Anti-anxiety Activity Research Articles

Anti-Anxiety Effect of Salvia hypoleuca

Background and objectives: Anxiety is a chronic and common disorder worldwide and impairs the quality of life of affected people. Herbal medicines have long been used to treat CNS related disorders. Salvia species are important medicinal plants that have shown various pharmacologic activities including CNS effects. Salvia hypoleuca is an annual and herbaceous plant which is endemic to Iran. The aim of this study was to evaluate the anxiolytic activity of the hydro-alcoholic, n-hexane, ethyl acetate and methanol extract of S. hypoleuca in mice. Methods: n-hexane, ethyl acetate, methanol and hydroalcholic extracts were prepared from aerial parts of Salvia hypoleuca. Anxiolytic activity of the extracts was evaluated using open field and hole-board tests. The mice were randomly divided into different groups and were treated with normal saline, diazepam, and the extracts of S. hypoleuca (500 mg/kg, ip). Results: The results of open field and hole-board tests showed that treatment of mice with the hydro-alcoholic and methanol extracts of S. hypoleuca(500 mg/kg, ip) produced a significant anxiolytic effect as compared to the normal control group. Conclusion: This study demonstrated that the hydro-alcoholic and methanol extracts of aerial parts of S. hypoleuca have anti-anxiety activity. The isolation and identification of the active compounds of the effective extracts are suggested.

COMBINED EFFECT OF SELECTIVE BIOACTIVE COMPOUNDS FROM PLANT ORIGIN IN AN ANIMAL MODEL OF ANXIETY

Objective: Evidence is emerging that specific combinations of bioactive compounds may be far more effective in protecting against several diseases as compared to the effect of a single compound. The present study was aimed to investigate the interactive effect of Diosgenin and Silymarin, the bioactive compounds from plant origin in an animal model of anxiety.
 Methods: Albino wistar rats of either sex were divided into five groups and treated for 5 d. Group I and II served as control and standard and test groups were treated with Diosgenin (100 mg/kg, p. o.), Silymarin (100 mg/kg, p. o.) and combination of Diosgenin (50 mg/kg, p. o.)+Silymarin (50 mg/kg, p. o.), respectively. Diazepam (1 mg/kg, i. p.) was used as a standard for the study. Anxiolytic effects were studied in the Elevated plus-maze, Hole-board test and Light/Dark model.
 Results: The results suggested that Diosgenin when given alone at a dose of 100 mg/kg, does not shown significant anxiolytic effect when as compared with control. Whereas, the compound Silymarin (100 mg/kg) shown significant anti-anxiety effect (P<0.01), independently. The same two bioactive compounds, given in combination at a dose of 50 mg/kg, (each), exhibited significant anxiolytic-like effect, potentially.
 Conclusion: It can be concluded that Diosgenin has got a synergistic effect on anti-anxiety action when given in combination with Silymarin.

Anti-anxiety effect of Aerva lanata (L.) using mice model

The present research aims to evaluate the anti-anxiety activity of ethanolic extract of Aerva lanata (L.) (Amaranthaceae). The study was performed using Albino mice of either sex. Ethanolic extract of Aerva lanata was administered at a doses of 100mg/kg and 400mg/kg body weight (p.o). The elevated plus maze (EPM) and Light dark transition (LDT) tests were used to determine the anti-anxiety activity. The results of the present study demonstrated that the mice treated with the Aerva lanata (L.) extract produced significant anxiolytic effect in both the animal models of anxiety, when compared to the control group.

Evaluation of anti-anxiety activity of Mucuna pruriens

Mucuna pruriens, also known as Velvet Bean, Mucuna pruriens has been used for centuries by Ayurvedic herbalists for overall wellness. Mucuna pruriens provides support for brain function, muscle health and libido. Mucuna pruriens has also been shown to have diuretic effects. It increases tissue resiliency and improves coordination. Mucuna can also increase testosterone levels, which in turn can lead to increased muscle mass and strength. It also supports the nervous and reproductive systems in the body. anti-oxidant activity of M. pruriens has been also demonstrated in vitro by its ability to scavenge DPPH radicals and reactive oxygen species. This is an excellent natural source of L-dopa and 5-hydroxy tryptophan (5-HT) Present study was designed to evaluate the anti-anxiety activity of Mucuna pruriens extract in Swiss albino mice. Three doses of Mucuna pruriens (100, 200,400 mg/kg, p.o.) and standard dose of Buspirone (5 mg/kg, i.p.) were used for evaluation of the anti-anxiety activity. The elevated plus maze (EPM) was used to take as a measure of antianxiety effect. Mucuna pruriens at the doses of 200 mg/kg and 400 mg/kg significantly reduced the time spent and no. of entries in closed arm, increased the time spent and entries into open arm in elevated plus maze (p<0.05) as compared to control group. These results indicate that MP may be possesses antianxiety property. Keywords: Anxiety, Elevated plus maze, Mucuna pruriens, Buspirone, Swiss Albino Mice.

