Evaluation of anxiolytic activity of spray dried powders of two South Brazilian Passiflora species

The Passiflora extracts have been used in folk medicine because of its reputed sedative and anxiolytic properties. The present study aimed to compare the potential anxiolytic activity of two Passiflora spray-dried powders obtained from P. alata and P. edulis, known in Brazil as 'maracujá'. Male adult Swiss rats were treated with 200, 400 and 800 mg/kg of spray-dried powders p.o. and anxiolytic activity was evaluated using the elevated plus-maze test. The spray-dried powders showed anxiolytic activity in doses of 400 and 800 mg/kg. Our results support the potential anxiolytic effect of Passiflora spray-dried powders (P. alata and P. edulis).     

Anxiolytic and sedative activities of Passiflora edulis f. flavicarpa

Aim of the study

Many plants in the genus Passiflora have long been used in traditional folk medicines as a remedy for many neurogenic diseases in many countries. A number of species of the genus was studied about their neuropharmacological activities, but the results were inconsistent. No literature reported neuropharmacological studies on Passiflora edulis f. flavicarpa as yet. The present study was aimed at evaluating the anxiolytic and sedative activities of Passiflora edulis f. flavicarpa.

Materials and methods

Swiss albino mice were used as experimental animals in elevated plus-maze (EPM) test and spontaneous activity (SA) test to assay the behavioral effects of ethanolic extract (EE) of the aerial part of Passiflora edulis f. flavicarpa and its fractions, viz. petrol ether extract (PEE), ethyl acetate extract (EAE), n-BuOH extract (BE) and aqueous extract (AE), together with subfractions of BE, viz. BEF-I, BEF-II, BEF-III, BEF-IV and isoorientin, a flavonoid component isolated from BEF-III.

Results

In the EPM test, single-dose oral administration of EE (300 mg/kg and 400 mg/kg), BE (125 mg/kg and 200 mg/kg), AE (200 mg/kg and 300 mg/kg), BEF-I (200 mg/kg), BEF-II (200 mg/kg), BEF-III (100 mg/kg), or isoorientin (20 mg/kg) resulted in anxiolytic-like effects, but a sedative-like activity was produced at higher doses, such as 300 mg/kg of BE, 200 mg/kg of BEF-III, or 40 mg/kg and 80 mg/kg of isoorientin. The results of the SA test manifested that treatment with 400 mg/kg of EE, 300 mg/kg of BE, or 40 mg/kg and 80 mg/kg of isoorientin compromised motor activity in mice, which are in line with the results of the EPM test.

Conclusions

The aerial part of Passiflora edulis f. flavicarpa was anxiolytic at low dose but sedative at high dose. Flavonoids are important active constituents. Since AE contained little flavonoids, it was conjectured that there were other components responsible for the anxiolytic effect of Passiflora edulis f. flavicarpa besides flavonoids.     

Assessment of Sedative Effects of Passiflora edulis f. flavicarpa and Passiflora alata Extracts in Mice,Measured by Telemetry

Several Passiflora species have been used widely as a folk medicine due to their sedative and anxiolytic activities. In Brazil, a number of native plants of the genus Passiflora exist, but only Passiflora edulis f. flavicarpa (PE) and Passiflora alata (PA) are of commercial value. Thus, the aim of the present study was to investigate the sedative effects of aqueous extracts obtained from the pericarp as well as from the leaves of PE and PA in mice using radiotelemetry. Aqueous extracts from PE and PA were tested for effects on locomotion over 180 min in 300 mg/kg, 600 mg/kg and 1200 mg/kg, in male C57BL/6J mice after oral administration. For validation of the telemetry system, caffeine (negative control) and midazolam (positive control) were used. All tested extracts decreased locomotor activity in a dose‐dependent manner in comparison to the control group. The two lower concentrations of each extract showed the highest decrease in locomotion after 24 min, while 1200 mg/kg had a significant sedative effect already after 18 min. Interestingly, aqueous extracts of PA were more active in comparison to aqueous extracts of PE and the pericarp extracts of both plants showed more pronounced effects on locomotor activity if compared to leaf extracts. In conclusion, the present study represents an innovative, objective approach to measure sedative effects of plant extracts with minimized handling‐related stress and remote data collection. Copyright © 2013 John Wiley & Sons, Ltd.     

