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Antidepressant-like effect of the methanolic extract from Bupleurum falcatum in the tail suspension test

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Abstract

In traditional Oriental medicine, some herbal combinations that include Bupleurum falcatum (BFM) as a major ingredient are known to effectively treat depressive-like disorders. In the present study, the antidepressant-like effect of methanolic extract of BFM and its neuropharmacological mechanism were investigated in mice. After oral administration of BFM extract, a tail suspension test (TST) and open field test (OFT) were performed to assess the antidepressant activity and psycho-stimulant side-effects, respectively. Pre-treatment with p-chlorophenylalanine (PCPA, a serotonin synthesis inhibitor) and alpha-methyl-p-tyrosine (AMPT, a catecholamine synthesis inhibitor) was used to assess the influence of BFM extract on the antidepressant activity in the TST. At doses of 150 and 300 mg/kg body weight, p.o., the BFM extract significantly reduced the total duration of immobility in the TST, while individual differences in locomotor activities between experimental groups were not observed in the OFT. Moreover, pre-treatment with PCPA (100 mg/kg i.p., for 4 consecutive days) or AMPT (100 mg/kg i.p.) significantly inhibited the antidepressant-like activity of BFM extract (300 mg/kg p.o.), as well as we confirmed the reversal of the antidepressant effect of fluoxetine (30 mg/kg i.p.) by PCPA and bupropion (20 mg/kg i.p.) by AMPT in the TST. Taken together, these findings suggest that the methanolic BFM extract has dose-dependent possibility of antidepressant-like activity valuable to alternative therapy for depression and that the mechanism of action involves the serotonergic and noradrenergic systems although underlying mechanism still remains to be further elucidated.

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... After realizing the importance of serotonergic neurotransmission in the pharmacological effects of the active compounds, we tried to clarify possible serotonergic receptors participating the mechanism of action. Therefore, probable contributions of 5-HT1A, 5-HT2A/2C and 5-HT3 serotonergic receptors to the observed antidepressant-like effects were evaluated by pre-treatments with NAN-190, ketanserin and ondansetron, respectively [54,55]. ...
... After realizing the importance of serotonergic neurotransmission in the pharmacological effects of the active compounds, we tried to clarify possible serotonergic receptors participating the mechanism of action. Therefore, probable contributions of 5-HT 1A , 5-HT 2A/2C and 5-HT 3 serotonergic receptors to the observed antidepressant-like effects were evaluated by pre-treatments with NAN-190, ketanserin and ondansetron, respectively [54,55]. ...
... PCPA was intraperitoneally administered at dose of 100 mg/kg for four consecutive days. Test compounds were applied 24 h after the last injection and 1 h later, animals were subjected to the TST [54]. NAN-190 (0.5 mg/kg i.p.), ketanserin (1 mg/kg i.p.), ondansetron (0.3 mg/kg i.p.) were injected 15 min prior to the administration of the test compounds. ...
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Novel benzazole derivative compounds 4a–4h were obtained by the reaction of corresponding 2-(benzazol-2-ylthio)acetohydrazide and appropriate 4-substituted benzaldehydes. The chemical structures of the synthesized compounds were elucidated by FT-IR, 1H-NMR, 13C-NMR and LCMS spectroscopic methods. Antidepressant-like effects of the compounds were evaluated by tail suspension test (TST) and modified forced swimming tests (MFST). Moreover, locomotor activities of the animals were assessed by an activity cage apparatus. In the series, compounds 4a, 4b, 4e and 4f (at 50 mg/kg) significantly decreased the immobility time of mice in both of the TST and MFST. The same compounds prolonged the swimming time of animals in MFST without any change in the climbing duration. These data indicated that compounds 4a, 4b, 4e and 4f possess significant antidepressant-like activities. Moreover, pre-treatments with p-chloro-phenylalanine methyl ester (an inhibitor of serotonin synthesis), NAN-190 (a 5-HT1A antagonist), ketanserin (a 5-HT2A/2C antagonist), and ondansetron (a 5-HT3 antagonist) reversed the exhibited pharmacological effects. Results of the mechanistic studies suggested the involvement of serotonergic system and contributions of 5-HT1A, 5-HT2A/2C and 5-HT3 receptors to the antidepressant-like effects of compounds 4a, 4b, 4e and 4f. Furthermore, unchanged locomotor activity of mice following the administrations of these four derivatives confirmed that the presented antidepressant-like effects are specific.
... Mechanistic studies were carried out with PCPA (serotonin synthesis inhibitor, 100 mg/kg, i.p., for 4 consecutive days) and AMPT (catecholamine synthesis inhibitor, 100 mg/kg, i.p., 4 h before vehicle or tofisopam administration) (Kwon et al., 2010) in order to investigate the possible involvement of the serotonergic and catecholaminergic systems in the tofisopam-induced antidepressant-like effects, respectively (Can et al., 2017). Moreover, the potential contribution of the opioid system was clarified using specific opioid receptor subtype antagonist compounds. ...
... AMPT pretreatment (100 mg/kg) has been reported to reduce norepinephrine and dopamine levels by 53% and 57%, respectively, in the brains of mice without affecting serotonin levels (Mayorga et al., 2001;Widerlöv and Lewander, 1978). In this study, AMPT pretreatments did not alter the immobility time of control animals in parallel with the results of the previous studies (Bevilaqua et al., 2016;Can et al., 2013Can et al., , 2017Kwon et al., 2010;Pałucha-Poniewiera et al., 2017). However, it abolished the anti-immobility effect of tofisopam in the TST (Figure 3(b)), indicating that the catecholaminergic system, together with the serotonergic system, mediates the antidepressant-like effect of the drug. ...
Article
Background Depression is a disease that affects millions of people worldwide, and the discovery and development of effective and safe antidepressant drugs is one of the important topics of psychopharmacology. Objectives In this study, it was aimed to investigate the antidepressant-like activity potential of tofisopam, an anxiolytic drug with 2,3-benzodiazepine structure, and to elucidate the pharmacological mechanisms mediating this effect. Methods The antidepressant-like activity of tofisopam was investigated using tail suspension and modified forced swimming tests. Possible interactions of tofisopam with µ- and δ-opioid receptor subtypes were clarified by pharmacological antagonism, molecular docking and molecular dynamics simulation studies. Results Tofisopam (50 and 100 mg/kg) significantly shortened the immobility time of mice in both the tail suspension and the modified forced swimming tests. The drug, at the same doses, prolonged the duration of swimming and climbing behaviours measured in modified forced swimming tests. A dosage of 25 mg/kg was ineffective. Mechanistic studies showed that the pretreatment with p-chlorophenylalanine methyl ester (serotonin synthesis inhibitor; 4 consecutive days, 100 mg/kg), α-methyl-para-tyrosine methyl ester (catecholamine synthesis inhibitor; 100 mg/kg), naloxonazine (selective µ-opioid receptor blocker, 7 mg/kg) and naltrindole (a selective δ-opioid receptor blocker, 0.99 mg/kg) abolished the anti-immobility effect induced by the 50 mg/kg dose of tofisopam in the tail suspension tests. Our in silico studies supported the behavioural findings that the antidepressant-like effect of tofisopam is mediated by μ- and δ-opioid receptors. Conclusion This study is the first to show that tofisopam has antidepressant-like activity mediated by the serotonergic, catecholaminergic and opioidergic systems.
... Depression is a heterogeneous disorder that often manifests with various symptoms at the psychological, behavioural, and physiologic levels. 1 Although treatment with commercially available antidepressant drugs is effective, a significant number of patients do not achieve continuous remission, despite intensive management, and only 60% of patients are responsive to currently available antidepressants. 2 The most common adverse effects of these antidepressants include agitation, nausea, headache, sleeplessness or drowsiness, and sexual problems. The impulsive clinical response to antidepressant drugs and high susceptibility to adverse effects are major clinical problems 3 thus, novel therapeutic agents are still needed to treat depression. ...
... 33 Therefore, OFT was used to exclude these false effects that could be associated with psychostimulants, convulsants, and anticholinergics or hyperkinesis. 2 The main difference between antidepressants and psychostimulants is that antidepressants would not increase locomotor activity. 34 In addition, the finding suggested that the reduction of immobility time elicited by the methanol extract in the FST as well as in the TST was a specific result of its antidepressant mechanism. ...