Synthesis and Anxiolytic Activity of some novel benzotriazole derivatives

1,2,3-Benzotriazole (BTA) is a heterocyclic compound with three nitrogen atoms. It is a polar and colourless compound which can be used for its great versatility. The enormous investigations on derivatives of benzotriazole reveal wide applicability for tagging and delivering a number of heterocyclic nuclei with this molecule. In the present work synthesis of several derivatives of 2-(substituted)-5-[(N-benzotriazolomethyl)-1,3, 4-thiadiazolyl]- imidazole-2-thione has been synthesized and are evaluated for their anxiolytic activity. The antianxiety activities of the synthesized derivatives were evaluated using EPM test and Bright and dark box test experimental models of anxiety. All results were expressed as mean± standard error mean (SEM) and analysed by one-way ANOVA. Post-hoc comparisons were performed by applying Dunnet’s test. P <0.05 was considered statistically significant. Keywords: Benzotriazole; Thiadiazole; Thiazolidinone; Anxiolytic Activity; Anxiety; Elevated Plus Maize; Bright and Dark Arena.

Anxiolytic and anticonvulsant activity followed by molecular docking study of ceramides from the Red Sea sponge Negombata sp

The chemical investigation of the Red Sea sponge Negombata sp. led to isolation and structure elucidation of five new ceramides N ((2S,3R,4E,8E)-1,3-dihydroxyhexacosa-4,8-dien-2-yl)pentadecanamide (1), N-((2S,3R,E)-1,3-dihydroxynonadec-4-en-2-yl)stearamide (2), N-[(2S,3R,E)-1,3 dihydroxyhexacos-4-en-2-yl]palmitamide (3), N-((2S,3R)-1,3-dihydroxydodecan-2-yl)tetradecanamide (4), N-[(2S,3S,4R)-1,3,4- trihydroxypentadecan-2-yl] palmitamide (5). Structure elucidation was achieved using spectroscopic techniques, including 1D and 2D NMR and HRMS. The isolated ceramides were tested for anti-anxiety action in the elevated plus maze and the light-dark transition box. Mice given diazepam or compounds number 1, 2, 3, and 5 spent longer time in the light area of the light-dark box. However, compound 4 did not produce a similar effect. Similarly, testing anti-anxiety action in the elevated plus maze test showed that the compounds number 2, 3, and 5 or diazepam were able to prolong the open arm time %. Meanwhile, compounds 1 and 4 failed to produce a similar response. In addition, the anticonvulsant action of the ceramides was assessed employing pentylenetetrazole-induced seizures, where some ceramides prolonged the time to death due to pentylenetetrazole in vivo. In silico testing of the isolated ceramides displayed reasonable GABA receptor modulator binding at the benzodiazepines site. Ceramide 1 showed slightly stronger interaction with the GABA receptor over other ceramides which is compatible with the results of their anxiolytic activity.

Glacial Acetic Acid Catalyzed Synthesis, Physicochemical and Biological Evaluation of Benzodiazepines as Potent CNS Agents.

Approach for green chemistry for chemical synthesis is found to be very efficient as it makes the reaction more easily, less tedious, maximize desired products and minimize by-products. Utilizing this approach 1, 5-benzodiazepines and its derivatives have been synthesized and evaluated for skeletal muscle and antianxiety activity. 1, 5-benzodiazepine derivatives have attracted great attention due to its diversity of pharmacological activities and its application in heterocyclic synthesis and medicines. The target compounds were synthesized by first reacting o-phenylenediamine with acetophenone to yield 1, 5-benzodiazepines. In the next step the NH of 1, 5-benzodiazepines were chloroacetylated and then the chloro group was substituted with different anilines. The structures were confirmed on the basis of their TLC, IR, 1H NMR and CHN elemental studies. The physicochemical parameters were determined for BBB penetration through online software. The Log P values of the compounds tested showed that compounds have the potential to be CNS active. The compounds were evaluated for the skeletal muscle relaxant activity and antianxiety activity. It was investigated that 1, 5-benzodiazepines derivatives possess significant differences between control group and treated group. Among these derivatives, the compound bearing chloro group possesses the highest skeletal muscle relaxant and antianxiety activity.