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.     

Pharmacological evaluation of the anxiolytic and sedative effects of Tilia americana L. var. mexicana in mice

The anxiolytic and sedative effects of Tilia americana L. var. mexicana (Schltdl.) Hardin inflorescence extracts and its acute toxicity were tested. Sodium pentobarbital (SP)-induced hypnosis potentiation (SPP), as well as ambulatory activity and anti-anxiety response in three different experimental models were evaluated with hexane and methanol extracts in mice. In order to determine the proper timing of assessments and to identify the most active extract, a 100mg/kg dosage of hexane, ethyl acetate and methanol crude extracts were tested on SPP after 15, 30 and 60min of the administration. Then a dose-response curve was made for the hexane (10-1000mg/kg) and methanol (10-300mg/kg) extracts in all experimental models. Both extracts produced a significant and dose-dependent lengthening in the time of SP, with the methanol extract being more potent than the hexane extract at 60min after administration. Moreover, a significant and dose-dependent attenuation in the anxiety-response in the plus-maze test and exploratory cylinder activity, but also a diminution in the ambulatory activity and in the head dipping response were observed resembling the response to diazepam. Acute toxicity was observed with less dose of methanol extract (LD(50)=375mg/kg) in comparison to the hexane extract (LD(50)>2900mg/kg). Results of the present study shows that Tilia americana var. mexicana possesses depressant activity on the CNS similar to the better-studied species of European Tilia and reinforces its use as anxiolytic and sedative in traditional medicine.     

Sedative and anxiolytic efficacy of Tilia americana var. mexicana inflorescences used traditionally by communities of State of Michoacan, Mexico

AIM OF THE STUDY: Increasing demand of herbal products acquired in stores and markets, as well as medicinal plants collected for personal consume are a known modern tendency. In this study, the ethnomedicinal use of Tilia americana var. mexicana inflorescences as sedative and anxiolytic is reinforced by examinating inflorescences used by communities of the State of Michoacan, Mexico. MATERIALS AND METHODS: Experimental mouse models were used to evaluate the sodium pentobarbital (SP)-induced hypnosis potentiation, ambulatory activity, as well as sedative and anti-anxiety responses via oral administration of the aqueous extracts (10, 30 and/or 100 and 300mg/kg). RESULTS: All samples tested produced a lengthening in the time of SP. Moreover, a significant attenuation in the anxiety-response in the plus-maze test and a diminution in both the head dipping response and ambulatory activity were observed resembling the response to diazepam (0.3mg/kg, i.p.). TLC profiles of the samples showed similar pattern of flavonoids; HPLC-DAD exhibited peaks identified as derived of quercetin and kaempferol that may be responsible for the plant activity. CONCLUSIONS: Our results demonstrate that inflorescences of stored specimens obtained from popular local markets show the same effectiveness with regard to sedative and anxiolytic-like actions than freshly collected samples. Since no toxicity was observed through this route of administration (up to 5000mg/kg); therefore, it suggests that this plant is secure when used as tranquilizer in folk medicine.     

