color and taste. It has been reported that saffron possesses significant in vivo and in vitro anti‐tumor activity. In the present study, anti‐tumor effects of safranal, the major aromatic compound in saffron, and its liposomal form were investigated. The role of apoptosis has also been explored in this toxicity. HeLa, MCF7 and L929 cell lines were cultured and exposed to safranal (0.01–3 mM) or liposomal safranal (0.04–0.32 mM). 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium (MTT) assay was performed to assess cytotoxicity. Apoptosis was evaluated by staining cells with propidium iodide and quantifying sub‐Gl peak by flow cytometry. MTT assay revealed a significant and concentration‐dependent cytotoxic effect of safranal on HeLa and MCF7 cell lines. Liposomal safranal showed enhanced effect compared to the safranal solution, as compared by their IC₅₀ concentrations. Flow cytometry results revealed induction of apoptosis by safranal. It might be concluded that safranal could be involved in saffron‐induced cell death in HeLa and MCF7 cells. Liposome encapsulation improved anti‐tumor effect of safranal. Safranal and particularly its liposomal form could be investigated as promising chemotherapeutic agents in cancer treatment. Copyright © 2013 John Wiley & Sons, Ltd.     

Hydroalcohol extract and fractions of Stachys lavandulifolia Vahl: effects on spontaneous motor activity and elevated plus-maze behaviour

The present study aimed to investigate the anxiolytic effects of four fractions of Stachys lavandulifolia Vahl. The aerial parts of the plant were extracted with petroleum ether (PF), ethyl acetate (EF), butanol (BF) and water (AF) and tested for spontaneous motor activity and elevated plus-maze (EPM) behaviour in mice. The hydroalcohol extract (HE) and different fractions of S. lavandulifolia were administered intraperitoneally to male Syrian mice, at various doses, 30 min before the behavioural evaluation. The HE of S. lavandulifolia (at 50 mg/kg) increased the percentage of time spent (39%) and the percentage of arm entries in the open arms (53%). The HE (50 mg/kg), PF (25 and 50 mg/kg), EF (25 and 50 mg/kg) and AF (50 mg/kg) of S. lavandulifolia significantly increased the percentage of time spent and the percentage of arm entries in the open arms. The BF up to a dose of 50 mg/kg had no significant effects on any of the measured parameters in the EPM. The spontaneous locomotor activity was significantly decreased in animals injected with each plant fractions, compared with that of saline. The EF and AF showed the least and the most reduction in the activity, respectively. The anxiolytic effects of EF, PF and AF could be related to their content of flavonoids, phenylpropanoids or terpenoids.     

Anti-inflammatory,analgesic activity and acute toxicity of Glaucium grandiflorum extract

The species of Glaucium have been used in Iranian herbal medicine as laxative, hypnotic, antidiabetic agents and also in the treatment of dermatitis. The anti-inflammatory and analgesic effects of the aerial parts of Glaucium grandiflorum Boiss & Huet (Papaveraceae), a native plant of Iran, were studied using carrageenan induced edema, formalin and hot plate tests. The G. grandiflorum extract at the dose of 200 mg/kg had more edema inhibition than indomethacin at the doses of 10 (P<0.01) and 8 mg/kg (P<0.001) in the carrageenan test. The ED₅₀ (i.p.) in the edema induced by carrageenan was 13.59 mg/kg. In formalin test, the extract (60–90 mg/kg, i.p.) caused graded inhibition of both phases of formalin-induced pain. In hot plate test, the i.p. administration of the extract at the doses of 60, 70, 80 and 90 mg/kg significantly raised the pain threshold at a observation time of 45 min in comparison with control (P<0.001). The extract, at the antinociceptive doses, did not affect motor coordination of animals when assessed in the rotarod model. The 72 h acute LD₅₀ value of this extract after i.p. administration in mice was 797.94 mg/kg.     

Anxiolytic effect of seed of Ziziphus jujuba in mouse models of anxiety

The aim of the present study was to investigate the ethanolic extract of Semen Ziziphi jujuba (SZJE) induced anxiolytic effect. The SZJE was orally administered to male ICR mice, at 0.5, 1.0 and 2. 0 g/kg, 30 min before the behavioral evaluation in the black and white test (BWT) and elevated plus maze (EPM). The SZJE at the dosage 0.5-2.0 g/kg increased the first time entry, total changes and times spent in the white chamber of the BWT. The SZJE at the dosage 0.5-1.0 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 and the percentage of arm entries in the closed arms of the EPM. Furthermore, the SZJE at the dosage of 1. 0 g/kg prolonged the hexobarbital-induced sleeping time in mice and decreased the locomotor activity in rats. These results suggested that SZJE possessed anxiolytic effect at lower dose and sedative effect at higher dose.     

Anxiolytic effects of Stachys lavandulifolia Vahl on the elevated plus-maze model of anxiety in mice

Interest in alternative medicine and plant-derived medications that affect the "mind" is growing. The aim of the present study was to investigate the effects of a hydroalcoholic extract and essential oil of Stachys lavanduifolia Vahl on the elevated plus-maze (EPM) model of anxiety. The Stachys lavandulifolia extract or its essential oil was administered intraperitoneally to male TO mice, at various doses, 30 min before the behavioral evaluation. The extract of Stachys lavandulifolia at the dose of 100 mg/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 and the percentage of arm entries in the closed arms of the EPM. The plant extract at doses lower than 100 mg/kg had no significant effects on any of the parameters measured on the EPM. This dose of the plant extract prolonged the ketamine-induced sleeping time, and decreased the locomotor activity in mice. These results suggested that the extract of Stachys lavandulifolia possessed anxiolytic effect with relatively lower sedative activity than diazepam. The essential oil of Stachys lavandulifolia, however, at doses of up to 100 mg/kg did not have any significant effects on the mice behaviour on the EPM.