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Objectives: The present study aims to assess the antidepressant activity of Ixora coccinea extracts in mice and phytochemical analysis of the active extract by GC-MS. Materials and methods: After oral administration of extracts, tail suspension test (TST), force swim tests (FST), and open field tests (OFT) were performed to assess the antidepressant activity. GC-MS analysis of methanol extract of I. coccinea was performed to ascertain the chemical constituents in the bioactive extract. Results: The methanol extract of I. coccinea at dose of 100 and 200 mg/kg body weight, p.o. significantly reduced the total duration of immobility in the TST as well as FST (p<0.01). I. coccinea extracts showed no significant changes in locomotor activity in OFT. Conclusion: The methanol extract of I. coccinea possesses antidepressant-like properties in mice with no significant effect on locomotor activity in OFT.
... The method to obtain methanol, ethanol, acetone and ethyl acetate extracts is reflux extraction (You et al. 2002;Cheng et al. 2005;Lee et al. 2010;Liu et al. 2014a). To obtain methanol extracts, Radix Bupleuri is extracted twice by 100% methanol or 95% methanol with 5% pyridine at 70 C for 4 h (Xie et al. 2006;Kwon et al. 2010;Nakahara et al. 2011;Liu et al. 2014a;Ashour et al. 2014). To obtain ethanol extracts, Radix Bupleuri is extracted twice by 60% , 70% or 80% ethanol (Lee et al. 2012a) at room temperature for 6 h. ...
... Both ethanol extracts and methanol extracts of B. falcatum have an anti-inflammatory effect Nakahara et al. 2011) with similar mechanisms to SSa. They also possess an antidepressant activity possibly through central adrenergic mechanism (Kwon et al. 2010;Lee et al. 2012a). Besides, the ethanol extracts of B. falcatum has its specific memory improvement activity by attenuating immobilization (IMO) stress-induced loss of cholinergic immunoreactivity in the hippocampus (Lee et al. 2009). ...
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Context: Radix Bupleuri has been used in traditional Chinese medicine for over 2000 years with functions of relieving exterior syndrome, clearing heat, regulating liver-qi, and lifting yang-qi. More natural active compounds, especially saikosaponins, have been isolated from Radix Bupleuri, which possess various valuable pharmacological activities. Objective: To summarize the current knowledge on pharmacological activities, mechanisms and applications of extracts and saikosaponins isolated from Radix Bupleuri, and obtain new insights for further research and development of Radix Bupleuri. Methods: PubMed, Web of Science, Science Direct, Research Gate, Academic Journals and Google Scholar were used as information sources through the inclusion of the search terms ‘Radix Bupleuri’, ‘Bupleurum’, ‘saikosaponins’, ‘Radix Bupleuri preparation’, and their combinations, mainly from the year 2008 to 2016 without language restriction. Clinical preparations containing Radix Bupleuri were collected from official website of China Food and Drug Administration (CFDA). Results and conclusion: 296 papers were searched and 128 papers were reviewed. A broad spectrum of in vitro and in vivo research has proved that Radix Bupleuri extracts, saikosaponin a, saikosaponin d, saikosaponin c, and saikosaponin b2, exhibit evident anti-inflammatory, antitumor, antiviral, anti-allergic, immunoregulation, and neuroregulation activities mainly through NF-κB, MAPK or other pathways. 15 clinical preparations approved by CFDA remarkably broaden the application of Radix Bupleuri. The main side effect of Radix Bupleuri is liver damage when the dosage is excess, which indicates that the maximum tolerated dose is critical for clinical use of Radix Bupleuri extract and purified compounds.
... After exposure to SPS, SIL (25,50, and 100 mg/kg, SIL; Sigma-Aldrich Chemical Co., St. Louise, MO, USA) and fluoxetine hydrochloride (10 mg/kg, FLX, Sigma) were intraperitoneally injected daily for 14 days. The control group without SPS exposure and SPS-induced only rats were intraperitoneally administered with saline at the same volume. ...
... Before completion of the FST trial, rats were exposed to the open field test (OFT) as previously described [25]. To determine the difference in activity between SPS exposure and each drug treatment, various behaviors in the open field were observed. ...
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Background: Post-traumatic stress disorder (PTSD) is an extreme mood disorder that occurs after experiencing extreme stress, and patients with this disorder are known to accompany with symptoms of depression, anxiety, and memory impairments. Silibinin (SIL) is a natural polyphenolic flavonoid and is the main active ingredient of silymarin, which is primarily extracted from the milk thistle. Although some studies have assessed the properties of this flavonoid, the potential of SIL as a treatment for PTSD patients and its mechanisms of action have yet to be fully elucidated. Methods: After exposure to a model of single prolonged stress (SPS), the open field test (OFT) and forced swimming test (FST), were used to investigate the effects of SIL on anxiety- and depression-like symptoms in male rats. The rats received of SIL (25, 50, and 100 mg/kg) for 14 days following exposure to SPS. Results: Administration of SIL significantly improved anxiety-like behaviors in the OFT, depression-like behaviors in the FST, and freezing behavior in fear conditioning test. SIL also increased levels of serotonin in the hippocampus (Hipp) and amygdala, and enhanced expression of tryptophan hydroxylase-1 mRNA in the Hipp. The administration of SIL also inhibited SPS-induced decreases dopamine levels and increases norepinephrine levels in the Hipp. Conclusions: Taken together, the present findings suggest that SIL can be a useful therapeutic ingredient for the treatment of trauma stress-associated symptoms, including PTSD-induced anxiety and depression caused by PTSD.
... Recent theories suggest that monoamines act only as regulator to other more important brain neurobiological systems [13]. The traditional therapeutic strategy is the only current treatment that affects serotonin and norepinephrine system, but approximately half of affected people are insufficiently cured by psychotherapeutic approaches and existing medication [14,15]. There is no success in developing fundamentally new antidepressants with distinct mechanisms of action despite remarkable efforts [16]. ...
... The TST is widely used for screening new antidepressant drugs and for elucidation of their mechanism (s) of action [26]. The TST is also known to be highly sensitive to the major classes of antidepressants, including the selective serotonin reuptake inhibitors (SSRIs), the tricyclic antidepressants (TCAs), and the monoamine oxidase inhibitors (MAOIs) [26,27]. Thus, the more sensitive method than the FST was used to investigate the likely mechanism(s) of action involved in the antidepressant-like effect of MJ. ...
Article
Purpose: The efficacy of current antidepressant drugs has been compromised by adverse effects, low remission and delay onset of action necessitating the search for alternative agents. Methyl jasmonate (MJ), a bioactive compound isolated from Jasminum grandiflorum has been shown to demonstrate antidepressant activity but its mechanism of action remains unknown. Thus, the role of monoaminergic systems in the antidepression-like activity of MJ was investigated in this study. Materials and methods: Mice were given i.p. injection of MJ (5, 10 and 20mg/kg), imipramine (10mg/kg) and vehicle (10mL/kg) 30min before the forced swim test (FST) and tail suspension test (TST) were carried out. The involvement of monoaminergic systems in the anti-depressant-like effect of MJ (20mg/kg) was evaluated using p-chlorophenylalanine (pCPA), metergoline, yohimbine, prazosin, sulpiride and haloperidol in the TST. Results: MJ significantly decrease the duration of immobility in the FST and TST relative to control suggesting antidepressant-like property. However, pretreatment with yohimbine (1mg/kg, i.p., an α2-adrenergic receptor antagonist) or prazosin (62.5μg/kg, i.p., an α1-adrenoceptor antagonist) attenuated the antidepressant-like activity of MJ. Also, pCPA; an inhibitor of serotonin biosynthesis (100mg/kg, i.p) or metergoline (4mg/kg, i.p., 5-HT2 receptor antagonist) reversed the anti-immobility effect of MJ. Sulpiride (50mg/kg, i.p., a D2 receptor antagonist) or haloperidol (0.2mg/kg, i.p., a dopamine receptor antagonist) reversed the anti-immobility effect of MJ. Conclusion: The results of this study suggest that serotonergic, noradrenergic and dopaminergic systems may play a role in the antidepressant-like activity of MJ.
... For AMPT (100 mg/kg, i.p.) studies, mice were pre-treated with AMPT or vehicle (saline with 10% Tween 80) 4 h prior the administration of physiological saline or gallic acid. Sixty min later they were tested in the TST [53,54]. For further antagonistic studies, in different experimental groups, mice were pre-treated with phentolamine (5 mg/kg, i.p.) [55], propranolol (5 mg/kg, i.p.) [56], SCH 23390 (0.05 mg/kg, s.c.) [57], sulpiride (50 mg/kg, i.p.) [58], or vehicle (saline) 15 min prior to the saline or gallic acid treatments. ...
