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Six compounds were isolated from the roots of Ephedra sinica Stapf using various chromatographic techniques such as silica gel column chromatography, thin layer chromatography and semi-preparative HPLC. Their chemical structures were identified by analysis of physicochemical properties and spectral data, and determined as (Z)-docosanylferulate (1), (E)-docosanylferulate (2), bis (2-ethylheptyl) phythalate (3), 2,2′-oxybis (1,4-di-tert-butylbenzene) (4), diisobutyl phthalate (5), bis (2-ethylhexyl) phthalate (6). Among them, compound 1 is a new compound, compounds 2-4 were first isolated from Ephedra. A corticosterone-induced PC-12 cell injury model was used for compound activity screening. The results showed that compounds 1 and 5 significantly improved corticosterone-induced PC-12 cell injury and significantly increased 5-HT7 receptor protein expression in the cells, indicating potential antidepressant activity.
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The present study was undertaken to evaluate the anticonvulsant and antidepressant effects of Ascotheca paucinervia leaves on mice by using strychnine at 2.5mg/kg to induce convulsions and the forced swimming test to create a stressful situation, respectively. Concerning convulsions, only the 500mg/kg extract significantly increases (p<0.001) the time to onset of convulsions and it non-significantly reduces the duration of convulsions induced by strychnine. In addition, the extract reduces very significantly in a dose-dependent manner the time of immobility and it significantly increases the swimming time as well as the climbing time at both doses. At the same time, the estimation of the acute toxicity of the extract from the leaves of Ascotheca paucinervia according to guideline No. 425 of the OECD (2022) shows that the latter is weakly toxic and its LD50 is greater than 5000mg/kg. In addition, the evaluation of the sedative effect of this extract shows that it produces a dose-dependent sedative effects and at doses of 250m/kg and 500mg/kg, the extract significantly potentiates the sleep induced by phenobarbital. In summary, the results obtained suggest that Ascotheca paucineervia leaves extract possesses anticonvulsant and antidepressant effects.
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Background: Prunus dulcis (almond) contains high amounts of Inositol hexakisphosphate (IP6) which has proven antidepressant effects. Hence this study was done to evaluate the effects of Prunus dulcis on mice models of depression.Methods: Tails suspension test (TST) and forced swim test (FST) are usually used to assess the antidepressant activity in animal models. They were employed to analyse the effectiveness of Prunus dulcis before and after two weeks of the study period and the results were compared. The animals were divided into 4 groups of 6 mice each.group-1 (Normal control); group-2 was given fluoxetine 10 mg/kg; group- 3 and group- 4 were given 600 mg/kg and 1200 mg/kg of Prunus dulcis extract respectively. All the animals were on standard chow diet the entire duration of the study.Results: Prunus dulcis (almond) is found to be effective in treating depression, by significantly reducing the immobility period on test group 1 in forced swim test (p<0.05) and test group 2 in tail suspension test (p<0.05).Conclusions: The results clearly indicate the beneficial effects Prunus dulcis (almond) on mice models of depression. Further studies are required to prove its effectiveness in humans.
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Background: The objective of this study was to evaluate efficacy of 5HT3 receptor antagonist ondansetron antidepressant activity in physical induced swiss albino mice.Methods: Study was placebo controlled, randomized laboratory based comparative study with prior permission of Institutional animal ethical committee. Experimental animals were divided in to seven groups as control (distilled water 10ml/kg), standard Fluoxetine two doses (10mg/kg and 20mg/kg) , test drug ondansetron three doses (0.5mg/kg, 1mg/kg and 2mg/kg) and combinations of test and standard (0.5mg/kg + 10mg/kg).The drugs were administered intraperitonium and antidepressant activity was recorded using physically induced depression models tail suspension test and despair swim test.Results: Ondansetron treated albino mice groups with dose dependent increase of 0.5mg/kg, 1.0mg/kg and 2.0mg/kg showed significant decrease in antidepressant activity and increase in catalepsy score when compared with fluoxetine 10mg/kg and 20mg/kg. Combination doses showed stastically significant antidepressant activity.Conclusions: The present study indicates ondansetron showed promising antidepressant activity due to its ability to modulate serotonergic system and has proved to be safe in the dose range of 0.5mg/kg, 1mg/kg and 2mg/kg in mice.