Screening of aerial parts of the plant Clerodendrum paniculatum Linn for anti-anxiety activity

The present study was undertaken to investigate and validate the traditional claims of Clerodendrum paniculatum Linn for its anti-anxiety activity. C. paniculatum linn belongs to Verbenacae family. Ethnomedical importance of various species of Clerodendrum genus has been reported in various indigenous systems of medicines and folk medicines. It is used as a medicine for the treatment of sore eyes, gonorrhoea, urinary tract infection and kidney problems. Till date there are no reports available regarding its pharmacological properties of hence, it is therefore worthwhile to study the unrevealed properties of this plant. The shade dried aerial parts of plant were extracted by extracted using ethyl acetate, petroleum ether and aqueous as a solvent. Obtained extracts were subjected for phytochemical screening and antianxiety activity was studied using elevated plus maze and light and dark models. Results of the phytochemical screening revealed the presence of flavonoids, tannins, glycosides, saponins, and terpenoid like compounds. In addition, among the extracts studied for anti-anxiety activity of ethyl acetate extract shown significant activity comparable with standard drug, diazepam. Petroleum ether and aqueous extracts shown least anti-anxiety activity in comparison with the standard.

Screening of aerial parts of the plant Clerodendrum paniculatum Linn for anti-anxiety activity

Screening of aerial parts of the plant Clerodendrum paniculatum Linn for anti-anxiety activity

Evaluation of anti-anxiety activity of Cocos nucifera endocarp on anxiety models

Evaluation of anti-anxiety activity of Cocos nucifera endocarp on anxiety models

Antianxiety and Antidepressant Activity Guided Isolation and Characterization of Gossypetin from Hibiscus sabdariffa Linn. Calyces

The present study was designed to evaluate the antianxiety and antidepressant potential of Hibiscus sabdariffa Linn. (Malvaceae) calyces, which have been used traditionally as a sedative and for treating other nervous disorders. The study focussed on isolating active principle(s) using bioactivity guided approach. The bioactive ethanol extract of H. sabdariffa calyces was partitioned with ethyl acetate to obtain ethyl acetate soluble and insoluble fractions. The two fractions were evaluated for antianxiety and antidepressant activity. The bioactive ethyl acetate soluble fraction was subjected to successive column chromatography to obtain six fractions (F1-F6). Among the six fractions, only F4 exhibited significant antianxiety and antidepressant activity on Elevated Plus Maze Model and Forced Swim test, respectively. Column chromatography of F4 yielded three sub-fractions (F4.1-F4.3). Bioactive F4.3 was further subjected to column chromatography which yielded three subfractions – F4.3.1-F4.3.3, and a yellow crystalline compound (HS-1) was isolated from F4.3.2. Based on UV, IR, NMR and MS studies the isolated compound was characterized as gossypetin. Antianxiety and antidepressant activity of HS-1 was evaluated on EPM and FST, respectively. The study showed that gosypetin exhibits significant antianxiety and antidepressant activity at the dose of 5 and 20 mg/kg po, respectively. Present study validates the traditional use of H. sabdariffa calyces in nervous disorders. Gossypetin is the anxiolytic and antidepressant constituents of H. sabdariffa calyces.

Novel Pyrazolo[4, 3-c]Quinolin-3-One Derivatives as PDE5A Inhibitors.

PDE5A is a phosphodiesterase which specifically hydrolyzes the cGMP to GMP. It takes part in several physiological and pathological pathways and is considered an important drug target. Currently, PDE5 inhibitors (ex; Sildenafil, Tadalafil) available in the market are not only being used for the treatment of erectile dysfunction but at the same time, they are also in clinical trials being investigated as anticancer agents. In this work, we have examined pyrazolo [4,3-c]quinolin-3-ones as PDE5A inhibitors. Pyrazolo [4,3-c]quinolin-3-ones are the class of tricyclic heterocyclic derivatives having a variety of therapeutically interesting drug candidates known for their anti-inflammatory, anti-viral, anti-anxiety and anti-cancer activity. Therefore, synthetic methods providing access to pyrazolo [4, 3-c] quinolin-3-ones are immensely valuable. Here, we are reporting a simple but efficient route for the synthesis of novel 8-morpholino-2-aryl - 2, 5-dihydro-3H-pyrazolo [4, 3-c] quinolin-3-one derivatives. Further, molecular docking studies of synthesized compounds with human PDE5A protein showed that all the compounds exhibited good docking score in comparison with known inhibitors. In addition, all the synthesized molecules were evaluated against HCT116 cell lines for their antitumor activity. Among all the synthesized compounds, compound 5a, 5d, and 6e showed better cytotoxicity. Thus, these derivatives can be studied as potential inhibitors of PDE5A.

