Kaempferol from the leaves of Apocynum venetum possesses anxiolytic activities in the elevated plus maze test in mice

The present work evaluated the anxiolytic activity of an aqueous extract of Apocynum venetum L. (Apocynaceae) and bioguided its fractionation using the elevated plus maze (EPM) in mice as a model of anxiety. A single treatment of AV extract markedly increased the percentage time spent on the open arms of the EPM in two distinct concentration ranges of 22.5–30 and 100–125 mg/kg p.o., respectively, indicating a putative anxiolytic-like activity. Fractions showing anxiolytic effects in concentrations equal to 30 or 125 mg/kg of whole extract were antagonized using the benzodiazepine antagonist flumazenil (3 mg/kg i.p.) or the 5-HT_1A receptor antagonist WAY-100635 (0.5 mg/kg i.p.). All active fractions in a concentration equal to 125 mg/kg were effectively blocked by the benzodiazepine antagonist flumazenil, while the anxiolytic activities of fractions in the lower dose equivalent to 30 mg/kg of whole extract were inhibited by the 5-HT_1A receptor antagonist WAY-100635. Through further separation of AV fractions it was possible to isolate and characterize the flavonol kaempferol which showed an anxiolytic-like activity in concentrations from 0.02 to 1.0 mg/kg p.o. The anxiolytic activity of kaempferol was partially antagonized by concomitant administration of flumazenil, but not by WAY-100635. In conclusion, our study clearly demonstrates that AV extract possesses anxiolytic-like activity and that at least one of its flavonoids, kaempferol, can elicit the same kind of neuropharmacological activity.     

Asparagus racemosus Attenuates Anxiety-Like Behavior in Experimental Animal Models

Asparagus racemosus Linn. (AR) is used worldwide as a medicinal plant. In the present study, the anxiolytic activity of standardized methanolic extract of root of AR (MAR) was evaluated in open-field test (OFT), hole-board, and elevated plus maze (EPM) tests. Rats received oral pretreatment of MAR in the doses of 50, 100, and 200 mg/kg daily for 7 days and then were evaluated for the anxiolytic activity in different animal models. Both MAR (100 and 200 mg/kg) and diazepam (1 mg/kg, p.o.) increased the grooming behavior, number of central squares crossed, and time spent in the central area during OFT. Further, MAR (100 and 200 mg/kg) increased the head-dip and head-dip/sniffing behavior, and decreased sniffing activity in hole-board test. Furthermore, MAR (100 and 200 mg/kg) increased the percentage entries and time spent to open arm in EPM test paradigm. The anxiolytic activity in the experimental models was similar to that of diazepam. MAR (100 and 200 mg/kg) enhanced the level of amygdalar serotonin and norepinephrine. It also increased the expression of 5-HT_2A receptors in the amygdala. In another set of experiment, flumazenil attenuated the anxiolytic effect of minimum effective dose of MAR (100 mg/kg) in OFT, hole-board, and EPM tests, indicating GABA_A-mediated mechanism. Moreover, the anxiolytic dose of MAR did not show sedative-like effect in OFT and EPM tests compared to diazepam (6 mg/kg, p.o.). Thus, the anxiolytic response of MAR may involve GABA and serotonergic mechanisms. These preclinical data show that AR can be a potential agent for treatment of anxiety disorders.     

CNS anti-depressant,anxiolytic and analgesic effects of Ganoderma applanatum (mushroom) along with ligand-receptor binding screening provide new insights: Multi-disciplinary approaches

