Salvia triloba, traditionally known as Greek sage, has been used to enhance memory, as a sedative and to treat headaches. Pharmacological evaluation of purified extracts and isolated compounds of S. triloba were carri...Salvia triloba, traditionally known as Greek sage, has been used to enhance memory, as a sedative and to treat headaches. Pharmacological evaluation of purified extracts and isolated compounds of S. triloba were carried out on functional assays using two-electrode voltage clamp methods on recombinant GABA receptors expressed in Xenopus laevis oocytes. Bio-assay guided fractionation led to seven compounds being isolated from S. triloba: ursolic acid, carnosol, oleanolic acid, salvigenin, rosmanol, cirsimaritin and hispidulin. The purified extracts of S. triloba inhibited 54% of the current produced by 300 μM GABA at α1β2γ2L GABAA receptors. Ursolic acid, carnosol, oleanolic acid and rosmanol also acted as negative allosteric modulators. The flavonoids salvigenin, cirsimaritin and hispidulin acted as positive modulators when applied in the presence of low concentrations of GABA but in the presence of high concentrations of GABA acted as negative modulators, demonstrating a biphasic action. These results are consistent with the concept that Salvia triloba may have cognition enhancing properties. In most cases these activities are likely to be occurring via different modulatory sites on GABAA receptor complexes. It may be that the combination of these activities permits cognition enhancement whilst offering protection from convulsant activity.展开更多
Natural regulatory peptides are biologically active compounds that are produced by various cells and provide a link among the main regulatory systems of the body. The field of research into the biologic activity of en...Natural regulatory peptides are biologically active compounds that are produced by various cells and provide a link among the main regulatory systems of the body. The field of research into the biologic activity of endogenous regulatory peptides is extremely vast. These peptides affect the cardiovascular, immune, reproductive, endocrine, digestive, and other systems, alter energy metabolism, and are especially effective in the regulation of the central nervous system. Despite of the wide range of preventive and therapeutic effects of natural regulatory peptides and proteins, their application in clinical practice is difficult. This is primarily because of their extreme instability, as they are rapidly degraded by proteases of the gastrointestinal tract, blood, cerebrospinal fluid, and other biologic media. Compounds with higher stability (i.e., a considerably longer half-life compared with that of natural molecules) and the ability to provide a directional effect on the various body systems were obtained from modifications of endogenous regulatory peptides. Synthetic analogs of regulatory peptides, as a rule, contain only natural amino acids in their composition, and their biodegradation does not lead to the formation of toxic products;thus, they have fewer side effects. This review focuses on the consideration of two synthetic regulatory peptides, Semax and Selank, which were the bases for the creation of new drugs that are used effectively in the treatment of various diseases of the nervous system. The synthetic analog of an adrenocorticotropic hormone 4-10 fragment (ACTH4-10) Semax is a powerful neuroprotective agent that is particularly effective as a therapy for stroke. Selank was synthesized on the basis of the natural immunomodulator tuftsin. Selank is a powerful anxiolytic that is used as a therapy for generalized anxiety disorder and neurasthenia without sedative and muscle-relaxant effects. This review presents the results of research aimed at studying the influence of these peptides on the transcriptome of brain cells. The problems of drugs developed based on the clinical activities of Semax and Selank are discussed separately.展开更多
Anxiety is a significant mental health issue that substantially affects an individual’s quality of life. Feelings of uneasiness, irritability, and sleep disturbances characterize it. 4-Hydroxyphenyl acetic acid (4-HP...Anxiety is a significant mental health issue that substantially affects an individual’s quality of life. Feelings of uneasiness, irritability, and sleep disturbances characterize it. 4-Hydroxyphenyl acetic acid (4-HPAA) is identified in brain cells as a physiological byproduct of tyramine. This study hypothesizes that 4-HPAA may regulate anxiety due to its anxiolytic properties, acting as a modulator of the GABAergic system, which plays a crucial role in the pathophysiology of anxiety disorders. Our study aims to enhance the anxiolytic effects of 4-HPAA through chemical modification to improve its pharmacokinetic properties. Three derivatives, namely Isopropyl-4-hydroxy-[phenyl] acetate (IHPA), Isopropyl-4-hydroxy-[phenyl] acetate (MPAA), and 4-methoxyphenyl acetate (MPHA), have been synthesized from 4-HPAA. This assessment will use well-established animal models, specifically the Elevated Plus-Maze (EPM) and Zero Maze (EZM) tests, selected for their validity in replicating anxiety-like symptoms in animals. Chronic caffeine administration via drinking water (0.3 g/l for 14 days) was employed to induce an anxiety state for testing purposes. IHPA and MPAA demonstrated significant anxiolyticactivity when tested in the EPM and EZM experiments. Molecular docking simulations using AutoDock Vina indicated that 4-HPAA derivatives had docking scores ranging from −5.8 to −4.8 kcal/mol, compared to the standard anxiolytic medication Diazepam, which scored −7.1 kcal/mol. These scores suggest a potential for 4-HPAA derivatives to interact effectively with the Gamma-aminobutyric acid (GABA_A) receptor. In conclusion, our in vivo and in silico analyses indicate a promising anxiolytic potential for 4-HPAA derivatives.展开更多
Objective:To investigate the anxiolytic activity of newly isolated compound by our lab called ursolic acid stearoyl glucoside(UASG) from the leaves of Lantana camam(L camam).Methods: Column chromatography was used to ...Objective:To investigate the anxiolytic activity of newly isolated compound by our lab called ursolic acid stearoyl glucoside(UASG) from the leaves of Lantana camam(L camam).Methods: Column chromatography was used to isolate UASG.Anxiolytic potential was experimentally proved and demonstrated through Elevated plus-maze,Open field and light and dark test. Results:The UASG showed marked increased in time spent(%) and number of frequent movements made by animals in open arm of elevated plus-maze apparatus.In light and dark model,UASG produced marked increase in time spent by animal,number of crossing and reduced duration of immobility in light box.Conclusions:UASG showed significant increase in number of rearing,assisted rearing and number of square crossed in open field established test model.UASG showed its anxiolytic effect in dose dependent manner.展开更多