Article
Aims: This study was planned to examine the antidepressant potency of gallic acid (30 and 60 mg/kg), a phenolic acid widely distributed in nature, together with its possible underlying monoaminergic mechanisms. Main methods: Antidepressant-like activity was assessed using the tail suspension (TST) and the modified forced swimming tests (MFST). Locomotor activity was evaluated in an activity cage. Key findings: Administration of gallic acid at 60mg/kg reduced the immobility duration of mice in both the TST and MFST without any changes in the locomotor activity. The anti-immobility effect observed in the TST was abolished with pre-treatment of p-chlorophenylalanine methyl ester (an inhibitor of serotonin synthesis; 100mg/kg i.p. administered for 4-consecutive days), ketanserin (a 5-HT2A/2C antagonist; 5mg/kg i.p.), ondansetron (a 5-HT3 antagonist; 0.3mg/kg i.p.), α-methyl-para-tyrosine methyl ester (an inhibitor of catecholamine synthesis; 100mg/kg i.p.), phentolamine (non-selective alpha-adrenoceptor antagonist; 5mg/kg i.p.), SCH 23390 (a dopamine D1 antagonist; 0.05mg/kg s.c.), and sulpiride (a dopamine D2/D3 antagonist; 50mg/kg i.p.). However, NAN 190 (a 5-HT1A antagonist; 0.5mg/kg i.p.) and propranolol (a non-selective β-adrenoceptor antagonist; 2mg/kg i.p.) pre-treatments were ineffective at reversing the antidepressant-like effects of gallic acid. Significance: The results of the present study indicate that gallic acid seems to have a dual mechanism of action by increasing not only serotonin but also catecholamine levels in synaptic clefts of the central nervous system. Further alpha adrenergic, 5-HT2A/2C and 5-HT3 serotonergic, and D1, D2, and D3 dopaminergic receptors also seem to be involved in this antidepressant-like activity.
... Different ethno-pharmaceutical properties of various plant extracts and their effects are summarised in Table 7. Behavioural Despair [47] Allium sativum Garlic Rhizome Ethanolic Extract, dose25,50 and 100 mg/kg [48] Aloysia polystachya Lemon Verbena Aerial Part Hydroethanolic Extract Effect on Depression [49] Apocynum venetum Dogbane Aerial Part Dose-30-125 mg/kg [50] Areca catechu Betel Nut Fruit Ethanolic Extract, dose4-80 mg/kg Effect on Motor Activity [51] Asparagus racemosus Satavari Root Methanolic Extract, dose-100,200 and 400 mg/kg Effect on Serotonergic And Noradrenergic System And Augmentation Of Antioxidant Defences [52] Bacoba monnieri Brahmi Aerial Part Methanolic Extract, dose-20 and 40 mg/kg Significant Antioxidant Effect, Anxiolytic Activity And Improve Memory Retention [53] Berberis aristata Indian Barberry Root Berberine, (An Alkaloid), dose-5,10 and 20 mg/kg. Effect on CNS, Inhibit Monoamine Oxidase-A [54] Bupleurum falcatum Chai Hu, Hare's Ear Root Root Methanolic Extract Psycho stimulant Effect [55] Cimicifuga racemosa Black Bugbane Roots And Rhizomes Ethanolic And Isopropanolic Aqueous Extracts Effect on heraprutical Responses In Climacteric Women [56] Citation: Khushboo, Sharma B (2017) Antidepressants: Mechanism of Action, Toxicity and Possible Amelioration. J Appl Biotechnol Bioeng 3(5): 00082. ...
... In general, hyperkinesis also produces false positive effect in immobility time (Freitas et al., 2010). Therefore, open field test was carried out to justify false positive effects that could be associated with psychostimulants, convulsants and anticholinergics or hyperkinesis (Kwon et al., 2010). The antidepressants would not affect on locomotor activity (Borsini and Meli, 1988). ...
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p class="Abstract">Hamelia patens is used in folk medicine in the treatment of nervous shock. The present study deals to evaluate the antidepressant-like effects of chloroform and methanol extracts of H. patens on the performance of male mice and GC-MS profiling of bioactive extract. Mice were given extracts orally in acute doses of 100 and 200 mg/kg daily for 7 days and then subjected to forced swim test, tail suspension test and open field test. Imipramine (10 mg/kg/day, p.o.) and fluxetamine (10 mg/kg/day, p.o.) were used as the standard in forced swim test and tail suspension test respectively. GC-MS profiling of chloroform extract was performed to find out the chemical constituents in bioactive fraction. After one-week treatment, the chloroform extract (100 and 200 mg/kg/day, p.o.) significantly reduced immobility time in forced swim test and tail suspension test (p<0.05). All extracts did not show any significant change in the locomotor activity in open field test. These data indicate that the extract of H. patens possesses antidepressant-like properties in mice without any significant effect on locomotor activity. Video Clip of Methodology : 4 min 06 sec: Full Screen Alternate </p
... Thus, we assume that chrysin may act by modulating the levels of 5HT and dopamine. It is well known that monoamines play an important role in depression (Liang et al., 2016;Sarris et al., 2011;Kwon et al., 2010). For example, 5HT is an important neurotransmitter in depression states, and a dysfunctional 5HT system is generally regarded as a risk factor for depression (Han et al., 2015). ...
Article
Hypothyroidism is often associated with psychiatric disorders such as depression. In this study, we evaluated the effect of chrysin on depressive-like behavior and monoamine levels in hypothyroid female mice. Hypothyroidism was induced by continuous exposure to 0.1% methimazole (MTZ) in drinking water for 31 days. Exposure to MTZ was associated with low plasma levels of thyroid hormones T3 and T4 compared with the control group. Subsequently, euthyroid and MTZ-induced hypothyroid mice were intragastrically administered vehicle or chrysin (20mg/kg) once a day for 28 consecutive days. After treatments, the following behavioral assessments were performed: Open-Field Test (OFT), Tail suspension test (TST), and Forced Swimming Test (FST). Additionally, T3 and T4 levels were measured again, and serotonin (5HT), dopamine, and noradrenaline levels were analyzed in the prefrontal cortex and the hippocampus. Chrysin treatment could not reverse T3 and T4 levels. Hypothyroid mice showed an increased immobility time in TST and FST; chrysin treatment reversed these effects. Reduced levels of 5HT and dopamine in the prefrontal cortex and the hippocampus were observed in the hypothyroid mice than in the euthyroid mice. Chrysin treatment recovered 5HT content in both structures and dopamine content only in the hippocampus. Noradrenaline content was not altered by treatments. Together, our results have demonstrated that chrysin treatment reverses depressive-like behaviors in hypothyroid female mice and suggests the involvement of 5HT and dopamine in these effects.
... Total SSs extracted from RB can reverse the chronic mild stress-induced diminished expression of monoamine neurotransmitter concentrations (5-HT, DA and NE) in the prefrontal cortex (Sun et al., 2012). Similarly, Sunoh et al. found that RB extract significantly reduces the total duration of immobility in a tail suspension test and exerted an antidepressant activity in mouse model (Kwon et al., 2010). A recent study further confirmed that 4-week administration of SSa attenuates perimenopausal depression-like symptoms induced by chronic unpredictable mild stress by restoring the dysregulation of hypothalamic-pituitaryadrenal (HPA) axis, reducing neuroinflammation and promoting brainderived neurotrophic factor (BDNF)-TrkB signaling in the hippocampus . ...
... Each group consisted of ten mice: Control group (Ctrl) received DMSO as a vehicle, Fluoxetine group (30 mg/kg) (Flx) was used as positive control [29]. The remaining groups received the different compounds. ...
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• Background: Pyrroles and fused pyrroles are of great interest as biologically active compounds, among these activities; antidepressant activity is of special concern. Objective: Synthesis of a series of pyrrolopyrazoles and their pyrimidine derivatives and their characterization using spectral data to be monitored for antidepressant activity using behavioral techniques. Method: A control group provided by the vehicle i.p., positive control group received fluoxetine as standard and all other groups were administered the tested compounds. The groups were subjected to tail suspension test (TST) to determine the antidepressant activity compared with fluoxetine as standard drug. The compounds exhibiting antidepressant activity were then used to analyze changes in serotonin (5HT) level in the brain of albino mice. Results: TST results showed that both [pyrazoles & pyrazlopyrimidines] derivatives exhibit promising anti-depressant activity. Conclusion compounds [pyrazoles & pyrazlopyrimidines] show promising antidepressant activity possibly mediated by the increased levels of 5HT.