This research was designed to evaluate the CNS depressant, anxiolytic, and analgesic action of aqueous and ethanol extract of Ganoderma applanatum, a valuable medicinal fungus used in multiple disorders belongs to Ganodermataceae family. Two extracts of G. applanatum were prepared using distilled water and ethanol as solvents and named AEGA and EEGA. Open field method, rotarod method, tail suspension method, and hole cross method were utilized for the CNS depressant action. In contrast, elevated plus-maze test and hole board method were utilized for the anxiolytic action. For determining the analgesic potential, acetic acid-induced writhing test, hot plate method, and tail immersion test were used. Besides, molecular docking has been implemented by using Discovery studio 2020, UCSF Chimera and PyRx autodock vina. At both doses (200 and 400 mg/kg) of AEGA and EEGA showed significant CNS depressant effect (p < 0.05 to 0.001) against all four tests used for CNS depressant activity. Both doses of AEGA and EEGA exhibited important anxiolytic activity effect (p < 0.05 to 0.001)against the EPM and hole board test. Both doses of AEGA and EEGA also exhibited a potential analgesic effect (p < 0.05 to 0.001) against all three tests used for analgesic action. In addition, in the molecular docking the compounds obtained the scores of ?5.2 to ?12.8 kcal/mol. Ganoapplanin, sphaeropsidin D and cytosporone C showed the best binding affinity to the selected recptors. It can be concluded that AEGA and EEGA have potential CNS depressant, anxiolytic, and analgesic action, which can be used as a natural antidepressant, anxiolytic, and analgesic source.     

Antidepressant- and anxiolytic-like activities of an oil extract of propolis in rats

PurposePropolis biological effects are mainly attributed to its polyphenolic constituents such as flavonoids and phenolic acids that were recently described in the chemical composition of an extract of propolis obtained with edible vegetal oil (OEP) by our group. The aim of this study was to evaluate the effect of OEP on the behavior of rats.Materials and methodsAn in vivo open field (OF), elevated Plus-maze (EPM), and forced swimming (FS) tests were performed to evaluate locomotor activity, anxiolytic- and antidepressant effects of the extract. Besides, oxidative stress levels were measured in rat blood samples after the behavioral assays by evaluation of the Trolox equivalent antioxidant capacity (TEAC) and nitric oxide levels.ResultsOEP increased locomotion in the OF test (50 mg/kg) and central locomotion and open arm entries in the OF and EPM tests (10–50 mg/kg) and decreased the immobility time in the FS test (10–50 mg/kg). Moreover, OEP reduced nitric oxide levels in response to swim stress induced in rats.ConclusionOEP exerted stimulant, anxiolytic and antidepressant effects on the Central Nervous System and antioxidant activity in rats, highlighting propolis as a potential therapeutic compound for behavior impairment of anxiety and depression.     

Antidepressant effect and pharmacological evaluation of standardized extract of flavonoids from Byrsonima crassifolia

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.     

Effect of GABA-negative preparations on the anxiolytic and sedative effects of diazepam

Experiments on rats have shown that bicuculline (2 mg/kg) and picrotoxin (2 mg/kg) abolish the anxiolytic action of diazepam (2.5 mg/kg). Bicuculline (2 and 4 mg/kg) decreases while picrotoxin transforms the sedative effect of diazepam to the anxiolytic one. Picrotoxin (2 mg/kg) reduces the sedative action of gamma-acetylenic GABA (100 mg/kg) but does not favour the manifestation of its anxiolytic effect. It is suggested that the GABA-ergic mechanisms play an important role in the sedative effect of diazepam.     

Behavioral effects of acute and chronic triazolam treatments in albino rats

Previous behavioral studies on triazolam (TZ), which are small in number, could only speculate about tolerance to the anxiolytic effect of TZ, as the experiments did not cover sufficient time (of 4 to 7 days) for tolerance to develop. Therefore longer time for chronic TZ administration is used. We investigated the effects of TZ on motor activity and exploratory behavior using plus maze and open field. Three experiments were conducted. In the first, five groups of rats were acutely treated with different doses of TZ (0.25 mg/kg-4.0 mg/kg). In the second set of experiments, rats were treated chronically with a single daily dose of TZ (started with 0.25 mg/kg and increased by time to 1.0 mg/kg) for 5 weeks (representing clinical use). In the third, rats were treated chronically with three daily doses of TZ (started with 0.25 mg/kg and increased by time to 0.5 mg/kg) for 20 days (mimicking drug abuse). Acute TZ administration produced dose dependent anxiolytic effects and a decrease in motor activity with higher doses. Chronically treated rats, either once daily or three times daily doses, showed tolerance to both anxiolytic and sedative effects of TZ. It may be concluded that tolerance to the anxiolytic and sedative effects of TZ would develop after chronic administration either with clinical use or its abuse.     