Depressant Effects of Salvia divinorum Involve Disruption of Physiological Sleep

Although Salvia divinorum is traditionally known as a ‘mind‐altering’ or psychoactive herb used, among others things, as a tranquilizer, this property has not been validated with regard to its efficacy and safety. The objective of this study is to provide evidence for the sedative effects of S. divinorum and discriminate the nature of the responsible constituents by examining different experimental models. A battery of tests, including the open‐field, hole‐board, exploration cylinder, plus‐maze and sodium pentobarbital‐induced hypnosis potentiation, were used in mice after administration of non‐polar, medium polar and/or polar extracts of the plant (10, 30 and 100 mg/kg). Polysomnographic analysis in rats receiving an active medium polar extract (10 and 100 mg/kg) containing salvinorins was also assessed to study the effects of this plant on sleep architecture. All tested extracts produced significant sedative‐like responses, although those of the medium polar extract were more pronounced in mice. The sedative effect of this latter extract, which contains a mixture of salvinorins, caused fragmented sleep architecture in rats by diminishing rapid eye movement (REM) sleep and increased the quiet awake stage at 10 and 100 mg/kg. Our results provide evidence that S. divinorum exhibits sedative‐like depressant properties that alter physiological sleep architecture. Copyright © 2016 John Wiley & Sons, Ltd.     

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.     

Isolation of jacaranone,a sedative constituent extracted from the flowers of the Mexican tree Ternstroemia pringlei

Ethnopharmacological relevance

Ternstroemia pringlei represents one of the most widely employed and commercially exploited medicinal plant in Mexico, used popularly as a tranquilizer and for the treatment of insomnia.

Aim of the study

To investigate the sedative constituents of the plant through a bio-guided fractionation of extracts derived from calyx and fruits.

Materials and methods

Crude extracts with different polarities (CHCl₃, AcOEt, MeOH, aqueous) were prepared and subjected to chromatographic fractionation, leading to the isolation of the sedative compound (1) from the MeOH crude extract. The identity of 1 was unequivocally established by means of 1D and 2D NMR spectroscopic analysis. The sleeping time induced by sodium pentobarbital and the elevated plus-maze models were performed on mice to determine the sedative and anxiolytic activities, respectively. Bioactivity was also investigated though in vitro GABA release experiments using mice brain slices.

Results

The sedative compound was established as jacaranone (1), and its effect was clearly demonstrated through a dose-dependent response analysis (ED₅₀ = 25 mg/kg mouse weight). When tested in the elevated plus-maze model, none of the extracts from Ternstroemia pringlei displayed anxiolytic activity. GABA release experiments showed that the MeOH and aqueous crude extracts released this neurotransmitter at a ratio of 217 and 179 pmol/g protein, respectively, evidencing the presence of other bioactive constituents in the extracts apart of 1, whose activity was absent in this model.

Conclusions

Although 1 has been isolated and identified in a number of plant species, this is the first time that its sedative effect has been demonstrated. No previous record exists of other sedative compounds having been isolated from Ternstroemia pringlei.     

Anxiolytic effect of Rubus brasilensis in rats and mice

The aim of the present work was to investigate if infuse and ethanolic extracts (aqueous, butanolic and wax fractions) of Rubus brasiliensis Martius (Rosaceae) induce anxiolytic effect. The extracts were administered to male Wistar rats and Swiss mice per oral route, at 50, 100 and 150 mg/kg, 30 min before the behavioral evaluation in the elevated plus maze (EPM). Both infuse and wax ethanolic fraction at the dosage 150 mg/kg, vo, increased the number and the percentage of open arm entries of rats and mice. The aqueous and butanolic fractions, obtained from ethanolic extract, failed to induce anxiolytic effect. The treatment of mice with flumazenil (Ro 15–1788), 1.5, 2.0 and 2.5 mg/kg, i.p., 15-min before the administration of infuse or wax fraction, 150 mg/kg, vo, blocked the infuse or wax fraction-induced anxiolytic effect. The LD₅₀ for the wax fraction was 1000 mg/kg. In conclusion, the infuse and wax ethanolic fraction of R. brasiliensis present anxiolytic effect in rats and mice. In addition, it is suggested that the anxiolytic effect may be attributed at least to one liposoluble principle with low acute toxicity which may be acting as an agonist on GABA_A-benzodiazepine receptor complex.     

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.     