Globally,the prevalence of anxiety and depression has reached epidemic proportions.Food-derived protein hydrolysates and peptides delivered through dietary supplementation can avoid the negative risks associated with ...Globally,the prevalence of anxiety and depression has reached epidemic proportions.Food-derived protein hydrolysates and peptides delivered through dietary supplementation can avoid the negative risks associated with traditional pharmaceuticals while delivering superior anxiolytic and antidepressant effects.This review summarizes current research on food-derived anxiolytic and antidepressant protein hydrolysates and peptides,and subsequently analyses their physicochemical characteristics and elaborates on their mechanisms.The aim of this work is to contribute to the in-depth study and provide a theoretical foundation for the development of related products to better serve patients with anxiety and depression.展开更多
Social defeat stress(SDS)plays a major role in the pathogenesis of psychiatric disorders like anxiety and depression.Sleep is generally considered to involve recovery of the brain from prior experience during wakefuln...Social defeat stress(SDS)plays a major role in the pathogenesis of psychiatric disorders like anxiety and depression.Sleep is generally considered to involve recovery of the brain from prior experience during wakefulness and is altered after acute SDS.However,the effect of acute SDS on sleep/wake behavior in mice varies between studies.In addition,whether sleep changes in response to stress contribute to anxiety is not well established.Here,we first investigated the effects of acute SDS on sleep/wake states in the active period in mice.Our results showed that total sleep time(time in rapid eyemovement[REM]and non-REM[NREM]sleep)increased in the active period after acute SDS.NREM sleep increased mainly during the first 3 h after SDS,while REM sleep increased at a later time.Then,we demonstrated that the increased NREM sleep had an anxiolytic benefit in acute SDS.Mice deprived of sleep for 1 h or 3 h after acute SDS remained in a highly anxious state,while in mice with ad libitum sleep the anxiety rapidly faded away.Altogether,our findings suggest an anxiolytic effect of NREM sleep,and indicate a potential therapeutic strategy for anxiety.展开更多
Objective:To research the acute toxicity of Illicium verum(I.verum)fruit extracts and its action on central nervous system.Methods:The TLC and HPTLC techniques were used as fingerprints to determine the chemical compo...Objective:To research the acute toxicity of Illicium verum(I.verum)fruit extracts and its action on central nervous system.Methods:The TLC and HPTLC techniques were used as fingerprints to determine the chemical components present in I.verum.Male albino rats and mice were utilized for study.The powdered material was successively extracted with n-hexane,ethyl acetate and methanol using a Soxhlet extractor.Acute toxicity studies were performed as per OECD guidelines.The CNS activity was evaluated on parameters of general behavior,sleeping pattern,locomotor activity,anxicty and myocoordination activity.The animals were trained for seven days prior to experiments and the divided into five groups with six animals in each.The drug was administered by intraperitoneal route according to body weight.The dosing was done as prescribed in each protocol.Results:Toxicity studies reported 2 000 mg/kg as toxicological dose and 1/10 of the same dose was taken as therapeutic dose Intraperitoneal injection of all extracts at dose of 200 mg prolonged phenobarbitone induced sleeping time,produced alteration in general behavior pattern,reduced locomotor activity and produced anxiolytic effects but the extracts do not significantly alter muscles coordination activity.The three extracts of I.verum at the dose of 200 mg,methanol extract was found to produce more prominent effects,then hexane and ethylacetate extracts.Conclusions:The observation suggested that the extracts of I. verum possess potent CNS depressant action and anxiolytic effect without interfering with motor coordination.展开更多
Objective: To evaluate the neuropharmacological properties of Costus speciosus(C. speciosus) rhizome using different experimental mouse models. Methods: The anxiolytic effect was investigated by hole-board test, eleva...Objective: To evaluate the neuropharmacological properties of Costus speciosus(C. speciosus) rhizome using different experimental mouse models. Methods: The anxiolytic effect was investigated by hole-board test, elevated plus maze and light/dark test, while central nervous system(CNS) depressant effect was evaluated by thiopental sodium-induced sleep test. Finally, antidepressant effect was evaluated by forced swimming test and tail suspension test. Results: In both elevated plus maze and hole board test, 400 mg/kg C. speciosus showed more significant CNS depressant effect than 1 mg/kg diazepam. Both 200 mg/kg and 400 mg/kg C. speciosus extract produced a significant dose-dependent decrease in onset of sleep. In forced swimming test, C. speciosus rhizome showed a decrease in duration of immobility in a dose-dependent manner. Imipramine(10 mg/kg) and C. speciosus extract at 400 mg/kg dose exhibited a significant reduction in duration of immobility in tail suspension test which provided additional evidence of antidepressant effect of C. speciosus rhizome. Conclusions: Our study indicates that C. speciosus rhizome possesses CNS depressant, anxiolytic and antidepressant-like activities. Further studies are warranted determine the exact phytoconstituents and mechanism of action responsible for the neuropharmacological effect.展开更多