... The OFT was carried out before the FST to avoid false-positive or negative outcomes induced by stimulatory effects of treatments in the antidepressant evaluation. [26] The OFT is a model commonly employed to measure exploratory behavior and general activity in rodents. [27] Based on the OFT, no significant alterations in behavior or locomotor activity of the extract or fractions of H. juniperinum were observed compared with the control. ...
Article
Background: Some members of the genus Hypericum have been shown to demonstrate antidepressant-like effects. In Colombia, approximately 54 species of Hypericum have been reported, and only a few have been investigated chemical and pharmacologically. Objective: The aim of this study was to evaluate the antidepressant-like effects of a methanol extract, as well as ethyl acetate and butanol fractions, obtained from aerial parts of Hypericum juniperinum K. Materials and Methods: Behavioral and locomotor activities were evaluated in the open field test (OFT). Antidepressant-like activity was measured in the forced swimming test (FST) in male Swiss albino mice. Preliminary phytochemical screening as well as a high-performance liquid chromatography (HPLC) profile of the active fractions of H. juniperinum was performed. Results: Treatment with the methanol extract at 500 mg/kg and the ethyl acetate and butanol fractions at 150 and 300 mg/kg resulted in a decrease in the immobility times in FST. In the OFT, none of the treatments presented altered behavior or locomotor activity of mice. Preliminary phytochemical screening identified terpenes/steroids, flavonoids, phenol derivatives, tannins, and saponins. In the HPLC analysis of the fractions, rutin, quercitrin, and quercetin were identified with the help of coinjection of standards. Conclusion: This is the first report of the antidepressant-like activity of extracts and fractions obtained from H. juniperinum in the FST model of depression. Flavonoids may be responsible for the antidepressant-like action of H. juniperinum. Abbreviations used: FST: Forced swimming test; HJE: Methanol extract of Hypericum juniperinum; HJEAF: Ethyl acetate fraction obtained from the methanol extract of Hypericum juniperinum; HJEBF: Butanol fraction obtained from the methanol extract of Hypericum juniperinum; HPE: Methanol extract of Hypericum perforatum; HPLC: High-performance liquid chromatography; IMI: Imipramine; MeOH: Methanol; OFT: Open field test; tR: Retention time; UV: Ultra violet; VEH: Vehicle.
... According to previous studies, Bupleuri Radix has neuroprotective effects and can be used to treat asthma and gastric ulcers (Sun et al., 1991;Park et al., 2002;Lee et al., 2009;Kwon et al., 2010). Moreover, kamishoyo-san, including Bupleuri Radix, is effective at treating tremors due to antipsychotic-induced Parkinsonism, and yokukansan, including Bupleuri Radix, improves the behavioral and psychological symptoms of dementia in patients with PD (Ishikawa et al., 2000;Kawanabe et al., 2010). ...
Article
Parkinson’s disease (PD) is one of the progressive neurodegenerative diseases of whose condition is characterized by dopaminergic neuronal cell loss and dysfunction in the substantia nigra pars compacta (SNpc) and the striatum (ST). Recent studies have demonstrated that the nuclear receptor related-1 protein (Nurr1) is critical of dopaminergic phenotype induction in mesencephalic dopaminergic neurons. Further, Nurr1 engages in synthesizing and storing dopamine through regulating levels of tyrosine hydroxylase (TH), dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2). The aim of this study was to investigate the protective effects of an herbal extract combination, consisting of Bupleurum falcatum, Paeonia suffruticosa, and Angelica dahurica (MABH), on 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD-like symptoms and to elucidate possible mechanisms of action focusing on Nurr1. In a subacute mouse model of MPTP-induced PD, MABH treatment resulted in recovery from movement impairments. MABH prevented dopamine depletion and protected against dopaminergic neuronal degradation induced by MPTP. Additionally, MABH increased Nurr1 expression in the SNpc of mice. To evaluate the effects of MABH on Nurr1 expression, we measured the protein levels of Nurr1 and its regulating factors using Western blot analysis in PC12 cells. MABH treatment induced the phosphorylation of extracellular signal-regulated kinase (ERK) protein via increasing the protein expression levels of Nurr1 and ultimately the levels of TH, VMAT2, and DAT. These results indicate that MABH has protective effects on dopaminergic neurons in a mouse model of PD by regulating Nurr1.
... posed of Adix Bupleuri (Chai Hu), Chinese Angelica and White Peony Root (Bai Shao), which plays the main role in whole formula. Adix Bupleuri (ChaiHu) contributes to Soothing liver and relieving depression, the experiment stated that the methanolic Bupleurum falcatum (BFM) extract had dose-dependent possibility of antidepressant-like activity valuable to alternative therapy for depression and that the mechanism of action might involve the serotonergic and noradrenergic systems[33]. Chinese Angelica (Dang Gui) can be used for tonifying and harmonizing blood, regulating menstruation to relieve pain. ...
... Agents like amphetamine and anticholinergic which enhance locomotors activity or cause hyperkinesias in Open Field Test (OFT) to produce false positive results in FST and TST [13]. Hence the need of OFT as a paradigm to eliminate the bias that anti-immobility effect could be associated with hyperkinesias [14]. The observation that VA did not increase the number of lines crossed in the open field test eliminates exertion of psycho-stimulant-like action and confirms the assumption that antidepressant-like effect of the extract in the TST and FST is specific. ...
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Vernonia amygdalina commonly called bitter leaf, belongs to the family Astaraceae, and has been reported to be used locally in the treatment of psychiatric challenges. However, dearth work has been reported on anxiety and no work has been reported on depression. This study was therefore designed to investigate the antidepressant activities of Vernonia amygdalina and its probable mechanism of activities in mice. The antidepressant-like potentials of VA (50-200mg/kg) was explored in Forced Swimming Test (FST), Tail Suspension Test (TST), reserpine-induced models and Open Field Test (OFT). Mice were pre-treated with graded doses VA (50-200 mg/kg) and imipramine (60mg/kg). And, also mice were pre-treated with monoamine receptor blockers: metergoline (5-HT 2), prazosin (alpha-1-adrenoceptor) and sulpiride (D 2) before VA (100mg/kg) was administered to elucidate the mechanisms involved in it antidepressant-like effects using the TST. Vernonia amygdalina (100mg/kg and 200mg/kg) were found to be significantly increase mobility as when compared with control in FST and TST model. 100mg/kg and 200 mg/kg of VA reduced the ptosis in reserpine-induced depression and 200 mg/kg of VA was able to increase the temperature in mice in reserpine-induced depression. VA was seen to be mediated through alpha-1-adrenergic receptor, dopamine D 2 receptor and 5-HT 2 receptor as there was significant increase immobility when compared to 100 mg/kg of VA. This study showed that Vernonia maygdalina may possess antidepressant-like effects in FST, TST and reserpine-induced depression models which may be mediated through serotonergic, nor-adrenergic and dopaminergic system.
... Moreover, many neurochemicals comprise the stress response system, including norepinephrine, serotonin, and -aminobutyric acid [43]. In addition, the methanolic extract from Bupleurum falcatum, derived from Xiaoyaosan, has dose-dependent antidepressant-like activity and the serotonergic and noradrenergic systems may act as the targets [44]. However, as the components are very complicated, the analysis and assessment of the disassembled prescription deserve further research. ...
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Background. Compared with antidepressant activity of Xiaoyaosan, the role of Xiaoyaosan in anxiety has been poorly studied. Objective. To observe the effects of Xiaoyaosan on anxiety-like behavior induced by chronic immobilization stress (CIS) and further explore whether these effects were related to CRF1R signaling. Methods. Adult male SD rats were randomly assigned to five groups ( n = 12 ): the nonstressed control group, vehicle-treated (saline, p.o.) group, Xiaoyaosan-treated (3.854 g/kg, p.o.) group, vehicle-treated (surgery) group, and antalarmin-treated (surgery) group. Artificial cerebrospinal fluid (0.5 μL/side) or CRF1R antagonist antalarmin (125 ng/0.5 μL, 0.5 μL/side) was bilaterally administered into the basolateral amygdala in the surgery groups. Except for the nonstressed control group, the other four groups were exposed to CIS (14 days, 3 h/day) 30 minutes after treatment. On days 15 and 16, all animals were subjected to the elevated plus-maze (EPM) and novelty suppressed feeding (NSF) test. We then examined the expression of CRF1R, pCREB, and BDNF in the amygdala. Results. Chronic pretreatment with Xiaoyaosan or antalarmin significantly reversed elevated anxiety-like behavior and the upregulated level of CRF1R and BDNF in the amygdala of stressed rats. pCREB did not differ significantly among the groups. Conclusions. These results suggest that Xiaoyaosan exerts anxiolytic-like effects in behavioral tests and the effects may be related to CRF1R signaling in the amygdala.