Synthesis and pharmacological evaluation of new arylpiperazines N-{4-[4-(aryl) piperazine-1-yl]-phenyl}-amine derivatives: Putative role of 5-HT1A receptors

In an attempt to design novel 5-HT_1A agonists/partial agonists, based on an arylpiperazine nucleus, a series of N-{4-[4-(aryl)piperazine-1-yl]-phenyl}-amine derivatives were synthesized and biologically tested. The anxiolytic effect of the compounds was investigated employing the Elevated plus Maze (EPM) task. On the basis of in vivo functional test, compound 1c (3 mg/kg) and 4c (3 mg/kg) induced significant increments in open arm entries and time on EPM as compared to Buspirone. The anxiolytic effects of compounds 1c and 4c were effectively antagonized by WAY-100635, a 5-HT_1A receptor antagonist (0.5 mg/kg). Furthermore, we have also evaluated the concentration of 5-HT in the brain tissue using HPLC with fluorescent detection. Our result showed that serotonin levels were significantly decreased by ～38% (p < 0.001) and ～32% (p < 0.001) after acute administration of compounds 1c and 4c, respectively. These findings suggest that the anxiolytic like activity of these new arylpiperazines is mediated via 5-HT_1A receptors in the brain.     

Changes in citrus leaf flavonoid concentrations resulting from blight-induced zinc-deficiency

Increased flavonoid concentrations were found to correlate with the elevated levels of leaf phenolic compounds occurring in blight-induced zinc-deficient citrus. In orange (Citrus sinensis L.) leaves, the increases occurred primarily in hesperidin and diosmin, whereas in grapefruit (C. paradisi Macf.) the largest increases occurred in naringin and rhoifolin. Zinc-deficiency occurring in the blighted citrus leaves appeared to be the important contributing factor to the increased flavonoid content. Although the leaves from trees with blight were typically smaller than leaves from unaffected trees, the increased flavonoid content was not significantly due to a concentration effect. Large differences occurred in the percent increases in concentrations of certain citrus leaf flavonoids. While large increases occurred for a number of flavanone and flavone glycosides, much smaller percent increases occurred for other minor flavone glycosides, and the polymethoxyflavone aglycones. The parallel increases occurring in the concentrations of certain flavone glycosides and their flavanone analogs provide a further indication that flavanone glycosides are precursors in the biosynthesis of flavone glycosides in citrus.     

Apigenin 7-glucoside from Stachys tibetica Vatke and its anxiolytic effect in rats

BackgroundStachys tibetica Vatke (Himalayan or mountain tea) grows abundantly in the tropical and subtropical locations of the world including India, Tibet and China. The traditional healers of Kargil and adjoining areas in Ladakh, Jammu and Kashmir in India use the drug to treat fever, cough, phobias and various mental disorders etc. in the form of a decoction or as a tea. Flavonoids are important components in most herbal teas and play an important role in the management of various brain disorders via mimicking the action of benzodiazepines or through benzodiazepine receptors.Aim of the studyThe present study aimed to isolate flavonoids from S. tibetica and to evaluate their anxiolytic potential in comparison to reference synthetic (diazepam) and natural (apigenin) molecules.Materials and methodsS. tibetica root powder was extracted with 95% methanol for about 72 h using a soxhlet apparatus and the resultant extract was subjected to isolation procedures, resulting in the isolation of apigenin 7-glucoside and characterisation by various physical and spectrometric analyses. Apigenin 7-glucoside was evaluated for anxiolytic activity in rats in comparison with the reference compounds diazepam and apigenin using the elevated plus maze (EPM) model.ResultsPhytochemical investigations of S. tibetica revealed the presence of tannins, phenolics, flavonoids, saponins, glycosides and carbohydrates. A flavonoid glucoside, apigenin 7-glucoside was isolated for the first time from the roots of S. tibetica Vatke. The percentage of time spent and arm entries in the open arms was increased while the arms entries and duration of time spent in closed arms were decreased in the groups treated with apigenin 7-glucoside (which dose). In a similar fashion, diazepam and apigenin also exhibited anxiolytic activity (*p < 0.05, **p < 0.01). Apigenin 7-glucoside significantly decreased the percentage of head dips in EPM. Apigenin 7-glucoside showed anxiolytic potential comparable to the reference drugs apigenin and diazepam.ConclusionApigenin 7-glucoside could be an important molecule for the treatment of anxiety and further studies are required to elucidate its possible mechanism of action.     