Objective: To elucidate the anxiolytic and free radical scavenging effect of methanolic extract of Apium graveolens(A. graveolens) in adult C57BL/6 mice.Methods: Sixty male mice were divided into 6 groups: control, ve...Objective: To elucidate the anxiolytic and free radical scavenging effect of methanolic extract of Apium graveolens(A. graveolens) in adult C57BL/6 mice.Methods: Sixty male mice were divided into 6 groups: control, vehicle, positive control and A. graveolens(125, 250 and 500 mg/kg). Different behavioral models of elevated plus maze, open field, light/dark, hole-board and pentobarbital-induced sleep were used to assess anxiety-like behavior. Biochemical parameters including monoamine oxidase-A(MAO-A) activity, lipid peroxidation, % inhibition of superoxide anion and glutathione peroxidase activity were measured. Histologic studies were also examined.Results: Mice receiving various doses of A. graveolens(125, 250 and 500 mg/kg)showed an alleviation of anxiety-like behavior as evidenced by the battery of behavioral tests. Likewise, A. graveolens treatment was found to significantly decrease MAO-A activity, lipid peroxidation as well as cause a significant increase of % inhibition of superoxide anion and glutathione peroxidase activity in both cortex and striatum. The total number of survival neurons found in the frontal cortex and striatum was significantly higher than that of the vehicle-treated group.Conclusions: Taken together, we showed that A. graveolens improve the behavioral changes which might be related to the inhibition of free radicals and modulation of MAOA activity resulting in an increased number of survival neurons. Our findings suggest the therapeutic potential of A. graveolens in the treatment of anxiety.展开更多
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...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℃),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℃) 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.展开更多
Anxiety is an unpleasant state,which can critically decrease the quality of life is often accompanied by nervous behaviour and rumination.Niranthin is a lignan isolated from various Phyllanthus sources.The literature ...Anxiety is an unpleasant state,which can critically decrease the quality of life is often accompanied by nervous behaviour and rumination.Niranthin is a lignan isolated from various Phyllanthus sources.The literature survey on niranthin highlights wide ranges of the therapeutic potentials.In a present study,based on our previous investigations,we evaluated pure,isolated and characterized niranthin as an anxiolytic agent.The niranthin[6-[(2R,3R)-3-[(3,4-dimethoxyphenyl)methyl]-4-methoxy-2-(methoxymethyl)butyl]-4-methoxy-1,3-benzodioxole]was purchased from commercial source and further subjected for assessment of its anxiolytic potentials using popular animal models including Elevated plus-maze model/test(EPM)and Light&Dark Exploration test(L&D).GABA-A receptor mediation was evaluated by pretreating the mice with the GABA-A receptor antagonist Flumazenil before the EPM task.Molecular docking simulation studies(pdb id:4COF)carried out by Vlife QSAR software showed that niranthin(docking score:−62.1714 kcal/mol)have shown comparatively best docking score compared to the standard drug Diazepam(docking score:−63.1568 kcal/mol).To conclude,Niranthin has probable potential in the management of anxiety disorder.Our in-silico and in-vivo analysis(indirectly)indicated the plausible role of GABA mediation for anxiolytic activity.Although,these studies are preliminary,future in depth experimental explorations will be required to use Niranthin as anti-anxiety drug in near future.展开更多
Objective:To clarify the neuropharmacological profile of the Mongolian vetch,Astragalus mongholicus(Astragalus membranaceous var.mongholicus;synonym:A.mongholicus),extracts were evaluated for behavioral effects in rat...Objective:To clarify the neuropharmacological profile of the Mongolian vetch,Astragalus mongholicus(Astragalus membranaceous var.mongholicus;synonym:A.mongholicus),extracts were evaluated for behavioral effects in rats and mice.Methods:An aqueous extract of A.mongholicus was made by boiling roots from freshlycollected plants in 2.5 volumes(w/v)of water for 60 minutes.An ethanol extract was made by incubating in 70%ethanol for 5 days at 25C.Effects of the aqueous extracts were evaluated in a forced swimming assessment of antidepressant effects,a hole-board test of exploratory behavior,an analysis of inhibition of aggression following electrical stimulation and influences on amnesia resulting from electroshock.Furthermore,effects of ethanol extracts of A.mongholicus were assessed on L-tryptophan induced twitches(indicating serotonin-mediated effects)and on hypothermia induced by apomorphine(indicating dopamine-mediated interactions)in mice.Results:Per os(PO)administration of the aqueous decoction of the vetch to rats increased the response in a forced swimming test as reflected in wheel rotations.However,the decoction had no significant effect on the exploratory behavior of rats in the hole-board test.Acute PO administration of the aqueous extract of A.mongholicus decreased the threshold for aggressive behavior and this effect persisted with subchronic administration.Chronic administration of the plant extract suppressed aggression of rats.An ethanol extract of A.mongholicus showed an antiserotoninergic action and had a significant influence on the hypothermia induced by apomorphine.Conclusion:A.mongholicus has a variety of potent psychotropic actions,suggesting influences on diverse neurotransmitter systems.展开更多
In recent years,there has not been much progress in developing anxiolytic drugs.Amongst the barriers are the lack of clarity on the pathogenesis of anxiety disorders,low product conversion rates for developing drugs t...In recent years,there has not been much progress in developing anxiolytic drugs.Amongst the barriers are the lack of clarity on the pathogenesis of anxiety disorders,low product conversion rates for developing drugs targeting the receptors,and species variability.Some scientists have focused on natural medicines,especially herbal medicines in traditional Chinese medicine.New drugs with excellent anxiolytic activity are hoped to be found in herbal medicines with anxiolytic effects.This mini-review summarised three Chinese herbal medicines with anxiolytic effects and anxiolytic herbal formulas used in the traditional Chinese medicine clinic.Several key issues that block the development of new anxiolytic drugs are also discussed.We hope to provide some ideas for researching and developing new anxiolytic drugs and studying anxiolytic components in traditional Chinese medicine.展开更多