Citrus essential oils inhalation by mice: Behavioral testing,GCMS plasma analysis,corticosterone, and melatonin levels evaluation

The use of orange essential oils (EOs) as a complementary treatment is very common in Brazilian popular culture. The levels of melatonin (MEL) and corticosterone (CORT) hormones were investigated simultaneously, by the Luminex? immunoassay system in mice plasma, after Citrus aurantium and Citrus sinensis EOs inhalation for 30 min. The plasma was analyzed by headspace through gas chromatography coupled to mass spectrometry for investigation of the EO components. Mice were submitted to behavioral testing to research anxiolytic‐like, sedative, and antidepressant‐like effects. The inhalation of atmosphere obtained from vaporization of 10% solution of this Citrus EO separately did not affect MEL or CORT plasma levels; that is, the MEL and CORT levels did not present variation in function of the EO in the schedule used. On the other hand, the imipramine positive control used altered the level of MEL as expected. The EO constituents were detected in plasma at different ratios that is present in inhaled EO. Behavioral tests showed that the inhalation of 10% C. sinensis EO presents an anxiolytic‐like and sedative effect. Thus, C. sinensis EO can be a valuable tool for treatment of the anxiety disturbs, apparently without interference with MEL and CORT physiological levels.     

Antinociceptive,neurobehavioral and antioxidant effects of Eupatorium triplinerve Vahl on rats

Ethnopharmacological relevance

Eupatorium triplinerve Vahl belongs to the Asteraceae family, popularly known as Japana. It is a perennial shrub native to Amazon rainforests of South America. Its leaves are used through infusions, decoctions, baths, and tea. It is largely used in Brazilian folk medicine as sedative, febrifuge, stimulant, tonic and anti-inflammatory.

Aim of the study

The present study evaluated the putative effects of Eupatorium triplinerve on the central nervous system (CNS), including locomotor and anxiety activity, depression-like behavior, and antinociception and oxidative stress.

Materials and methods

Two-month-old male Wistar rats (n=7–10 rats/group) and Swiss male and female mice of the species Mus musculus (n=7–10 per group) were administered with 100 mg/kg, 200 mg/kg, 400 mg/kg, 600 mg/kg, and 800 mg/kg of hydroalcoholic extracts of Eupatorium triplinerve (HEET). The behavioral assays included open-field (OF), elevated Plus-maze (EPM), and forced swimming tests (FS). The antinociceptive activity was verified using chemical (acetic acid and formalin) and thermal (hot plate) models of nociception. The oxidative stress levels were measured in rat blood samples after behavioral assays and Trolox equivalent antioxidant capacity (TEAC), nitric oxide and malondialdehyde (MDA) levels were measured in vivo.

Results

Oral pretreatment with HEET reduced the locomotion in OF test (200–800 mg/kg), increased central locomotion and open arms entries in the OF and EPM tests, respectively (600–800 mg/kg), and decreased the immobility time in the FS (200–800 mg/kg). It also reduced the writhing number evoked by acetic acid injection (200–800 mg/kg) and licking time in the first phase of the formalin test (400–800 mg/kg). In the oxidative stress assays, the extract decreased TEAC, Nitric Oxide and MDA levels in response to swimming stress induced in rats.

Conclusions

These results were indicative for the first time that Eupatorium triplinerve exerted mild sedative, anxiolytic and antidepressive effects on the CNS. Antinociceptive effects not related to opioid system and antioxidant activity were also observed. These results support the ethnopharmacological use of Eupatorium triplinerve in popular medicine.     

Toxicological and cytotoxic evaluation of standardized extracts of Galphimia glauca