... Researchers have sought potential sources of practical and rapid-onset antidepressants (Wattanathorn, Pangpookiew, Sripanidkulchai, Muchimapura & Sripanidkuchai, 2007;Hashimoto, 2019;Kraus et al., 2019). Some of the identified sources of potential antidepressants are plant products (Shi & Wang, 2006;Freitas et al., 2010;Kwon et al., 2010;Lee et al., 2010;Wang et al., 2010). Trichilia monadelpha is a traditional medicinal plant commonly used to manage various neurological disorders, including depression (No Author, 1927;Shin et al., 2014;Kukuia et al., 2018). ...
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Introduction: Major depressive disorder is often associated with suicidal tendencies, and this condition accentuates the need for rapid-acting antidepressants. We previously reported that Alkaloids (ALK) from Trichilia monadelpha possess antidepressant action in acute animal models of depression and that this effect is mediated through the monoamine and L-arginine-NO-cGMP pathways. This study investigated the possible rapid-onset antidepressant effect of ALK from T. monadelpha and its connection with the glycine/NMDA receptor pathway. Methods: The onset of ALK action from T. monadelpha was evaluated using the Open Space Swim Test (OSST), a chronic model of depression. The modified forced swimming and tail suspension tests were used to assess the effect of the ALK on the glycine/NMDA receptor pathway. The Instutute of Cancer Research (ICR) mice were treated with either ALK (30-300 mg/kg, orally [PO]), imipramine (3-30 mg/kg, PO), fluoxetine (3-30 mg/kg, PO), or saline. To identify the role of glycine/NMDA receptor pathway in the effect of ALK, we pretreated mice with a partial agonist of the glycine/NMDA receptor, D-cycloserine (2.5 mg/kg, intraperitoneally [IP]), and an agonist of glycine/NMDA receptor, D-serine (600 mg/kg, IP), before ALK administration. Results: ALK reversed immobility in mice after the second day of drug treatment in the OSST. In contrast, there was a delay in the effects induced by fluoxetine and imipramine. ALK also increased mean swimming and climbing scores in mice. ALK was more efficacious than imipramine and fluoxetine in reducing immobility and increasing distance traveled. It is noteworthy that ALK was less potent than fluoxetine and imipramine. D-cycloserine potentiated mobility observed in the ALK- and fluoxetine-treated mice. In contrast, D-serine decreased mobility in the ALK-treated mice. Conclusion: The study results suggest that ALK from T. monadelpha exhibits rapid antidepressant action in mice, and the glycine/NMDA receptor pathway possibly mediates the observed effect.
... ?>Thus, the effects of KKT on consummatory anhedonia in aged mice may have commonalities with the aforementioned typical antidepressants. It is noteworthy that chronic treatment with BR extract results in antidepressant-like effects in immobility time in the tail suspension test via the activation of serotonergic and noradrenergic systems, implying pharmacological similarity between KKT and typical antidepressants (Kwon et al., 2010). ...
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The cognitive and psychological domains of frailty in the elderly have drawn increasing attention given the aging of society. However, therapeutics to treat minor deficits in cognition and mental state in the elderly remain an unmet need. Kamikihito (KKT), a traditional Japanese Kampo medicine indicated for neuroses, anxiety, and insomnia, is effective for treating cognitive dysfunction and depressive-like behaviors in animal models, suggesting that it may have therapeutic potential for treating cognitive and/or mental frailty. In this study, we first validated the known anxiolytic effects of KKT in a conventional maze test. We then introduced an automated behavioral assay system, IntelliCage, to evaluate the therapeutic potential of KKT for age-related and diverse central functions by performing sequential behavioral tasks in young and aged mice to assess basal activities, cognitive functions, perseveration, and hedonic-related behaviors. Although young mice treated with KKT did not exhibit changes in diurnal variation, KKT-administered aged mice exhibited an accelerated decline in voluntary activity during the early part of the light period, implying that KKT may promote sleep onset in aged mice. Neither place learning acquisition for gaining rewards nor subsequent behavioral flexibility performance was altered by KKT in the young group, whereas the aged KKT group exhibited significantly enhanced performance in both phases of learning relative to age-matched controls. Conversely, perseverative nose-pokes (NPs) to gain rewards observed during place learning, indicative of compulsivity, were attenuated by KKT in both age groups. Regarding hedonic processing, aged mice exhibited a decreased preference for sweet solutions compared to young mice, which was effectively reversed by KKT treatment. Furthermore, KKT elevated high-effort choices for high-value reward in an effort-based decision-making paradigm in both age groups, implying augmentation of motivational behaviors by KKT. Collectively, KKT exerted various beneficial effects in cognitive and emotional domains, several of which were more evident in aged mice than in young mice, suggesting the potential of KKT for treating cognitive and mental frailty.
... Radix Bupleuri is another monarch ingredient in SYC, which may affect the quality of prescriptions significantly. Bupleuri Radix, or prescriptions containing Bupleuri Radix as the major component, for example Xiaochaihutang, exert antidepressant-like effects by modulating serotonergic and noradrenergic systems in brain regions of rat models of depression (4,5). Our previous studies also revealed antidepressant-like effects of ethanol extracts from Paeonia lactiflora Radix and Bupleuri Radix (6). ...
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The Chinese herbal formula, Shu-Yu capsule (SYC), has been successfully used to treat depression-like disorders in clinical settings. To rapidly identify the chemical constituents of SYC and its metabolites in rat serum, a simple and sensitive liquid chromatography-tandem mass spectrometry method was established in the present study. By comparing the retention times, MS and MSn spectra data in the literature and reference standards, a total of 73 compounds were identified from SYC. In rat serum, 62 components, including 13 prototype compounds and 49 metabolites were identified. Of these components, 14 metabolites were confirmed as novel metabolites of SYC. The results of the present study indicated that certain flavonoid glycosides and monoterpene glycosides were absorbed directly. Glucuronidation and sulfation were identified as the predominant metabolic pathways of the components in SYC. In addition, certain phase I reactions, including hydrolysis, demethylation and hydroxylation occurred in the rats. These results provide scientific evidence, which support further investigations of the pharmacology and mechanism of SYC.
... Bupleurum falcatum reduced the total duration of immobility in mice in the TST with no modification observed in the OFT. The activity was dose-dependent and involved the serotonergic and noradrenergic systems [95]. In addition, it significantly reduced depression-like symptoms following repeated restraint stress through hypothalamic CRF modulation and noradrenergic system regulation in the locus coeruleus of treated rats [96]. ...
Article
Medicinal plants and their extracts are natural remedies with enormous potential for treating various diseases, including depression and anxiety. In the case of depression, hundreds of plants have traditionally been used in folk medicine for generations. Different plant extracts and natural products have been analyzed as potential antidepressant agents with validated models to test for antidepressant-like effects in animals, although other complementary studies have also been employed. Most of these studies focus on the possible mediators implicated in these potential effects, with dopamine, serotonin, and noradrenaline being the principal neurotransmitters implicated, both through interference with receptors and with their metabolism by monoamino oxidases, as well as through neuro-endocrine and neuroprotective effects. There are approximately 650 reports of antidepressant-like medicinal plants in PubMed; 155 of them have been compiled in this review, with a relevant group yielding positive results. Saffron and turmeric are the most relevant species studied in both preclinical and clinical studies; St. Johnʼs wort or kava have also been tested extensively. To the best of our knowledge, no review to date has provided a comprehensive understanding of the biomolecular mechanisms of action of these herbs or of whether their potential effects could have real benefits. The purpose of this narrative review is to provide an update regarding medicinal plants from the year 2000 to the present to examine the therapeutic potential of these antidepressant-like plants in order to contribute to the development of new therapeutic methods to alleviate the tremendous burden that depression causes worldwide.