Objective:To analyze in vivo neuro-pharmacological effects of Alpinia nigra as anxiety is a particular form of behavioral inhibition that occurs in response to novel environmental events.Methods:In present study,the e...Objective:To analyze in vivo neuro-pharmacological effects of Alpinia nigra as anxiety is a particular form of behavioral inhibition that occurs in response to novel environmental events.Methods:In present study,the extract of Alpinia nigra was evaluated for its central nervous system depressant effect using mice behavioral models,such as hole cross,open field and thiopental sodium induced sleeping time tests for its sedative properties and an elevated plusmaze test for its anxiolytic potential,respectively.Results:In anxiolytic study,the extract displayed increased percentage of entry into open arm ut the dose of 400 and 200 mg/kg.The extract produced a significant(P<0.01) increase in sleeping duration and reduction of onset of sleep compared to sodium thiopental at both doses(200 and400 mg/kg).The extract t.200 and 400 mg/kg) also showed a dose-dependent suppression of motor activity and exploratory activity of the mice in both open field and hole cross test.Conclusion:This study demonstrates that the treated extract has significant central nervous system depressant effect.Further studies on active constituent of the extract can provide approaches for therapeutic intervention.展开更多
OBJECTIVE To investigate the relationship between the neurochemical and behavioral effects of inhibitors of cyclic nucleotide phosphodiesterases 2(PDE2) and PDE4 in the hope of identifying promising therapeutic target...OBJECTIVE To investigate the relationship between the neurochemical and behavioral effects of inhibitors of cyclic nucleotide phosphodiesterases 2(PDE2) and PDE4 in the hope of identifying promising therapeutic targets and indications. METHODS Depression-and anxiety-like behaviors were evaluated by forced swimming,tail suspending and elevated plus maze tests. The memory enhancing effects were evaluated by Morris water maze test. RESULTS Inhibition of PDE4 results in antidepressant-like and memory-enhancing effects,in part due to increased cyclicAMP signaling.While targeting PDE4 subtypes(PDE4A-D) pharmacologically has proven challenging due to a highly conserved inhibitor-binding site in the catalytic region of the enzyme,some promise is offered by recently identified negative allosteric modulators of PDE4,which can act in a subtype-specific manner.While PDE2 has not been studied as extensively,it has been shown to be coded for by a single mammalian gene and to be highly expressed in the brain. Its inhibition results in anxiolytic-and antidepressant-like effects as wells as reducing oxidative stress and affording some degree of neuroprotection;these actions appear to be due to increased cyclicGMP signaling,even though PDE2 catalyzes the hydrolysis of both cyclicAMP and cyclicGMP. CONCLUSION Inhibitors targeting specific family of PDE may exhibit differential pharmacological effects and aid a more efficient pharmacotherapy towards neuropsychological conditions,while drug discovery efforts focusing on PDE2 are not as advanced as those for PDE4,some selective inhibitors are being developed and evaluated.展开更多
We investigated the effects of a standardized extract of Caralluma fimbriata Wall (CFE) on learning and memory in mice using various behavioural models. Unusually, CFE exerts both nootropic and anxiolytic effects.
In indigenous or folk medicine, Euphorbia hirta is a very popular herb and used as a palliative to treat various ailments including intestinal parasites, diarrhoea, vomiting, amoebic dysentery, asthma, bronchitis, emp...In indigenous or folk medicine, Euphorbia hirta is a very popular herb and used as a palliative to treat various ailments including intestinal parasites, diarrhoea, vomiting, amoebic dysentery, asthma, bronchitis, emphysema, coughs, kidney stones, menstrual problems etc. The objective of this study is to evaluate the anxiolytic and sedative-like effects of the methanol extract from the leaves of Euphorbia hirta (Euphorbiaceae). Methanolic extract of Euphorbia hirta was evaluated for its CNS depression effect using mice behavioral models such as, elevated plus maze and hole board test for its anxiolytic potential where hole cross and pentobarbital-induced sleeping time tests were performed for its sedative properties, respectively. The test group received three different doses of the MEHL (100 mg/kg, 200 mg/kg and 300 mg/kg) orally. The positive control group received diazepam (1 mg/kg) orally where the negative control group received distilled water (10 ml/kg) orally. In elevated plus maze test, the extract exhibited significant (p d the number of open arm entry and time spent in open arm by mice compared to control group. In addition, the number of head dips and hole crosses significantly (p < 0.05) decreased by mice in hole board and hole cross tests respectively, compared to control group. Moreover, mice treated with MEHL significantly decrease the onset of sleep and increase the duration of sleep in pentobarbital-induced sleeping time test in mice compared to control group. The data obtained from the present study clearly demonstrate that the methanolic extract of Euphorbia hirta has potential anxiolytic and sedative-like activity in the animal behavioral models. And the findings represent a rational explanation for its use in traditional medicine for the management of neurological disorder.展开更多
Formononetin is an isoflavone phytoestrogen mainly existing in leguminous plants such as Trifolium pretense,Spatholobus suberectus,etc.Studies have proved that formononetin has good anti-inflammatory,antitumor,antioxi...Formononetin is an isoflavone phytoestrogen mainly existing in leguminous plants such as Trifolium pretense,Spatholobus suberectus,etc.Studies have proved that formononetin has good anti-inflammatory,antitumor,antioxidant,antidepressant,anxiolytic and other pharmacological effects.This paper summarizes the pharmacological action and molecular mechanism of formononetin,in order to provide a theoretical basis for the development and clinical application of formononetin.展开更多
Bacopa monniera Linn. or Brahmi, a plant in the family Scrophulariaceae, is used as a traditional medicine for memory improvement, dementia like anxiety, depression, epilepsy etc. for a long time in Bangladesh. This s...Bacopa monniera Linn. or Brahmi, a plant in the family Scrophulariaceae, is used as a traditional medicine for memory improvement, dementia like anxiety, depression, epilepsy etc. for a long time in Bangladesh. This study evaluated the anxiolytic effects of the methanolic extract of B. monniera (MEBM) in animal models of anxiety. For the further tests and phytochemical screening, the whole plant of B. monniera extracted following maceration method. The extract was evaluated for anxiolytic activity using light/dark box, elevated plus maze, marble burying and rota rod tests in mice at the doses of 50, 100, and 200 mg/kg body weight. Diazepam (1.0 mg/kg), an anxiolytic drug used as standard drug. MEBM showed a strong and dose-dependent anxiolytic effects in animal models of anxiety. MEBM significantly increased the time spent in the light compartment, the latency time, and the entries of open arms in light/dark and elevated plus maze tests. In addition, MEBM also significantly decreased the number of buried marbles in marble burying test and increased the time of performance in rota rod test (p < 0.05). These were the major findings of this study. Therefore, our results reported that MEBM possesses anxiolytic effects in animal models of anxiety that support the traditional use of this plant as a potent agent to combat anxiety.展开更多