Galphimia glauca Cav (Malpighiaceae) has been widely used in Mexican traditional medicine as a remedy for the treatment of mental disorders, principally as a sedative and tranquilizer. The sedative activity of extracts obtained from this plant has been demonstrated with different neuropharmacological models. Different triterpenes, known as galphimines, have been identified from the active extract. Galphimine-B (G-B) possesses anxiolytic activity and is able to selectively inhibit discharges of dopaminergic neurons in the ventral tegmental area in rats. Nevertheless, there have been no toxicological investigations carried out with products obtained from this plant. In this work three different extracts (aqueous, ethanolic, and methanolic) of Galphimia glauca, standardized in the content of three galphimines, were evaluated for their behavioral and pharmaco-toxicological effects. After administering the extracts to mice for 28 days (2.5g/kg, p.o.), no deaths were found and the histopathological analysis of different organs did not show alterations; only the behavioral parameters analyzed showed a diminution of spontaneous activity. The administration of these extracts for 56 days (same doses and route) in mice did not cause any changes in the biochemical parameters that evaluate liver function. On the other hand, no cytotoxic effects were found on KB, UISO, and OVCAR-5 transformed cell lines, but all extracts specifically inhibited colon cancer cell line growth with an ED(50) lower than 2microg/ml. The extracts were also evaluated in genotoxicity tests in vitro (250, 100 and 50microg/ml), which demonstrate that none of the three extracts from Galphimia glauca showed a genotoxic effect.     

Antiinflammatory activities of Hungarian Stachys species and their iridoids

The antiinflammatory activities of aqueous extracts prepared from the aerial parts of ten Hungarian Stachys species were investigated in vivo in the carrageenan-induced paw oedema test after intraperitoneal and oral administration to rats. Some of the extracts were found to display significant antiphlogistic effects when administered intraperitoneally and orally; in particular, the extracts of S. alpina, S. germanica, S. officinalis and S. recta demonstrated high activity following intraperitoneal administration. At the same dose of 5.0 mg/kg, these extracts exhibited similar or greater potency than that of the positive control diclofenac-Na. The main iridoids present in the investigated extracts, ajugoside, aucubin, acetylharpagide, harpagide and harpagoside, were also assayed in the same test, and high dose-dependent antiphlogistic effects were recorded for aucubin and harpagoside. These results led to the conclusion that most probably iridoids are responsible for the antiinflammatory effect of Stachys species, but other active constituents or their synergism must also be implicated in the antiinflammatory effect.     

CNS activities of liquid and spray-dried extracts from Lippia alba-Verbenaceae (Brazilian false melissa)

The CNS activity of Lippia alba liquid and spray-dried extracts, containing the non-volatile fraction from the leaves, was investigated. L. alba liquid extracts were prepared by percolation with EtOH 40, 60 or 80%. The liquid extracts, named ES(40%,) ES(60%) and ES(80%,) were concentrated, the ethanol eliminated and then tested in Swiss mice to evaluate its sedative and anticonvulsant effects. The animals received the extracts, orally, in doses corresponding to 200 mg of dry residue by kilogram of body weight. All mice were evaluated in the barbiturate-induced sleep test. Similarly, other groups of mice were submitted to convulsions induced by pentylenetetrazol (PTZ). The concentrated extract obtained from ES(80%) showed the most significant sedative and myorelaxant effects as well as the highest total flavonoid content (66 mg/100 g, expressed in apigenin). Two spray-dried powders, SDP(1) and SDP(2), were prepared from ES(80%) using as excipients, respectively, colloidal silicon dioxide (CSD) and CSD associated to beta-cyclodextrin. Only SDP(1) showed sedative profile similar to that presented by ES(80). In conclusion, we demonstrated that the non-volatile fraction of L. alba, extracted in ethanol 80% (v/v), presents sedative and myorelaxant effects and that, among the tested extracts, this presents the highest flavonoid content. We demonstrated also the technological feasibility of spray-dried extracts and the influence of the excipient on its sedative properties.     

Anti-anxiety activity of successive extracts of angelica archangelica linn.on the elevated t-maze and forced swimming tests in rats

Objective

Angelica archangelica Linn. is widely used in food and liquor preparations and also in Kashmiri folk medicine to reduce anxiety. We evaluated the anxiolytic effect of successive extracts of A. archangelica linn. (SAE) on rats tested in the elevated T-maze test (an animal model of generalized anxiety) at doses that exhibit antidepressant-like activity in humans.