Anxiolytic Action of Taurine via Intranasal Administration in Mice.

Taurine has a number of beneficial pharmacological actions in the brain such as anxiolytic and neuroprotective actions. We explored to test whether taurine could be transported to the central nervous system through the intranasal route. Following intranasal administration of taurine in mice, elevated plus maze test, activity cage test and rota rod test were carried out to verify taurine’s effect on anxiety. For the characterization of potential mechanism of taurine’s anti-anxiety action, mouse convulsion tests with strychnine, picrotoxin, yohimbine, and isoniazid were employed. A significant increase in the time spent in the open arms was observed when taurine was administered through the nasal route in the elevated plus maze test. In addition, vertical and horizontal activities of mice treated with taurine via intranasal route were considerably diminished. These results support the hypothesis that taurine can be transported to the brain through intranasal route, thereby inducing anti-anxiety activity. Taurine’s anti-anxiety action may be mediated by the strychnine-sensitive glycine receptor as evidenced by the inhibition of strychnine-induced convulsion.

A Comparative Pharmacological Evaluation of Antianxiety Activity of Raw and Traditionally Shodhita (Processed) Rhizome of Vacha (Acorus calamus L.)

Background: Vacha (Acorus calamus L.; Acoraceae), one of the well-known drug of Ayurvedic pharmacopeia, is highlighted for its Medhya (brain tonic), Sanjnasthapana (restores lost consciousness), Deepana (appetizer), Pachana (digestive), etc., properties and hence used extensively in therapeutics. Ayurvedic pharmacopeias like Chakradatta, Bhaishajya Ratnavali, and Ayurvedic Pharmacopoeia of India (API) have recommended Shodana (processing) of Vacha using certain media like Gomutra, Mundi Kwatha, Gandhodaka, etc. It has been reported by us that subjecting to Shodhana is not only safe to use but also enhances the therapeutic activity of Vacha. Aim: To assess the antianxiety activity of raw and shodhita (processed) Vacha rhizomes in different experimental animal models. Materials and methods: Swiss albino mice of either sex weighing 24 ± 4 g, of either sex, were administered with raw and shodhita Vacha (16 mg/kg body weight) along with distilled water. Diazepam (2 mg/kg body weight) was used as a standard drug. Results and conclusion: Pretreatment with both raw and classically processed Vacha samples exhibited significant antianxiety activity; among them, the observed activity in shodhita Vacha was found to be better. The present study confirms the antianxiety activity of raw and shodhita Vacha. But when subjected to the traditional Shodhana procedure, the efficacy of Vacha rhizomes get enhanced.

Synthesis and Evaluation of Antianxiety Activity of Novel Coumarin Derivatives on Swiss Albino Mice

Synthesis and Evaluation of Antianxiety Activity of Novel Coumarin Derivatives on Swiss Albino Mice

Pharmacological models to appraisement of antianxiety activity in experimental animals

The disease related to brain is very challenging task in the area of neuroscience research. Anxiety is one of the central nervous system disorders in which human feel excessive and unusual fear. Several antianxiety medicines available in market to treat and suppress this problem, but there is lack of evaluation methods available for them. The present review contains all the models such as plus maze apparatus, zero maze apparatus, forced swim apparatus, and open field methods, which are available for pharmacological evaluation of antianxiety. Accuracy can be achieved using these models in a comparative way and one has not to depend on any one model. Several modifications are also possible with these models to achieve accurate and precise result. Working principle of models is enlisted in this review to make them better understandable.

Neuropharmacological Profile and Chemical Analysis of Moroccan Ormenis mixta L.

Ormenis mixta L. is traditionally used for central nervous system (CNS)-related diseases. Its anti-stress properties have received attention in Moroccan traditional medicine and aromatherapy. However, no pharmacological studies have yet been undertaken on this plant in Morocco. The present study provides a preliminary phytochemical screening and psychopharmacological profile of the essential oil and aqueous extract from Ormenis mixta L. by using behavioral tests in vivo, at graded doses. The result of this research shows that Ormenis mixta L. was safe up to 2 g/kg b.w. (body weight) in the acute toxicity study, possesses potential psychostimulant effect, and has antianxiety and antidepressant-like activity. This activity profile of Ormenis mixta L. was similar to the typical psychostimulant, caffeine. The exact mechanism of action underlying this stimulant-like effect should be clarified with further detailed studies. These results explained the extensive use of Ormenis mixta L. as a traditional medicine in Morocco.