Anxiolytic effects of Equisetum arvense Linn. extracts in mice

The petroleum ether (PE), chloroform (CH), ethanol (ETH) and water extracts of E. arvense stems were evaluated for anti-anxiety activity in mice using elevated plus maze model. Ketamine induced hypnosis and actophotometer was used to evaluate sedative effect with various extracts in mice. The results were compared with standard drug diazepam. The ethanolic extract of E. arvense (50 and 100 mg/kg) significantly increased the time-spent and the percentage of the open arm entries in the elevated plus-maze model which was comparable to diazepam. Ethanolic extract (100 mg/kg) prolonged the ketamine-induced total sleeping time and decreased the locomotor activity in mice. The results suggest that the ethanolic extract of E. arvense seems to possess anxiolytic effect with lower sedative activity than that of diazepam. The results could be attributed to the flavonoid content of the ethanolic extract.     

Potential hepatoprotective effects of flavonoids contained in propolis from South Sulawesi against chemotherapy agents

The use of doxorubicin and epirubicin as chemotherapy agent causes side effects such as liver damage due to oxidative stress by reactive oxygen species (ROS) that cause increased of ALT and AST level as liver parameter. One source of natural antioxidants as ROS neutralizer comes from flavonoid that contain in propolis. Most researchers claim that flavonoid can be used to protect the liver. The aim of this study was to test the hepatoprotective effect of flavonoid in propolis from South Sulawesi against doxorubicin and epirubicin. The experiment included male Sprague dawley rats divided into nine groups. The rats received the microcapsule propolis or the quercetin orally for 15 days. The hepatotoxicity was promoted by injection epirubicin and doxorubicin (i.v.) with a cumulative dose of 9 mg/kg. In this study, total polyphenol and flavonoid tests of propolis have been carried out, there were 1.1% polyphenols and 2.7% flavonoids, the antioxidant activity tests showed IC50 value of 9849 ppm and LCMS/MS tests supported the presence of phenolic compounds in propolis from South Sulawesi. Liver parameter was measured and the results showed that the propolis 200 mg/kg group produced the lowest ALT and had potential protective effect against doxorubicin and epirubicin-induced hepatotoxicity.     

Agastache mexicana may produce anxiogenic-like actions in the male rat.

Behavioral effects of a water-soluble extract of Agastache mexicana, a plant with purported anxiolytic actions, were studied in male Wistar rats. In the elevated plus-maze test, various doses of the plant extract (3.0 mg/kg body wt.; 9.0 mg/kg body wt.; 12.0 mg/kg body wt.) administered intraperitoneally (i.p.) decreased the exploration of open arms, showing an anxiogenic-like effect. Agastache mexicana (12 mg/kg body wt.; i.p.) did not change immobility in the forced swimming test (i.e., had no anti-depressant effect) but increased the anti-immobility action of 32.0 mg/kg body wt. (i.p.) of desipramine (i.e., increased the antidepressant-like effect of desipramine). A. mexicana had no effect on exploratory activity in an open field test, indicating that it had no sedative effect at the doses used. It is concluded that effects of the water extract of A. mexicana are more consistent with an anxiogenic-like property than an anxiolytic-like one.     

Flavonoids from Houttuynia cordata attenuate H1N1-induced acute lung injury in mice via inhibition of influenza virus and Toll-like receptor signalling