Koumine is an indole alkaloid monomer extracted from the Chinese herb Gelsemium elegans,which has a variety of pharmacological effects.This paper provides a comprehensive summary of the pharmacological effects and mol...Koumine is an indole alkaloid monomer extracted from the Chinese herb Gelsemium elegans,which has a variety of pharmacological effects.This paper provides a comprehensive summary of the pharmacological effects and molecular mechanisms of koumine,with a particular emphasis on its mechanisms of action in the context of anticancer,anti-inflammatory,analgesic,and anxiolytic properties.The aim is to provide a theoretical foundation for further research and the application of koumine in clinical practice.展开更多
文摘Salvia triloba, traditionally known as Greek sage, has been used to enhance memory, as a sedative and to treat headaches. Pharmacological evaluation of purified extracts and isolated compounds of S. triloba were carried out on functional assays using two-electrode voltage clamp methods on recombinant GABA receptors expressed in Xenopus laevis oocytes. Bio-assay guided fractionation led to seven compounds being isolated from S. triloba: ursolic acid, carnosol, oleanolic acid, salvigenin, rosmanol, cirsimaritin and hispidulin. The purified extracts of S. triloba inhibited 54% of the current produced by 300 μM GABA at α1β2γ2L GABAA receptors. Ursolic acid, carnosol, oleanolic acid and rosmanol also acted as negative allosteric modulators. The flavonoids salvigenin, cirsimaritin and hispidulin acted as positive modulators when applied in the presence of low concentrations of GABA but in the presence of high concentrations of GABA acted as negative modulators, demonstrating a biphasic action. These results are consistent with the concept that Salvia triloba may have cognition enhancing properties. In most cases these activities are likely to be occurring via different modulatory sites on GABAA receptor complexes. It may be that the combination of these activities permits cognition enhancement whilst offering protection from convulsant activity.
文摘Natural regulatory peptides are biologically active compounds that are produced by various cells and provide a link among the main regulatory systems of the body. The field of research into the biologic activity of endogenous regulatory peptides is extremely vast. These peptides affect the cardiovascular, immune, reproductive, endocrine, digestive, and other systems, alter energy metabolism, and are especially effective in the regulation of the central nervous system. Despite of the wide range of preventive and therapeutic effects of natural regulatory peptides and proteins, their application in clinical practice is difficult. This is primarily because of their extreme instability, as they are rapidly degraded by proteases of the gastrointestinal tract, blood, cerebrospinal fluid, and other biologic media. Compounds with higher stability (i.e., a considerably longer half-life compared with that of natural molecules) and the ability to provide a directional effect on the various body systems were obtained from modifications of endogenous regulatory peptides. Synthetic analogs of regulatory peptides, as a rule, contain only natural amino acids in their composition, and their biodegradation does not lead to the formation of toxic products;thus, they have fewer side effects. This review focuses on the consideration of two synthetic regulatory peptides, Semax and Selank, which were the bases for the creation of new drugs that are used effectively in the treatment of various diseases of the nervous system. The synthetic analog of an adrenocorticotropic hormone 4-10 fragment (ACTH4-10) Semax is a powerful neuroprotective agent that is particularly effective as a therapy for stroke. Selank was synthesized on the basis of the natural immunomodulator tuftsin. Selank is a powerful anxiolytic that is used as a therapy for generalized anxiety disorder and neurasthenia without sedative and muscle-relaxant effects. This review presents the results of research aimed at studying the influence of these peptides on the transcriptome of brain cells. The problems of drugs developed based on the clinical activities of Semax and Selank are discussed separately.
文摘Anxiety is a significant mental health issue that substantially affects an individual’s quality of life. Feelings of uneasiness, irritability, and sleep disturbances characterize it. 4-Hydroxyphenyl acetic acid (4-HPAA) is identified in brain cells as a physiological byproduct of tyramine. This study hypothesizes that 4-HPAA may regulate anxiety due to its anxiolytic properties, acting as a modulator of the GABAergic system, which plays a crucial role in the pathophysiology of anxiety disorders. Our study aims to enhance the anxiolytic effects of 4-HPAA through chemical modification to improve its pharmacokinetic properties. Three derivatives, namely Isopropyl-4-hydroxy-[phenyl] acetate (IHPA), Isopropyl-4-hydroxy-[phenyl] acetate (MPAA), and 4-methoxyphenyl acetate (MPHA), have been synthesized from 4-HPAA. This assessment will use well-established animal models, specifically the Elevated Plus-Maze (EPM) and Zero Maze (EZM) tests, selected for their validity in replicating anxiety-like symptoms in animals. Chronic caffeine administration via drinking water (0.3 g/l for 14 days) was employed to induce an anxiety state for testing purposes. IHPA and MPAA demonstrated significant anxiolyticactivity when tested in the EPM and EZM experiments. Molecular docking simulations using AutoDock Vina indicated that 4-HPAA derivatives had docking scores ranging from −5.8 to −4.8 kcal/mol, compared to the standard anxiolytic medication Diazepam, which scored −7.1 kcal/mol. These scores suggest a potential for 4-HPAA derivatives to interact effectively with the Gamma-aminobutyric acid (GABA_A) receptor. In conclusion, our in vivo and in silico analyses indicate a promising anxiolytic potential for 4-HPAA derivatives.