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Background: In recent years, the search for novel pharmacotherapy from medicinal plants for psychiatric illness was significantly progressed. The present study was performed to evaluate the antidepressant activity of ethanolic extract of Lagenaria siceraria in animal models.Methods: The antidepressant activity of ethanolic extract of the fruit of L. siceraria in rats was assessed using forced swim test and tail suspension test. Imipramine at 15 mg/kg was used as standard antidepressant drug.Results: The ethanolic extract of L. siceraria fruit (EELS) was significantly and dose-dependently reduced the duration of immobility after repeated treatment for 7 days in Forced swim test and Tail suspension Test. But combination of L. siceraria (200mg/kg) with Imipramine gave a highly significant result (p<0.001) in reduction of immobility duration and the effect of high dose (400mg/kg) with imipramine (15mg/kg) did not decrease the duration of immobility period in both animal models at end of the study. In this work the dose of 400mg/kg afforded more protection than the imipramine.Conclusions: The results obtained from this study was indicate that the antidepressant activity of L. siseraria.
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OBJECTIVE: The aims of the present study were to explore the behavioural effects and to understand the possible mode of action of Bacopa monnieri extract (BME) on chronic unpredictable stress (CUS) induced depressive model and the biochemical alterations such as brain derived neurotrophic factor (BDNF), Akt, cyclic-AMP response element binding (CREB) protein level in the hippocampus of rats. METHODS: We examined the effects of chronic administration of BME on CUS exposed rats for 28 days. Behavioural changes were assessed by sucrose consumption and open field test to assess the effect of BME on CUS-induced depression. The mechanisms underlying antidepressant like action of BME was further evaluated by measuring levels of BDNF, Akt, and CREB in the hippocampus of rat brain and compared with the standard tricyclic antidepressant drug imipramine (20 mg/kg body weight). RESULTS: Exposure to CUS for 28 days produced depression-like behavior in rats, as indicated by significant decreases in sucrose consumption, locomotor activity including decreased BDNF, Akt and CREB levels in the hippocampus. Daily administration of BME at a dose of (80 mg/kg body weight) significantly reverses the behavioral alteration and restored the normal level of BDNF, total and phospho-Akt, total and phospho CREB in the hippocampus of CUS induced rats as compared to vehicle treated control rats. CONCLUSION: These findings suggest that BME ameliorates CUS induced behavioural depression in rats and that can be used as a potent therapeutic agent in treating depressive like behavior.
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Animals , Rats , Bacopa , Brain , Brain-Derived Neurotrophic Factor , Depression , Hippocampus , Imipramine , Motor Activity , Response Elements , SucroseABSTRACT
Abelmoschus manihot (L.) Medic., a folk herbal medicine in China, is a flowering plant belonging to Abelmoschus L. genus and Malvaceae family, which has been reported with an antidepressant activity. The study was designed to isolate flavonoids from Abelmoschus manihot corolla and explore the action mechanism of antidepressant activities. The flavonoids were isolated and purified by D101 macroporous resin column, polyamide column and Sephadex LH-20 sequentially and identified as myricetin-3-O-β-D-glucoside (1), gossypetin-8-O-β-D-glucuronide (2, G-8-G), gossypetin-3'-O-β-D-glucoside (3), quercetin-3'-glucoside (4, Q-3-G), isoquercitrin (5, IQT), hyperoside (6, HY), myricetin (7), quercetin (8, QT). Compounds 2, 4, 5, 6 and 8 (15, 30 and 60 mg·kg-1) were orally administered to mice and the reaction was observed in tail suspension test (TST) and forced swimming test (FST). Western blot analysis was used in determination of the protein expressions of brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB) and phosphorylation eukaryotic elongation factor 2 (p-eEF2). The results revealed that only Q-3-G and G-8-G (15, 30, 60 mg·kg-1) significantly reduced the immobility time in FST and TST. Furthermore, Q-3-G and G-8-G remarkably increased the expression of BDNF and TrkB, and decreased the expression of p-eEF2. These results suggest that Q-3-G and G-8-G had an obvious antidepressant activity via up-regulation of BDNF expression. The new observation will provide a new direction in the development of antidepressant in the treatment of major depressive disorder (MDD).
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As major active components of the plant of Guttiferae family, polycyclic polyprenylated acylphoroglucinols (PPAPs) have become a hot topic in natural product studies for their novel structures and varied bioactivities such as antibacterial, antiviral, antitumor, and antidepressant activities. In this paper, the chemical structures and bioactivities of 226 natural PPAPs have been summarized. It may provide the reference for the further studies of PPAPs.