... Therefore, to evaluate the antidepressant activity in mice, tail suspension method was performed. Antidepressant drugs increased time (Kwon et al., 2010). In the TST, acute and repeated PNEO treatment decreased immobility time in a dose dependent manner, indicating that PNEO can be a choice of agent, which is used to manage depression. ...
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In this study, the anxiolytic activity of Piper nigrum essential oil (PNEO) was evaluated in the elevated plus maze (EPM) and the antidepressant-like effect was evaluated through tail suspension test (TST) in mice. Flumazenil, a competitive inhibitor of GABAA receptor in the benzodiazepine site and WAY-100635 maleate salt, a 5-HT1A receptor antagonist were used to find out the possible mechanism(s) of action of PNEO. To exclude the false-positive results due to the enhancement of the locomotor activity, the animals were submitted to open field test (OFT). We also measured monoamines levels of the mice brain after acute PNEO treatment. The data obtained from the study suggest that the anxiolytics and antidepressant-like effect of PNEO have observed in EPM and TST respectively in a dose-dependent manner after oral acute and repetitive treatment. WAY-100635, but not flumazenil was able to reverse the effect of PNEO in EPM and TST both, indicating the possible involvement of 5-HT1A receptor. The neurochemical analysis showed no alteration in monoamine levels in mice brains. Furthermore, no locomotor impairment or sign of toxicity or changes in body weight or abnormalities in the biochemical parameters, except for a significant decrease in total cholesterol level was observed after treatment with PNEO. The findings suggest that Piper nigrum EO possesses a dual anxiolytic and antidepressant-like effect through the possible involvement of serotonergic transmission.
... Intraperitoneal administration of AMPT, 100 mg/kg, was done 4 h before giving APG or saline (control) and 60 min later, they were evaluated in TST (Cryan et al., 2002;Can et al., 2013). In other experimental groups, phentolamine (5 mg/kg, i.p.) (Kwon et al., 2010), propranolol (2 mg/kg, i.p.) (Schreiber et al., 2000), SCH 23390 (0.05 mg/kg, s.c.) (Yalcin et al., 2007), and sulpiride (50 mg/kg, i.p.) (Bradford et al., 2010), were given 15 min before administering saline or APG and TST was done 60 min later (Gavello-Baudy et al., 2008). The experiment was also repeated with PCPA (inhibitor of tryptophan hydroxylase) and ondansetron to determine the role of the serotonergic system (5-HT3 receptor antagonist). ...
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Background and Objective Although, the anti-depressant like effects of apigenin (APG) are documented in the literature, the underlying mechanism for exerting such an effect is still not clear. In this research, an attempt was made to determine the possible role of APG for antidepressant activity through serotonergic and catecholaminergic systems using standardized animal models. Materials and Methods The antidepressant property of APG was determine by involving tail suspension (TST) and modified forced swimming tests (MFST). The effect of APG was evaluated at 25 and 50 mg/kg. In mechanistic models, animals were pretreated with catecholaminergic and serotonergic antagonists prior to administration of APG. The results obtained were statistically analyzed to determine the level of significance. Results The period of immobility in both models (TST and MFST) was significantly reduced by APG (25 and 50 mg/kg). The best therapetuic dose of APG (50 mg/kg) was selected for the mechanistic study. The anti-immobility effect of APG declined to a significant extent upon pretreatment with catecholaminergic antagonists (α-methyl-para-tyrosine methyl ester; SCH 23390; sulpiride; phentolamine) and serotonergic inhibitors (p-clorophenylalanine-methyl-ester; ondansetron) in both TST and MFST models. The antidepressant benefits of apigenin were only modestly reversed when rats were given propranolol. Conclusions The findings suggest that APG's antidepressant effect is mediated by the α-adrenergic, dopaminergic and 5-HT3 serotonergic receptors.
... The dose selection of drugs and extract was done in accordance to the previous studies (Ni et al., 2013;Kwon et al., 2010;Binfaré et al., 2009;Rodrigues et al., 2002;Gilhotra et al., 2010). ...
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The aim of this study was to investigate the antidepressant activity of hydroalcoholic extract Agaricus blazei (273 and 819 mg/kg; orally) in stressed and unstressed Swiss albino mice. Mice were immobilized to induce stress. Fluoxetine 20 mg/kg orally was given to stressed and unstressed animals and immobility time was noted by using forced swim test and tail suspension test. The concentration of plasma nitrite was also evaluated in stressed and unstressed mice. The effect of prazosin (α1-adrenoceptor antagonist), p-CPA (parachlorophenylalanine–tryptophan hydroxylase inhibitor) and 7-nitro-indazole (nNOS inhibitor) on the antidepressant activity of A. blazei was also evaluated. A. blazei and fluoxetine significantly decreased the duration of immobility time in stressed and unstressed mice, showing significant antidepressant activity. No substantial change was found in the locomotor activity. However, a significant reduction in the level of plasma nitrite was also noted in stressed mice. Hydroalcoholic extract showed prominent antidepressant activity in mice.
... Several natural products, such as Hypericum perforatum L. (Hypericaceae), Rhodiola rosea L. (Crassulaceae), Vitis vinifera L. (Vitaceae), and Bupleurum falcatum L. (Apiaceae), have been known to be effective in depression (Nathan 2001;Kurkin et al. 2006;Kwon et al. 2010;Xu et al. 2010). Further, polyphenols (such as chlorogenic acid, curcumin, resveratrol, and proanthocyanidins), flavonoids (such as rutin, tannin, and quercetin), and cannabinoids (such as tetrahydrocannabinol, cannabichromene, and cannabidiol) are known to alleviate depression (Noldner and Schotz 2002;Anjaneyulu et al. 2003;Kulkarni et al. 2008;El-Alfy et al. 2010;Xu et al. 2010;Pathak et al. 2013;Chandrasekhar et al. 2017;Zhu et al. 2019). ...
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Context: Depression is a severe mental illness caused by a deficiency of dopamine and serotonin. Cannabis sativa L. (Cannabaceae) has long been used to treat pain, nausea, and depression. Objective: This study investigates the anti-depressant effects of C. sativa (hemp) seed ethanol extract (HE) in chlorpromazine (CPZ)-induced Drosophila melanogaster depression model. Materials and methods: The normal group was untreated, and the control group was treated with CPZ (0.1% of media) for 7 days. The experimental groups were treated with a single HE treatment (0.5, 1.0, and 1.5% of media) and a mixture of 0.1% CPZ and HE for 7 days. The locomotor activity, behavioural patterns, depression-related gene expression, and neurotransmitters level of flies were investigated. Results: The behavioural patterns of individual flies were significantly reduced with 0.1% CPZ treatment. In contrast, combination treatment of 1.5% HE and 0.1% CPZ significantly increased subjective daytime activity (p < 0.001) and behavioural factors (p < 0.001). These results correlate with increased transcript levels of dopamine (p < 0.001) and serotonin (p < 0.05) receptors and concentration of dopamine (p < 0.05), levodopa (p < 0.001), 5-HTP (p < 0.05), and serotonin (p < 0.001) compared to those in the control group. Discussion and conclusions: Collectively, HE administration alleviates depression-like symptoms by modulating the circadian rhythm-related behaviours, transcript levels of neurotransmitter receptors, and neurotransmitter levels in the CPZ-induced Drosophila model. However, additional research is needed to investigate the role of HE administration in behavioural patterns, reduction of the neurotransmitter, and signalling pathways of depression in a vertebrate model system.
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The history of herbal medicines is as old as human civilization. The documents revealed that plants were used medicinally in China, India, Egypt and Greece long before the beginning of the Christian era. The human being appears to be afflicted with more diseases than any other animal's species. They sought to alleviate their sufferings from injury and disease by taking advantage of plant growing around them. Depression is such a common mental disorder, which affects the personal and social relations of a person. There are variety of neuro chemical theories proposed and number of synthetic antidepressant drugs are available now a days, however their effectiveness does not come up the entire range of population suffering from this disorder. Moreover the side effects and the drug interactions are major restrictions in their clinical applications. Unlike, synthetic medications, herbal medicines are widely used across the globe due to their wide applicability and therapeutic efficacy associated with least side effects, which in turn has initiated the scientific research regarding the antidepressant activity. The aim of this review is to enlist those plants which have antidepressant activity and the various experimental models used to screen their antidepressant activity.