BackgroundInfluenza virus is one of the most important human pathogens, causing substantial seasonal and pandemic morbidity and mortality. Houttuynia cordata is a traditionally used medicinal plant for the treatment of pneumonia. Flavonoids are one of the major bioactive constituents of Houttuynia cordata.PurposeThis study was designed to investigate the therapeutic effect and mechanism of flavonoid glycosides from H. cordata on influenza A virus (IAV)-induced acute lung injury (ALI) in mice.MethodsFlavonoids from H. cordata (HCF) were extracted from H. cordata and identified by high-performance liquid chromatography. Mice were infected intranasally with influenza virus H1N1 (A/FM/1/47). HCF (50, 100, or 200 mg/kg) or Ribavirin (100 mg/kg, the positive control) were administered intragastrically. Survival rates, life spans, weight losses, lung indexes, histological changes, inflammatory infiltration, and inflammatory markers in the lungs were measured. Lung virus titers and neuraminidase (NA) activities were detected. The expression of Toll-like receptors (TLRs) and levels of NF-κB p65 phosphorylation (NF-κB p65(p)) in the lungs were analysed. The effects of HCF on viral replication and TLR signalling were further evaluated in cells.ResultsHCF contained 78.5% flavonoid glycosides. The contents of rutin, hyperin, isoquercitrin, and quercitrin in HCF were 8.8%, 26.7%, 9.9% and 31.7%. HCF (50, 100 and 200 mg/kg) increased the survival rate and life span of mice infected with the lethal H1N1 virus. In H1N1-induced ALI, mice treated with HCF (50, 100 and 200 mg/kg) showed lesser weight loss and lower lung index than the model group. The lungs of HCF-treated ALI mice presented more intact lung microstructural morphology, milder inflammatory infiltration, and lower levels of monocyte chemotactic protein 1 (MCP-1), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) and malondialdehyde (MDA) than in the model group. Further investigation revealed that HCF exerted antiviral and TLR-inhibitory effects in vivo and in vitro. HCF (50, 100 and 200 mg/kg) reduced lung H1N1 virus titers and inhibited viral NA activity in mice. HCF (100 and 200 mg/kg) elevated the levels of interferon-β in lungs. HCF also decreased the expression of TLR3/4/7 and level of NF-κB p65(p) in lung tissues. In vitro experiments showed that HCF (50, 100 and 200 μg/ml) significantly inhibited viral proliferation and suppressed NA activity. In RAW 264.7 cells, TLR3, TLR4, and TLR7 agonist-stimulated cytokine secretion, NF-κB p65 phosphorylation, and nuclear translocation were constrained by HCF treatment. Furthermore, among the four major flavonoid glycosides in HCF, hyperin and quercitrin inhibited both viral replication and TLR signalling in cells.ConclusionHCF significantly alleviated H1N1-induced ALI in mice, which were associated with its dual antiviral and anti-inflammatory effects via inhibiting influenzal NA activity and TLR signalling. among the four major flavonoid glycosides in HCF, hyperin and quercitrin played key roles in the therapeutic effect of HCF.     

Hypoglycemic effect of the total flavonoid fraction from Folium Eriobotryae

The antidiabetic effect of the total flavonoids fraction from leaves of Eriobotrya japonica (EJF) was evaluated through normal and streptozotocin-induced diabetic mice with graded oral doses of 150, 300, 450 mg/kg for 7 days or 14 days. The result showed that the dose of 300 mg/kg and 450 mg/kg resulted significant hypoglycemic effect on normal mice, the dose of 300 mg/kg induced significant decrease in plasma glucose concentration (PGC), glycosylated serum protein (GSP), total cholesterol (TC) and triglyceride (TG), and significant increase in superoxide dismutase (SOD) activity and serum insulin level in streptozotocin-diabetic mice. These results suggested that EJF has hypoglycemic potential.     

Anxiolytic-like effects of extracts from Albizzia julibrissin bark in the elevated plus-maze in rats

The purpose of the this study was to characterize the putative anxiolytic-like effects of the aqueous extract of Albizzia julibrissin stem bark using the elevated plus maze (EPM) in rats. The water extract of Albizzia julibrissin was orally administered at 10, 50, 100 or 200 mg/kg to adult male SD rats, 1 h before behavioral evaluation in an EPM, respectively. Control rats were treated with an equal volume of saline, and positive control rats buspirone (1 mg/kg). Single or repeated treatment (for 7 days) of the water extract of Albizzia julibrissin (at 100 or 200 mg/kg) significantly increased time-spent and arm entries into the open arms of the EPM, and decreased time-spent and arm entries in the closed arms of the EPM versus saline controls (P < 0.05). However, no changes in the locomotor activity and myorelaxant effect were seen in any group versus the saline control. In addition, the anxiolytic-like effects of Albizzia julibrissin extract were abolished by pindolol (10 mg/kg, i.p), a 5-HT(1A/1B) receptor antagonist. These results suggest that Albizzia julibrissin might proved to be an effective anxiolytic agent, and that it acts via the serotonergic nervous system.     