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Zingiber officinale Roscoe, commonly known as ginger, is a traditional herb used to treat various disorders. In this study, we evaluated potential pharmacological effects of ethanolic extracts of Z.Officinale with respect to central nervous system (CNS) activity in mice. Role of ethanolic extract of ginger on CNS activity in mice was studied using models of elevated plus maze test, barbiturate-induced sleeping time, tail suspension test, hot-plate and tail-flick test. Ginger extract was administered to mice at single doses of 50 and 200 mg/kg, perorally while diazepam (1 mg/kg), morphine (5 mg/kg) and imipramine (30 mg/kg) intraperitoneally were used as standard drugs. The results showed that the ginger extract at all dose levels significantly exhibited anxiolytic activity increased the sleeping latency but reduced the sleeping time. Tail suspension test showed that the extract at both the doses was able to induce a significant decrease in the immobility time, similar to imipramine, a recognized antidepressant drug. Tail-flick and hot-plate tests demonstrated antinociceptive property of ginger extract, similar to morphine, a recognized antinociceptive agent. Higher dose level (200 mg/kg) showed better protective effects. Phytochemical screening of ethanolic extract revealed the presence of various phytoconstituents such as phenolic compounds, flavonoids, tannins, anthocyanins, carbohydrates, glycosides, proteins, resins and volatile oils. The possible mechanism by which ginger exhibited the significant beneficial effects on various CNS models in mice could be attributed to its antioxidant potential.
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Introduction: Depression belongs to the heterogeneous group of mental disorders characterized by extreme exaggerations and disturbance of mood, which adversely affect cognition and psychomotor functions. It results from abnormal brain mechanisms functionally deficient monoaminergic (noradrenaline and/or 5-hydroxytryptamine) transmission in the central nervous system. Aims and Objectives: To evaluate comparatively the Anti- depressant activity of Berberis aristata (Daru haridra) in albino rats after inducing experimental depression using different methods. Materials and methods: The antidepressant activity of aqueous extract of berberis aristata was screened by tail suspension method and the forced swimming test and compared with the control and standard drug (fluoxetine) for two weeks. Group1- were kept as control. Group 2- were treated with fluoxetine in a dose of 14mg/kg/day as standard drug for one week. Group 3, 4 and 5- were given aqueous extract of berberis aristata intraperitoneally in three graded doses 400,800 and 1600mg/kg/day respectively for two weeks. Results: berberis aristata exhibits antidepressant activity depicted by reduction in the immobility time when compared to the control group. The onset of action was after few days according to the dose of the test drugs following their administration. The effect is comparable with that of standard drug fluoxetine which may be attributed to the phytoconstituents like berberine, berbamine and palmitine, among them most probably with berberine alkaloid. The berberine alkaloid is known to inhibit the monoamine oxidase enzyme particularly monoamine oxidase- A isoform. berberine influenced either dopaminergic system by monoamine oxidase-B inhibiting property or by blocking the reuptake of dopamine by inhibiting its transporter. Conclusion: Berberis aristata has significant antidepressant activity demonstrated by tail suspension and forced swimming test compared to the test drug.
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Helianthus annuus seeds contain various chemical components and evaluate different biological activities. The present study was carried out to investigate the central nervous system (CNS) activity of methanolic extract of Helianthus annuus seeds in mice model. General behaviour, antidepressant activity and anxiolytic activity was observed. The results revealed that the methanol extract of Helianthus annuus seeds at 100 and 200 mg/kg caused a significant increase in the spontaneous activity (general behavioural profile), moderate increase in anxiolytic activity (light-dark box and elevated plus maze test) and remarkable increase in antidepressant activity (tail suspension test). The results suggest that methanol extract of Helianthus annuus exhibit significant antidepressant and moderate anxiolytic activity in tested animal models.
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The objective of this work was to evaluate the effects of standardized hydroalcholic extract of Commiphora mukul (HECM) in animal model of chronic stress medicated depression, namely olfactory bulbectomy (OBX) model in rats. Effects of 14-day (subacute) oral pretreatment of HECM (50, 100 and 200 mg/kg) were evaluated on depression and stress related parameters on OBX rats. Separate groups for sham control, OBX control and positive controls namely imipramine (20 mg/kg), fluoxetine (30 mg/kg) and desipramine (15 mg/kg) were also maintained. Behavioral and physiological parameters in open field and elevated plus maze were recorded. HECM showed dose-dependent reversal of OBX-induced physiological effects such as reduction of body weight, body temperature, heart rate and serum sodium concentration. HECM also showed reversal effects on OBX induced food intake increase and hyperactivity in open field and elevated plus maze paradigm. In conclusion, HECM demonstrated restorative effects in OBX induced depression model in rats probably due to stress reliving mechanisms.