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Objectives: Herbs are frequently and concurrently used with prescribed drugs by patients worldwide. While clinical trials have found some herbs to be as useful as standard psychiatric drugs, most clinicians are unaware of their pharmacological mechanisms. Methods: We searched English language and other language literature with English abstracts listed in PubMed website, supplemented by additional through Google Scholar’s free academic paper abstract website for publications on herbs, focusing on their clinical usages in mental disorders, their neurobiology and pharmacology. Results: A major reason for herbs remaining outside of mainstream psychiatry is that the terminology and concepts in herbal medicine are not familiar to psychiatrists in general. Many publications regarding the use of herbal medicine for psychiatric disorders are deficient in details regarding diagnosis, criteria for response and the neurobiology details as compared to publications on standard psychotropic drugs. Nomenclature for herbal medicine is usually confusing and is not conducive to an easy understanding of their mode of action in psychiatric disorders. Conclusion: The recent Neuroscience based Nomenclature (NbN) for psychotropics methodology would be a logical application to herbal medicine in facilitating a better understanding of the use of herbal medicine in psychiatry.
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Ethnopharmacological relevance: Suanzaorenhehuan Formula (SHF) has been used for treating depression-like disorders for many years in China. The saponins part of the SHF (SSHF) extract was the antidepressant effective component. Aim of study: To investigate the antidepressant-like effect of SSHF and its possible mechanisms. Materials and methods: Experimental approaches including the forced swim test (FST), the tail suspension test (TST) and unpredictable chronic mild stress (UCMS) were used to evaluate the effects of SSHF. The possible mechanisms were explored by measuring monoamine neurotransmitter in mice frontal cortex and hippocampus, testing monoamine oxidase enzyme (MAO) activities, antioxidant enzyme activities and free radicals levels in the brains of UCMS-exposed mice. Results: The results showed that SSHF (10, 20, 40mg/kg) significantly decreased the immobility period in FST and TST in mice after two-week treatment. Whereas, SSHF had no significant effect on locomotor activity in mice. It was also found that the serotonin (5-HT) and noradrenaline (NE) levels in the hippocampus and frontal cortex were significantly increased only in 40mg/kg SSHF treated mice. In addition, SSHF (10, 20, 40mg/kg) significantly inhibited monoamine oxidase-A (MAO-A) and monoamine oxidase-B (MAO-B) after 21-day UCMS exposure. SSHF (10, 20, 40mg/kg) significantly decreased the nitrous oxide (NO) levels, and increased the activities of total antioxidant capability (T-AOC), glutathione peroxidase (GSH-PX), and catalase (CAT) in different degrees in the brains of UCMS-exposed mice. Conclusions: Our results suggested that SSHF may effectively produce an antidepressant-like effect, which appeared to involve the serotonergic, noradrenergic, monoamine oxidase enzyme and antioxidant systems.
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Depression is a heterogeneous group of brain disorders characterized by a wide range of symptoms that result in psychomotor and cognitive impairments. Depression is accompanied with loss of pleasure or interest, feeling of guilt, decreased energy and low self worth. Depression is also a major cause of morbidity worldwide, estimated to affect 350 million people. It is highly prevalent, accounting for more disability than any other disorder and its prognosis and management are also poor due to the little understanding of the disorder. Many categories of synthetic and natural compounds have been reported to possess neuropsychiatric activity. Various adverse effects are associated with synthetic drugs which are used in the treatment of depression. Loss of libido, tolerance, physical dependence and insomnia is associated with selective serotonin (5 HT) reuptake inhibitors and tricyclic antidepressants; several drug­drug interactions may occur. The aim of this review is to enlist those plants which have antidepressant activity.
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p class="Abstract">Depression is a life-threatening, debilitating, and common disease affecting different segments of community. Chemical and synthetic drugs available to treat this disease cause many adverse effects and may lead to complete recovery in only 50% of patients. At the same time, medicinal plants have been reported to exert optimal pharmacological effects in treating depression in different models. In this review, the relevant articles indexed in the reliable databases PubMed, PubMed central, Scopus and Web of Science were review-ed. The review indicated that most medicinal plants exerted antidepressant effects through synaptic regulation of serotonin, noradrenaline, and dopamine, regulating activity of hypothalamic-pituitary-adrenal axis, reinfor-cing anti-oxidant defense system, and decreasing inflammatory mediators. The medicinal plants and their active compounds can relieve depression through different pathways and hence are considered a new source to produce antidepressants.</p
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The increasing cases of depression has made the searches for new drugs and understanding of the underligning neurobiology of this psychiatric disorder a necessity. Here, we modified the structure of salvinorin A (a known halucinogen) and investigated antidepressant-like activity of its four derivatives; 22-methylsulfanylsalvinorin A(SA1), 2-O-cinnamoylsalvinorin B (CSB), 22-azidosalvinorin A (SA2), and 2-O-(4’-azidophenylsulfonyl)salvinorin B (SA3). Prior to behavioural tests (Irwin test, open field test – OFT, forced swimming test – FST and tail suspension test – TST), SA1 was prepared by reacting salvinorin B and methylthioacetic acid with 89% yield; CSB was obtained from the reaction of salvinorin B and cinnamic acid with 92% yield; SA2 was obtained from the reaction of salvinorin B and azidoacetic acid with 81% yield; and SA3 was prepared by reacting salvinorin B with 4-azidophenylsulfonyl chloride with 80% yield. Oral treatment of mice with these derivatives (1–1000 mg/kg) did not elicit toxic sign or death. Unlike SA, SA1, CSB and SA3, treatment with SA2 (5, 10 and 20 mg/kg) decreased the immobility (TST and FST) and swimming time (FST) without altering locomotor activity in OFT. A decrease in the immobility time in TST and FST confirmed antidepressant-like property of SA2. Although p-chlorophenylalanine (serotonin depletor) or WAY100635 (selective 5-HT1A receptor antagonist) did not attenuate effect of SA2, alpha-methyl-para-tyrosine (catecholamine depletor) and prazosin (selective α1-receptor antagonist) attenuated this effect. SA2 mildly inhibited monoamine oxidase and showed affinity for α1A, α1B, α1D and κ-opioid receptor subtypes. In summary, SA2 induced monoamine-mediated antidepressant-like effect.
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Alpha (α)-asarone is one of the main psychoactive compounds, present in Acorus species. Evidence suggests that the α-asarone possess an antidepressant-like activity in mice. However, the exact dose-dependent effect of α-asarone and mechanism(s) involved in the antidepressant-like activity are not clear. The present study aimed to investigate the dose-dependent effect of α-asarone and the underlining mechanism(s) involved in the antidepressant-like activity of α-asarone in the mouse model of tail suspension test (TST). In this study, the acute effect of α-asarone per se at different doses (10-100 mg/kg, i.p.) on immobility in the TST was studied. Additionally, the possible mechanism(s) involved in the antidepressant-like effect of α-asarone was studied using its interaction with noradrenergic and serotonergic neuromodulators in the TST. The present results reveal that the acute treatment of α-asarone elicited biphasic responses on immobility such that the duration of the immobility time is significantly reduced at lower doses (15 and 20 mg/kg, i.p.) but increased at higher doses (50 and 100 mg/kg, i.p.) in the TST. Besides, α-asarone at higher doses (50 and 100 mg/kg, i.p.) significantly decreased the spontaneous locomotor activity. Moreover, pretreatment of mice with noradrenergic neuromodulators such as AMPT (100 mg/kg, i.p., a catecholamine synthesis inhibitor), prazosin (1 mg/kg, i.p., an α1-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an α2-adrenoceptor antagonist) and with serotonergic neuromodulators such as PCPA (100 mg/kg, i.p., once daily for four consecutive days, a serotonin synthesis inhibitor,) and WAY100635 (0.1 mg/kg, s.c., a selective 5-HT1A receptor antagonist) significantly reversed the anti-immobility effect of α-asarone (20 mg/kg, i.p.). Taken together, our results suggest that the acute treatment with α-asarone elicited biphasic actions in the TST in which antidepressant-like effect was seen at relatively lower doses (15 and 20 mg/kg, i.p.) and depressive-like activity at relatively higher doses (50 and 100 mg/kg, i.p.). Furthermore, it has been revealed that the antidepressant-like effect of α-asarone could be mediated through both noradrenergic (α1 and α2 adrenoceptors) and serotonergic (particularly, 5-HT1A receptors) systems.