Evaluation of anxiolytic properties of Gotukola – (Centella asiatica) extracts and asiaticoside in rat behavioral models

The ayurvedic medicinal plant Gotukola (Centella asiatica) was evaluated for its anxiolytic properties. Specifically, this study assessed the effects of: Gotukola plant materials of different genotypic origin; hexane, ethyl acetate and methanol extracts of Gotukola; and asiaticoside, a triterpenic compound isolated from Gotukola. Various paradigms were used to assess the anxiolytic activity, including the elevated plus maze (EPM), open field, social interaction, locomotor activity, punished drinking (Vogel) and novel cage tests. The EPM test revealed that Gotukola, its methanol and ethyl acetate extracts as well as the pure asiaticoside, imparted anxiolytic activity. Furthermore, the asiaticoside did not affect locomotor activity, suggesting these compounds do not have sedative effects in rodents.     

Effect of sophora japonica total flavonoids on pancreas,kidney tissue morphology of streptozotocin-induced diabetic mice model

To observe effect of sophora japonica total flavonoids on pancreas, kidney tissue morphology of streptozotocin-induced diabetic mice model. Mice received tail vein injection of streptozotocin (60 mg/kg) for diabetes modeling. The model mice were divided into five groups, to be respectively fed with high, middle and small doses of sophora japonica total flavonoids solution, metformin solution and saline of the same volume. Another blank control group was set to be fed with saline of the same volume. The mice were administered once a day for 30 consecutive days, to be euthanatized after fasting blood glucose level testing on 30th day with pancreas, kidney taken out for pathological section and microscopic examination. The mice chain streptozotocin diabetes modeling was successful, with significant pathological changes (P < 0.01) in pancreas, kidney. Compared with model group, high, middle and small doses of sophora japonica total flavonoids could significantly alleviate streptozotocin-induced pancreas, kidney damage (P < 0.01). Conclusion: Sophora japonica total flavonoids can effectively alleviate pancreas, kidney injury of streptozotocin-induced diabetic mice model.     

Piplartine, an amide alkaloid from Piper tuberculatum, presents anxiolytic and antidepressant effects in mice

In the present work, we studied the effects of piplartine (PIP), an amide alkaloid isolated from the roots of Piper tuberculatum (Piperaceae), in the elevated plus maze, open field, rota rod, pentylenetetrazole (PTZ)-induced seizures, and forced swimming tests, in mice (Swiss, male, 25 g) to assess anxiolytic, sedative, muscle relaxant, anticonvulsant and antidepressant effects, respectively. Results showed that PIP (50 and 100 mg/kg, i.p.), similarly to diazepam, significantly increased not only the number of entrances (100% and 66%, respectively) but also the time of permanence in the open arms (104% and 199%, respectively), indicating that PIP presents an anxiolytic activity. Both effects were completely blocked by the previous administration of flumazenil what suggests the involvement of benzodiazepine type receptors. In the open field test, although PIP did not alter the number of crossings, it significantly increased grooming (103% and 119%) and rearing (60% and 23%), at the doses of 50 and 100 mg/kg respectively, as compared to controls. However, in the rota rod test, PIP was devoid of effect. Although in the PTZ-induced convulsion test, PIP did not alter the latency time for the onset of the first convulsion, as compared to controls, it significantly reduced in 58% and 60%, respectively, the animal's latency time to death. Furthermore, a significant and dose-dependent decrease in the immobility time, as evaluated by the forced swimming test, was observed after PIP administration (41% and 75% decrease, at the doses of 50 and 100 mg/kg, respectively), suggesting an antidepressant effect, similarly to that observed with imipramine, a classical antidepressant drug used as standard. In conclusion, we showed that PIP presents significant anxiolytic and antidepressant activities, making this drug potentially useful in anxiety and depression.