文摘Objective:To investigate the anxiolytic activity of newly isolated compound by our lab called ursolic acid stearoyl glucoside(UASG) from the leaves of Lantana camam(L camam).Methods: Column chromatography was used to isolate UASG.Anxiolytic potential was experimentally proved and demonstrated through Elevated plus-maze,Open field and light and dark test. Results:The UASG showed marked increased in time spent(%) and number of frequent movements made by animals in open arm of elevated plus-maze apparatus.In light and dark model,UASG produced marked increase in time spent by animal,number of crossing and reduced duration of immobility in light box.Conclusions:UASG showed significant increase in number of rearing,assisted rearing and number of square crossed in open field established test model.UASG showed its anxiolytic effect in dose dependent manner.
基金supported by the National Key Research and Development Program of China (2021YFD2100402)the National Natural Science Foundation of China (81903275)the Fund of the Cultivation Project of Double First-Class Disciplines of Food Science and Engineering,Beijing Technology&Business University (BTBUYXTD202203)。
文摘Globally,the prevalence of anxiety and depression has reached epidemic proportions.Food-derived protein hydrolysates and peptides delivered through dietary supplementation can avoid the negative risks associated with traditional pharmaceuticals while delivering superior anxiolytic and antidepressant effects.This review summarizes current research on food-derived anxiolytic and antidepressant protein hydrolysates and peptides,and subsequently analyses their physicochemical characteristics and elaborates on their mechanisms.The aim of this work is to contribute to the in-depth study and provide a theoretical foundation for the development of related products to better serve patients with anxiety and depression.
基金This work was supported by the National Key Research and Development Program of China(2016YFA0501000 and 2016YFC1306700)the National Natural Science Foundation of China(31970939,81527901,81821091,31771167,31571090,and 31490592)+2 种基金the Science and Technology Planning Project of Guangdong Province of China(2018B030331001)the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences(2018PT31041)and Fundamental Research Funds for the Central Universities,China(2017FZA7003).
文摘Social defeat stress(SDS)plays a major role in the pathogenesis of psychiatric disorders like anxiety and depression.Sleep is generally considered to involve recovery of the brain from prior experience during wakefulness and is altered after acute SDS.However,the effect of acute SDS on sleep/wake behavior in mice varies between studies.In addition,whether sleep changes in response to stress contribute to anxiety is not well established.Here,we first investigated the effects of acute SDS on sleep/wake states in the active period in mice.Our results showed that total sleep time(time in rapid eyemovement[REM]and non-REM[NREM]sleep)increased in the active period after acute SDS.NREM sleep increased mainly during the first 3 h after SDS,while REM sleep increased at a later time.Then,we demonstrated that the increased NREM sleep had an anxiolytic benefit in acute SDS.Mice deprived of sleep for 1 h or 3 h after acute SDS remained in a highly anxious state,while in mice with ad libitum sleep the anxiety rapidly faded away.Altogether,our findings suggest an anxiolytic effect of NREM sleep,and indicate a potential therapeutic strategy for anxiety.
文摘Objective:To research the acute toxicity of Illicium verum(I.verum)fruit extracts and its action on central nervous system.Methods:The TLC and HPTLC techniques were used as fingerprints to determine the chemical components present in I.verum.Male albino rats and mice were utilized for study.The powdered material was successively extracted with n-hexane,ethyl acetate and methanol using a Soxhlet extractor.Acute toxicity studies were performed as per OECD guidelines.The CNS activity was evaluated on parameters of general behavior,sleeping pattern,locomotor activity,anxicty and myocoordination activity.The animals were trained for seven days prior to experiments and the divided into five groups with six animals in each.The drug was administered by intraperitoneal route according to body weight.The dosing was done as prescribed in each protocol.Results:Toxicity studies reported 2 000 mg/kg as toxicological dose and 1/10 of the same dose was taken as therapeutic dose Intraperitoneal injection of all extracts at dose of 200 mg prolonged phenobarbitone induced sleeping time,produced alteration in general behavior pattern,reduced locomotor activity and produced anxiolytic effects but the extracts do not significantly alter muscles coordination activity.The three extracts of I.verum at the dose of 200 mg,methanol extract was found to produce more prominent effects,then hexane and ethylacetate extracts.Conclusions:The observation suggested that the extracts of I. verum possess potent CNS depressant action and anxiolytic effect without interfering with motor coordination.
文摘Objective: To evaluate the neuropharmacological properties of Costus speciosus(C. speciosus) rhizome using different experimental mouse models. Methods: The anxiolytic effect was investigated by hole-board test, elevated plus maze and light/dark test, while central nervous system(CNS) depressant effect was evaluated by thiopental sodium-induced sleep test. Finally, antidepressant effect was evaluated by forced swimming test and tail suspension test. Results: In both elevated plus maze and hole board test, 400 mg/kg C. speciosus showed more significant CNS depressant effect than 1 mg/kg diazepam. Both 200 mg/kg and 400 mg/kg C. speciosus extract produced a significant dose-dependent decrease in onset of sleep. In forced swimming test, C. speciosus rhizome showed a decrease in duration of immobility in a dose-dependent manner. Imipramine(10 mg/kg) and C. speciosus extract at 400 mg/kg dose exhibited a significant reduction in duration of immobility in tail suspension test which provided additional evidence of antidepressant effect of C. speciosus rhizome. Conclusions: Our study indicates that C. speciosus rhizome possesses CNS depressant, anxiolytic and antidepressant-like activities. Further studies are warranted determine the exact phytoconstituents and mechanism of action responsible for the neuropharmacological effect.