Cocrystal of nutraceutical sinapic acid with Active Pharmaceutical Ingredients ethenzamide and 2-chloro-4-Nitrobenzoic acid: Equilibrium solubility and stability study

Sinapic acid (SNP) is a nutraceutical compound of hydroxybenzoic acid derivative which possesses anti-oxidant, anti-microbial, anti-inflammatory, anti-cancer, and anti-anxiety activity properties. In the present work, two cocrystals of SNP with two active drug ingredients such as Ethenzamide (ETZ) and 2-chloro-4-nitrobenzoic acid (CNB) are reported. Both the cocrystals were synthesized via simple solvent evaporation method and the crystal structures were characterized by Single Crystal X-ray Diffraction (SC-XRD) techniques. The cocrystals were formed via robust acid-amide heterosynthon and acid-acid homosynthon between SNP and drug molecules. Both the cocrystals were crystallized in monoclinic crystal system with P 21/c space group. The synthesized cocrystals were further characterized by DSC, PXRD, FT-IR, and 1H NMR techniques. The solubility study in purified distilled water and in 0.1 N HCl solution demonstrate that there was no increment in the solubility of drug molecules in the cocrystals in both purified water and in 0.1 N HCl solution. The synthesized cocrystal exhibited six months stability at ambient conditions (∼25 °C, 60–65% RH).

Isolation, Characterization and Antianxiety Activity of Pentacosan-13-ol from Ferula sumbul Hook. Roots

Ferula sumbul Hook. (Apiaceae) has been traditionally used as a sedative in hysteria and other nervous disorders. Present study aims to isolate the antianxiety constituent(s) from F. sumbul roots using bioactivity guided fractionation approach. Dried coarsely powdered of F. sumbul roots were subjected to successive exhaustive Soxhlet extraction using petroleum ether, chloroform and ethanol. Finally, decoction of the marc was prepared using distilled water. The extracts were screened for antianxiety activity in mice using elevated plus maze model at three different dose levels. Chloroform extract, exhibiting significant antianxiety activity, was subjected to column chromatography to obtain 4 fractions (F1-F4) which were further evaluated for antianxiety activity. Column chromatography of F4 yielded 5 sub-fractions (F4.1-F4.5) and a white amorphous compound. All these were evaluated for antianxiety activity. Characterization studies elucidated the structure to be pentacosan-13-ol. The compound exhibited significant antianxiety activity at the dose of 20 mg/kg, po. Present study validates the traditional use of F. sumbul roots in nervous disorders. Pentacosan-13-ol is the antianxiety constituent of F. sumbul roots. This is the first report on antianxiety activity of F. sumbul roots.

N1-benzenesulfonyl-2-pyrazoline hybrids in neurological disorders: Syntheses, biological screening and computational studies.

A novel series of 1,3,5-trisubstituted-2-pyrazolines (5a-5t) was prepared via Claisen Schmidt condensation, followed by heterocyclization with hydrazine hydrate, substitution of N1 hydrogen of 2-pyrazoline nucleus with 4-chlorobenzenesulfonylchloride, applying conventional and green chemistry approaches. Among the two, microwave assisted organic synthesis (MAOS) emerged as a better synthetic tool in terms of faster reaction rate and high yield. Various physicochemical and spectral studies were conducted to characterize the synthesized derivatives including- IR, Mass, 1H-NMR, 13C-NMR and elemental analysis. During pharmacological evaluation, compound 5b showed excellent anti-anxiety activity and compound 5k exhibited the best antidepressant effect at the tested doses, 50 and 100 mg/kg b.w., being comparable to diazepam and imipramine, respectively. The docking experiments confirmed the probable mechanism of neuropharmacological action, showing excellent affinity towards MAO-A target protein, which was also evidenced from some of the key interactions with binding site residues Ala68, Tyr69 and Phe352. Furthermore, complimentary in silico pharmacokinetic recital without any potential risk of neurotoxicity (as evaluated by rotarod and actophotometer tests), or carcinogenicity, mutagenicity, reproductive toxicity, acute toxicity and irritancy (as predicted by LAZAR and OSIRIS programs) signified their probable use in depression and anxiety disorders.