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Helianthus annuus seeds contain various chemical components and evaluate different biological activities. The present study was carried out to investigate the central nervous system (CNS) activity of methanolic extract of Helianthus annuus seeds in mice model. General behaviour, antidepressant activity and anxiolytic activity was observed. The results revealed that the methanol extract of Helianthus annuus seeds at 100 and 200 mg/kg caused a significant increase in the spontaneous activity (general behavioural profile), moderate increase in anxiolytic activity (light-dark box and elevated plus maze test) and remarkable increase in antidepressant activity (tail suspension test). The results suggest that methanol extract of Helianthus annuus exhibit significant antidepressant and moderate anxiolytic activity in tested animal models.
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A new series of 2-(5-methyl-2,3-dioxoindolin-1-yl)acetamide derivatives were synthesized and evaluated for their anticonvulsive activity in a pentylenetetrazole (PTZ)-evoked convulsion model and antidepressant activity in the forced swimming test (FST) model. Eleven synthesized compounds were found to be protective against PTZ-induced seizure and showed the anticonvulsant activity. In addition, four of the synthesized compounds (4l, 4m, 4p and 4q) showed potent antidepressant-like activity. Among these compounds, compound 4l was found to have the most potent antidepressant-like activity, and significantly reduced the duration of immobility time at 100 mg/kg dose level when compared to the vehicle control, which is similar to the reference drug fluoxetine.
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<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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 plus-maze test for its anxiolytic potential, respectively.</p><p><b>RESULTS</b>In anxiolytic study, the extract displayed increased percentage of entry into open arm at 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 and 400 mg/kg). The extract (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.</p><p><b>CONCLUSION</b>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.</p>
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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 plus-maze test for its anxiolytic potential, respectively.Results:In anxiolytic study, the extract displayed increased percentage of entry into open arm at 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 and 400 mg/kg). The extract (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.
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Present anti-PD and -AD drugs have limited symptomatic activity and devoid of neuroprotective and neurorestorative property that is needed for disease modifying action. The complex pathology of PD and AD led us to develop several multi-target neuroprotective and neurorestorative drugs with several CNS targets with the ability for possible disease modifying activity. Employing the pharmacophore of our anti-parkinson drug rasagiline (Azilect, N-propagrgyl-1-R-aminoindan), we have developed a series of novel multi-functional neuroprotective drugs (A) [TV-3326 (N-propargyl-3R-aminoindan-5yl)-ethyl methylcarbamate)], with both cholinesterase-butyrylesterase and brain selective monoamine-oxidase (MAO) A/B inhibitory activities and (B) the iron chelator-radical scavenging-brain selective monoamine oxidase (MAO) A/B inhibitor and M30 possessing the neuroprotective and neurorescuing propargyl moiety of rasagiline, as potential treatment of AD, DLB and PD with dementia. Another series of multi-target drugs (M30, HLA-20 series) which are brain permeable iron chelators and potent selective brain MAO inhibitors were also developed. These series of drugs have the ability of regulating and processing amyloid precursor protein (APP) since APP and alpha-synuclein are metaloproteins (iron-regulated proteins), with an iron responsive element 5"UTR mRNA similar to transferring and ferritin. Ladostigil inhibits brain acetyl and butyrylcholinesterase in rats after oral doses. After chronic but not acute treatment, it inhibits MAO-A and -B in the brain. Ladostigil acts like an anti-depressant in the forced swim test in rats, indicating a potential for anti-depressant activity. Ladostigil prevents the destruction of nigrostriatal neurons induced by infusion of neurotoxin MPTP in mice. The propargylamine moiety of ladostigil confers neuroprotective activity against cytotoxicity induced by ischemia and peroxynitrite in cultured neuronal cells. The multi-target iron chelator M30 has all the properties of ladostigil and similar neuroprotective activity to ladostigil, but is not a ChE inhibitor. M30 has a neurorestorative activity in post-lesion of nigrostriatal dopamine neurons in MPTP, lacatcystin and 6-hydroxydopamine animal models of PD. The neurorestorative activity is related to the ability of the drug to activate hypoxia inducing factor (HIF) which induces the production of such neurotrophins as brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF) and erythropoietin as well as glia-derived neurotrophic factor (GDNF). The unique multiple actions of ladostigil and M30 make the potentially useful drugs for the treatment of dementia with Parkinsonian-like symptoms and depression.