基金Supported by grant from the General Project and Invention of Prince of Songkla University(SCI570371S)BRAND's Brain Research Centre,Bangkok,Thailand
文摘Objective: To elucidate the anxiolytic and free radical scavenging effect of methanolic extract of Apium graveolens(A. graveolens) in adult C57BL/6 mice.Methods: Sixty male mice were divided into 6 groups: control, vehicle, positive control and A. graveolens(125, 250 and 500 mg/kg). Different behavioral models of elevated plus maze, open field, light/dark, hole-board and pentobarbital-induced sleep were used to assess anxiety-like behavior. Biochemical parameters including monoamine oxidase-A(MAO-A) activity, lipid peroxidation, % inhibition of superoxide anion and glutathione peroxidase activity were measured. Histologic studies were also examined.Results: Mice receiving various doses of A. graveolens(125, 250 and 500 mg/kg)showed an alleviation of anxiety-like behavior as evidenced by the battery of behavioral tests. Likewise, A. graveolens treatment was found to significantly decrease MAO-A activity, lipid peroxidation as well as cause a significant increase of % inhibition of superoxide anion and glutathione peroxidase activity in both cortex and striatum. The total number of survival neurons found in the frontal cortex and striatum was significantly higher than that of the vehicle-treated group.Conclusions: Taken together, we showed that A. graveolens improve the behavioral changes which might be related to the inhibition of free radicals and modulation of MAOA activity resulting in an increased number of survival neurons. Our findings suggest the therapeutic potential of A. graveolens in the treatment of anxiety.
文摘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℃),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℃) 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.
基金support provided by Rajarambapu College of Pharmacy,Kasegaon,Sangli-415404Maharashtra,India and Krishna institute of medical sciences,Karad,Maharashtra,India for carrying out this research.
文摘Anxiety is an unpleasant state,which can critically decrease the quality of life is often accompanied by nervous behaviour and rumination.Niranthin is a lignan isolated from various Phyllanthus sources.The literature survey on niranthin highlights wide ranges of the therapeutic potentials.In a present study,based on our previous investigations,we evaluated pure,isolated and characterized niranthin as an anxiolytic agent.The niranthin[6-[(2R,3R)-3-[(3,4-dimethoxyphenyl)methyl]-4-methoxy-2-(methoxymethyl)butyl]-4-methoxy-1,3-benzodioxole]was purchased from commercial source and further subjected for assessment of its anxiolytic potentials using popular animal models including Elevated plus-maze model/test(EPM)and Light&Dark Exploration test(L&D).GABA-A receptor mediation was evaluated by pretreating the mice with the GABA-A receptor antagonist Flumazenil before the EPM task.Molecular docking simulation studies(pdb id:4COF)carried out by Vlife QSAR software showed that niranthin(docking score:−62.1714 kcal/mol)have shown comparatively best docking score compared to the standard drug Diazepam(docking score:−63.1568 kcal/mol).To conclude,Niranthin has probable potential in the management of anxiety disorder.Our in-silico and in-vivo analysis(indirectly)indicated the plausible role of GABA mediation for anxiolytic activity.Although,these studies are preliminary,future in depth experimental explorations will be required to use Niranthin as anti-anxiety drug in near future.
基金The project was funded by the Mongolian Foundation of Science and Technology of Mongolia(17AT05IN324,AJ).Parts of the work were supported by the National Science Foundation(IOS-0724962(JVM)and DBI-0421079(JVM)).
文摘Objective:To clarify the neuropharmacological profile of the Mongolian vetch,Astragalus mongholicus(Astragalus membranaceous var.mongholicus;synonym:A.mongholicus),extracts were evaluated for behavioral effects in rats and mice.Methods:An aqueous extract of A.mongholicus was made by boiling roots from freshlycollected plants in 2.5 volumes(w/v)of water for 60 minutes.An ethanol extract was made by incubating in 70%ethanol for 5 days at 25C.Effects of the aqueous extracts were evaluated in a forced swimming assessment of antidepressant effects,a hole-board test of exploratory behavior,an analysis of inhibition of aggression following electrical stimulation and influences on amnesia resulting from electroshock.Furthermore,effects of ethanol extracts of A.mongholicus were assessed on L-tryptophan induced twitches(indicating serotonin-mediated effects)and on hypothermia induced by apomorphine(indicating dopamine-mediated interactions)in mice.Results:Per os(PO)administration of the aqueous decoction of the vetch to rats increased the response in a forced swimming test as reflected in wheel rotations.However,the decoction had no significant effect on the exploratory behavior of rats in the hole-board test.Acute PO administration of the aqueous extract of A.mongholicus decreased the threshold for aggressive behavior and this effect persisted with subchronic administration.Chronic administration of the plant extract suppressed aggression of rats.An ethanol extract of A.mongholicus showed an antiserotoninergic action and had a significant influence on the hypothermia induced by apomorphine.Conclusion:A.mongholicus has a variety of potent psychotropic actions,suggesting influences on diverse neurotransmitter systems.
文摘In recent years,there has not been much progress in developing anxiolytic drugs.Amongst the barriers are the lack of clarity on the pathogenesis of anxiety disorders,low product conversion rates for developing drugs targeting the receptors,and species variability.Some scientists have focused on natural medicines,especially herbal medicines in traditional Chinese medicine.New drugs with excellent anxiolytic activity are hoped to be found in herbal medicines with anxiolytic effects.This mini-review summarised three Chinese herbal medicines with anxiolytic effects and anxiolytic herbal formulas used in the traditional Chinese medicine clinic.Several key issues that block the development of new anxiolytic drugs are also discussed.We hope to provide some ideas for researching and developing new anxiolytic drugs and studying anxiolytic components in traditional Chinese medicine.
基金Supported by Department of Genetie Engineering and Biotechnology.University of Chittagong.(Grant No.Ref No.CEB/AC-54/18-09-2010)
文摘Objective:To analyze in vivo neuro-pharmacological effects of Alpinia nigra as anxiety is a particular form of behavioral inhibition that occurs in response to novel environmental events.Methods:In present study,the extract of Alpinia nigra was evaluated for its central nervous system depressant effect using mice behavioral models,such as hole cross,open field and thiopental sodium induced sleeping time tests for its sedative properties and an elevated plusmaze test for its anxiolytic potential,respectively.Results:In anxiolytic study,the extract displayed increased percentage of entry into open arm ut the dose of 400 and 200 mg/kg.The extract produced a significant(P<0.01) increase in sleeping duration and reduction of onset of sleep compared to sodium thiopental at both doses(200 and400 mg/kg).The extract t.200 and 400 mg/kg) also showed a dose-dependent suppression of motor activity and exploratory activity of the mice in both open field and hole cross test.Conclusion:This study demonstrates that the treated extract has significant central nervous system depressant effect.Further studies on active constituent of the extract can provide approaches for therapeutic intervention.