Methods

A. archangelica (1 kg) was subjected to successive extraction in a soxhlet apparatus with solvents [petroleum ether (40–60° C), chloroform, ethyl acetate, methanol and decoction with water] in order of increasing polarity (yield: 6.9%, 7.3%, 5.1%, 11.88% and 8.2% w/w, respectively). SAE were evaluated for anxiolytic effects using the elevated T-maze and forced swimming tests in rats.

Results

Oral dosing of diazepam (1 mg/kg) and extracts (50, 100 and 200 mg/kg) clearly showed an anxiolytic-like profile in the elevated T-maze test: it increased one-way escape and decreased inhibitory avoidance on the first, third and seventh day. In the forced swimming test, imipramine and SAE showed antidepressant- and anxiolytic-like effects as reflected by increased climbing time, swimming time and decreased immobility time on the first, third and seventh day. Aqueous and methanol extracts showed the most, petroleum ether (40–60°C) and chloroform intermediate, and ethyl acetate the least anxiolytic activity (*P<0.05, **P<0.01, ***P< 0.001) in both models.

Conclusions

These results suggest the anti-anxiety activity of various extracts of A. archangelica and strongly justify its use in traditional Indian medicine for the treatment of anxiety.     

Reproductive toxicity potentials of Salvia fruticosa (Labiatae) in rats

The antiimplantation, antifertility and reproductive toxicity potentials after ingestion of aqueous and ethanolic extracts of Salvia fruticosa leaves have been investigated in male and female rats. The ingestion of 200, 400 and 800 mg/kg of aqueous or 400 mg/kg of ethanolic extracts of S. fruticosa from day one to day six of pregnancy by female rats did not cause pregnancy failure. However, the ingestion of an ethanolic extract reduced the number of viable fetuses and increased the number of resorptions in the pregnant rats. The ingestion of aqueous extract (800 mg/kg) or ethanolic extract (400 mg/kg) of S. fruticosa for 30 consecutive days by adult female rats had no effect on the occurrence of pregnancy. However, the ingestion of these extracts reduced both the number of implantations and viable fetuses and increased the number of resorptions in the pregnant females. The ingestion of aqueous extract (800 mg/kg) or ethanolic extract (400 mg/kg) of S. fruticosa for 30 consecutive days by adult male rats had no effect on the number of females impregnated by these males. However, the number of implantations and viable fetuses were reduced in females impregnated by males which ingested either aqueous or ethanolic extracts of S. fruticosa, whereas the number of resorptions was increased in females impregnated by males administered either aqueous or ethanolic extracts of S. fruticosa. On the other hand, the prenatal exposure of male and female rat offspring to 400 mg/kg ethanolic extract of S. fruticosa had no effects on the timing of testicular descent and vaginal opening, respectively. It would appear from these experiments that the ingestion of S. fruticosa may produce adverse effects on the fertility of male and female rats.     

Passiflora incarnata L. Improves Spatial Memory,Reduces Stress,and Affects Neurotransmission in Rats

Passiflora incarnata L. has been used as a medicinal plant in South America and Europe since the 16th century. Previous pharmacological studies focused mainly on the plant's sedative, anxiolytic, and anticonvulsant effects on the central nervous system and its supporting role in the treatment of addiction. The aim of the present study was to evaluate the behavioral and neurochemical effects of long‐term oral administration of P. incarnata. The passionflower extract (30, 100, or 300 mg/kg body weight/day) was given to 4‐week‐old male Wistar rats via their drinking water. Tests were conducted after 7 weeks of treatment. Spatial memory was assessed in a water maze, and the levels of amino acids, monoamines, and their metabolites were evaluated in select brain regions by high performance liquid chromatography (HPLC). We observed reduced anxiety and dose‐dependent improvement of memory in rats given passionflower compared to the control group. In addition, hippocampal glutamic acid and cortical serotonin content were depleted, with increased levels of metabolites and increased turnover. Thus, our results partially confirmed the proposed mechanism of action of P. incarnata involving GABA_A receptors. Copyright © 2016 John Wiley & Sons, Ltd.