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Animals , Mice , Rats , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine , alpha-Synuclein , Amyloid , Hypoxia , Brain , Brain-Derived Neurotrophic Factor , Butyrylcholinesterase , Chelating Agents , Dementia , Depression , Dopamine , Erythropoietin , Ferritins , Indans , Iron , Ischemia , Models, Animal , Monoamine Oxidase , Monoamine Oxidase Inhibitors , Nerve Growth Factors , Neurons , Neuroprotective Agents , Oxidopamine , Pargyline , Peroxynitrous Acid , Propylamines , RNA, Messenger , Vascular Endothelial Growth Factor AABSTRACT
<p><b>OBJECTIVE</b>To study the derivatives of 1,2,4-triazino[5,6-b]indole-3-thione for antidepressant activity in olfactory bulbectomized (OBX) rats. Out of various derivatives tested for acute tail suspension test, the two derivatives showing prominent action were selected for bilateral olfactory bulbectomy model of chronic depression in rats.</p><p><b>METHODS</b>The sub acute effects of 14-day oral pretreatment of two derivatives labeled as 3a (70 mg/kg) and 3r (70 mg/kg), imipramine (20 mg/kg), fluoxetine (30 mg/kg) and moclobemide (15 mg/kg) were evaluated on bilateral bulbectomy induced rise in body weight, hyperphagia, hyperactivity, and on sexual dysfunction. The serum sodium concentration, body temperature, and heart rate were also recorded.</p><p><b>RESULTS</b>The derivatives 3a and 3r showed reversal of drop in body weight, reversed OBX induced hyperactivity, normalized body temperature, heart rate, and serum sodium concentration. In elevated maze test, moclobemide, 3a, 3r treatment significantly reduced time spent in open arm as compared to OBX rats. 3a and 3r also improved sexual behavior parameters.</p><p><b>CONCLUSIONS</b>The present study shows promising antidepressant action and provides a proof of concept for the chronic treatment of 3a, 3r to treat depression.</p>
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Animals , Female , Male , Rats , Acetamides , Pharmacology , Acetanilides , Pharmacology , Antidepressive Agents , Pharmacology , Behavior, Animal , Depression , Drug Therapy , Disease Models, Animal , Dose-Response Relationship, Drug , Fluoxetine , Pharmacology , Imipramine , Pharmacology , Moclobemide , Pharmacology , Olfaction Disorders , Pathology , Olfactory Bulb , General Surgery , Rats, Sprague-Dawley , Triazines , PharmacologyABSTRACT
Antidepressant, anti-inflammatory, antihypoxic and antioxidant activities of methanol extract of Juglans regia L., Juglandaceae, flower were investigated. Antidepressant activity was examined by forced swimming test and tail suspension test in mice. Antihypoxic activity was investigated in haemic and circulatory models. The effects were pronounced in both models. It produced statistically significant anti-inflammatory activity in carrageenan induced edema at nearly all doses, compared to control groups. IC50 for DPPH radical-scavenging activity was 674±27.6 µg mL-1. Extract showed good Fe2+ chelating ability (IC50 43±1.5 µg mL-1). It exhibited low antioxidant activity in linoleic acid peroxidation test. Its pharmacological effects may be attributed, in part, to the presence of phenols and ISSN 0102-695X flavonoids in the extract.
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A proposta deste trabalho foi de avaliar os efeitos da fração de alcalóides terciários totais (TTAF) de Cissampelos sympodialis Eichler (Menispermaceae) em dois modelos animais de depressão: a) teste do nado forçado e b) teste da reserpina. O tratamento de camundongos com TTAF (12,5 mg/kg) reduziu o tempo total de imobilidade dos animais. Também reverteu a hipotermia induzida por reserpina, demonstrando um efeito antidepressivo nos dois modelos. Adicionalmente, o tratamento com TTAF não modificou a ambulação e o comportamento de levantar das patas dianteiras dos animais avaliados no teste do campo aberto, realizado no intuito de investigar se a redução no tempo de imobilidade apresentada no teste do nado forçado foi causada por estimulação na atividade locomotora. Como a warifteína é um dos principais alcalóides presente na TTAF da C. sympodialis, e tem atividade inibidora da enzima fosfodiesterase, ela pode ser responsável pelo efeito antidepressivo observado na fração estudada.
The purpose of the present study was to evaluate the effects of total tertiary alkaloid fraction (TTAF) of Cissampelos sympodialis Eichler (Menispermaceae) on two animal models of depression: a) forced swim test and b) reserpine test. Treatment of mice with TTAF (12.5 mg/kg) reduced the total immobility time. It also reversed the reserpine-induced hypothermia, demonstrating an antidepressant effect in both models. Additionally, TTAF treatment did not modify the ambulation and rearing evaluated in open field test in order to investigate if the immobility time reduction found in the forced swimming test was caused by locomotive activity stimulation. Since warifteine is one of the main alkaloids present in the TTAF of C. sympodialis, and it has inhibitory activity of the phosphodiesterase enzyme, it may be responsible by the antidepressant effect found in the fraction studied.