文摘OBJECTIVE To investigate the relationship between the neurochemical and behavioral effects of inhibitors of cyclic nucleotide phosphodiesterases 2(PDE2) and PDE4 in the hope of identifying promising therapeutic targets and indications. METHODS Depression-and anxiety-like behaviors were evaluated by forced swimming,tail suspending and elevated plus maze tests. The memory enhancing effects were evaluated by Morris water maze test. RESULTS Inhibition of PDE4 results in antidepressant-like and memory-enhancing effects,in part due to increased cyclicAMP signaling.While targeting PDE4 subtypes(PDE4A-D) pharmacologically has proven challenging due to a highly conserved inhibitor-binding site in the catalytic region of the enzyme,some promise is offered by recently identified negative allosteric modulators of PDE4,which can act in a subtype-specific manner.While PDE2 has not been studied as extensively,it has been shown to be coded for by a single mammalian gene and to be highly expressed in the brain. Its inhibition results in anxiolytic-and antidepressant-like effects as wells as reducing oxidative stress and affording some degree of neuroprotection;these actions appear to be due to increased cyclicGMP signaling,even though PDE2 catalyzes the hydrolysis of both cyclicAMP and cyclicGMP. CONCLUSION Inhibitors targeting specific family of PDE may exhibit differential pharmacological effects and aid a more efficient pharmacotherapy towards neuropsychological conditions,while drug discovery efforts focusing on PDE2 are not as advanced as those for PDE4,some selective inhibitors are being developed and evaluated.
文摘We investigated the effects of a standardized extract of Caralluma fimbriata Wall (CFE) on learning and memory in mice using various behavioural models. Unusually, CFE exerts both nootropic and anxiolytic effects.
文摘In indigenous or folk medicine, Euphorbia hirta is a very popular herb and used as a palliative to treat various ailments including intestinal parasites, diarrhoea, vomiting, amoebic dysentery, asthma, bronchitis, emphysema, coughs, kidney stones, menstrual problems etc. The objective of this study is to evaluate the anxiolytic and sedative-like effects of the methanol extract from the leaves of Euphorbia hirta (Euphorbiaceae). Methanolic extract of Euphorbia hirta was evaluated for its CNS depression effect using mice behavioral models such as, elevated plus maze and hole board test for its anxiolytic potential where hole cross and pentobarbital-induced sleeping time tests were performed for its sedative properties, respectively. The test group received three different doses of the MEHL (100 mg/kg, 200 mg/kg and 300 mg/kg) orally. The positive control group received diazepam (1 mg/kg) orally where the negative control group received distilled water (10 ml/kg) orally. In elevated plus maze test, the extract exhibited significant (p d the number of open arm entry and time spent in open arm by mice compared to control group. In addition, the number of head dips and hole crosses significantly (p < 0.05) decreased by mice in hole board and hole cross tests respectively, compared to control group. Moreover, mice treated with MEHL significantly decrease the onset of sleep and increase the duration of sleep in pentobarbital-induced sleeping time test in mice compared to control group. The data obtained from the present study clearly demonstrate that the methanolic extract of Euphorbia hirta has potential anxiolytic and sedative-like activity in the animal behavioral models. And the findings represent a rational explanation for its use in traditional medicine for the management of neurological disorder.
基金Supported by Central Government Supports Local College Reform and Development Fund Talent Training Projects(2020GSP16)Undergraduate Innovation and Entrepreneurship Training Program of Heilongjiang Province(202310223122).
文摘Formononetin is an isoflavone phytoestrogen mainly existing in leguminous plants such as Trifolium pretense,Spatholobus suberectus,etc.Studies have proved that formononetin has good anti-inflammatory,antitumor,antioxidant,antidepressant,anxiolytic and other pharmacological effects.This paper summarizes the pharmacological action and molecular mechanism of formononetin,in order to provide a theoretical basis for the development and clinical application of formononetin.
文摘Bacopa monniera Linn. or Brahmi, a plant in the family Scrophulariaceae, is used as a traditional medicine for memory improvement, dementia like anxiety, depression, epilepsy etc. for a long time in Bangladesh. This study evaluated the anxiolytic effects of the methanolic extract of B. monniera (MEBM) in animal models of anxiety. For the further tests and phytochemical screening, the whole plant of B. monniera extracted following maceration method. The extract was evaluated for anxiolytic activity using light/dark box, elevated plus maze, marble burying and rota rod tests in mice at the doses of 50, 100, and 200 mg/kg body weight. Diazepam (1.0 mg/kg), an anxiolytic drug used as standard drug. MEBM showed a strong and dose-dependent anxiolytic effects in animal models of anxiety. MEBM significantly increased the time spent in the light compartment, the latency time, and the entries of open arms in light/dark and elevated plus maze tests. In addition, MEBM also significantly decreased the number of buried marbles in marble burying test and increased the time of performance in rota rod test (p < 0.05). These were the major findings of this study. Therefore, our results reported that MEBM possesses anxiolytic effects in animal models of anxiety that support the traditional use of this plant as a potent agent to combat anxiety.
基金Supported by Central Talent Training Project for the Reform and Development of Local Colleges and Universities(2020GSP16)Guidance Project of Key R&D Plan in Heilongjiang Province(GZ20220039).
文摘Koumine is an indole alkaloid monomer extracted from the Chinese herb Gelsemium elegans,which has a variety of pharmacological effects.This paper provides a comprehensive summary of the pharmacological effects and molecular mechanisms of koumine,with a particular emphasis on its mechanisms of action in the context of anticancer,anti-inflammatory,analgesic,and anxiolytic properties.The aim is to provide a theoretical foundation for further research and the application of koumine in clinical practice.