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Alpha (α)-asarone is one of the main psychoactive compounds, present in Acorus species. Evidence suggests that the α-asarone possess an antidepressant-like activity in mice. However, the exact dose-dependent effect of α-asarone and mechanism(s) involved in the antidepressant-like activity are not clear. The present study aimed to investigate the dose-dependent effect of α-asarone and the underlining mechanism(s) involved in the antidepressant-like activity of α-asarone in the mouse model of tail suspension test (TST). In this study, the acute effect of α-asarone per se at different doses (10–100 mg/kg, i.p.) on immobility in the TST was studied. Additionally, the possible mechanism(s) involved in the antidepressant-like effect of α-asarone was studied using its interaction with noradrenergic and serotonergic neuromodulators in the TST. The present results reveal that the acute treatment of α-asarone elicited biphasic responses on immobility such that the duration of the immobility time is significantly reduced at lower doses (15 and 20 mg/kg, i.p.) but increased at higher doses (50 and 100 mg/kg, i.p.) in the TST. Besides, α-asarone at higher doses (50 and 100 mg/kg, i.p.) significantly decreased the spontaneous locomotor activity. Moreover, pretreatment of mice with noradrenergic neuromodulators such as AMPT (100 mg/kg, i.p., a catecholamine synthesis inhibitor), prazosin (1 mg/kg, i.p., an α1-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an α2-adrenoceptor antagonist) and with serotonergic neuromodulators such as PCPA (100 mg/kg, i.p., once daily for four consecutive days, a serotonin synthesis inhibitor,) and WAY100635 (0.1 mg/kg, s.c., a selective 5-HT1A receptor antagonist) significantly reversed the anti-immobility effect of α-asarone (20 mg/kg, i.p.). Taken together, our results suggest that the acute treatment with α-asarone elicited biphasic actions in the TST in which antidepressant-like effect was seen at relatively lower doses (15 and 20 mg/kg, i.p.) and depressive-like activity at relatively higher doses (50 and 100 mg/kg, i.p.). Furthermore, it has been revealed that the antidepressant-like effect of α-asarone could be mediated through both noradrenergic (α1 and α2 adrenoceptors) and serotonergic (particularly, 5-HT1A receptors) systems.
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Major depression is a debilitating disorder, predicted to be the second most prevalent human malady by the year 2020. Although a variety of chemical antidepressant remedies like tricyclic antidepressants, monoamine oxidase inhibitors and selective serotonin reuptake inhibitors are available, yet approximately 30% of depressed patients are resistant to the existing drugs and remaining 70% do not achieve full remission. Therefore, a constant urge continues for discovery of newer, better-tolerated and more efficacious treatments of depression, which include search for discovery of medicinal plants with potential antidepressant activity. The present paper discusses anti-depression potential of 70 medicinal plants with emphasis on their pre-clinical and clinical reports. Majority of plants shows antidepressant activity through serotonergic, noradrenergic and dopaminergic systems.
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There is enough data available now to believe that nature has provided cure of almost every ailment through herbal medicine or management. Therefore, now there is lot of emphasis on identification, evaluation, development and characterization of numerous plants and their active constituents against several diseases including depression. Depression is not only one of the most common ailments but also a highly complex condition to study. Even though several antidepressant drugs are available now, yet their effectiveness and usefulness are highly questionable especially because of their side effects. As herbal remedies are generally associated with favourable safety profiles therefore they have the possible potential to deliver effective replacements to currently available synthetic antidepressants. More recently, efforts have been focused on characterization of pharmacologically active ingredients and to identify the mode of action of herbal antidepressant medicines. This review describes a brief introduction of different animal models for depression and discusses the advantages and disadvantages for each approach. Then we have summarized possible plant phytochemicals as antidepressant drug and the underlying mechanisms. In the main body of the review, we have discussed in detail the most frequently used plants (21) being investigated for the treatment of depression. Additionally, we have provided the list of medicinal plants (92) representing their origin, parts used, extraction method, evaluation method and possible active ingredient. In the final part of the review we have presented the summary of clinical trials on the use of medical plants for depression and their active constituents.
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Background and Objective:Bupleurum falcatum (BF) extract, a natural product with anti-inflammatory properties, has been traditionally used to treat menopausal symptoms, but its role in osteoporosis, another serious health concern of menopausal women, remains unknown. Here we investigated whether and how BF prevents estrogen deficiency-induced bone loss using both in vitro and in vivo models. Methods: Female Sprague-Dawley rats were ovariectomized (OVX) and subjected to oral BF treatment daily for 8 weeks. Additionally, pre-osteoclastic RAW 264.7 cells were employed to evaluate the effects of BF and its underlying mechanism on receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast formation in vitro. Results: A high dose of BF partially prevented ovariectomy (OVX)-induced bone loss and reduced the levels of tartrate-resistant acid phosphatase (TRAP) in serum and osteoclast numbers in femurs of OVX rats. Furthermore, BF clearly inhibited RANKL-induced osteoclast differentiation and bone resorption activity in RAW 264.7 cells. BF also inhibited the osteoclastogenic transcription factors c-Fos and nuclear factor of activated T cells c1 (NFATc1) and, consequently, downregulated the expression of osteoclast marker genes. Moreover, BF upregulated interferon-β (IFN-β)/inducible nitric oxide synthase (iNOS)/nitric oxide (NO) signaling, even though it had no impact on mitogen-activated protein kinases (MAPK) or NF-κB. The inhibition of osteoclast formation by BF was abrogated by iNOS-specific inhibitors. Consistent with cellular studies, BF upregulated iNOS protein expression in femurs from OVX rats. Conclusion: Taken together, our results indicate that BF partially prevented estrogen deficiency-induced bone loss with anti-osteoclastogenic activity potentially due to enhanced iNOS/NO signaling.
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Xiaoyao powder (XYP) is a valuable traditional Chinese Medicine (TCM) prescription developed for depression. Previous findings have suggested that the low polar extract of XYP (XYP-A) was more effect than other parts and its main ingredients included ligustilide, (2Z,8Z,10E)-pentadecatriene-4,6-diyn-1-ol (RB-1), (2Z,8E,10E)-pentadecatriene-4,6-diyn-1-ol (RB-2), (2Z,8Z,10E)-heptadecatriene-4,6-diyn-1-ol (RB-3), and bupleurynol (RB-4). However, the correlation between concentration of main ingredients and effects is still indeterminate. This study developed an ultra performance lipid chromatography combined with photo-diode array detector (UPLC-PDA) method to determine the contents of main ingredients in serum and tissues for pharmacokinetics and tissue distribution analysis. And, norepinephrine (NE) and 5-hydroxytryptamine (5-HT) were selected as the pharmacodynamic index and determined using the method of high performance lipid chromatography combined with fluorescence detector (HPLC-FD) in the serum for pharmacodynamics analysis. The DAS3.0 software was used to fit the pharmacokinetics-pharmacodynamics (PK-PD) model. The pharmacokinetic assay revealed that the absorption of polyacetylene compound was more favorable under pathological status. And, the result of tissue distribution showed that RB-2 and RB-4 were rapidly and widely distributed in tissues, and easy to cross the blood-brain barrier. The comparison of the value of NE and 5-HT in chronic unpredictable mild stress (CUMS) and control group rats suggested that 5-HT might be the main targets for the four polyacetylene compounds. The present study demonstrated that XYP-A showed the certain therapeutic effect of for depression safely and that polyacetylene compounds might be active ingredient for depression.
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We have recently demonstrated that the hydroethanolic extracts of Impatiens glandulifera Royle (Balsaminaceae) have antianxiety effect in mice. The present study was aimed to investigate an antidepressant activity of hyperoside (HYP) and protocatechuic acid (PCA), two polyphenols isolated from the aerial parts of this plant, using the forced swimming test (FST) and tail suspension test (TST) in mice. The implication of the monoaminergic system in this effect was assessed and brain-derived neurotrophic factor (BDNF) expression was measured. At doses 1.875, 3.75 and 7.5 mg/kg, HYP and PCA significantly reduced immobility in the FST and TST, without affecting locomotor activity of mice. Pretreatment with p-chlorophenylalanine (PCPA 100 mg/kg, a serotonin synthesis inhibitor) or α-methyl-DL-tyrosine (AMPT 100 mg/kg, a catecholamine synthesis inhibitor) was able to prevent antidepressant-like effect of HYP and PCA (3.75 mg/kg). Sub-effective doses of fluoxetine (5 mg/kg) or reboxetine (2 mg/kg) were capable of potentiating the effect of a sub-effective dose of HYP (0.94 mg/kg) in the FST. Co-administration of sub-effective dose of PCA (0.94 mg/kg) and reboxetine (2 mg/kg) resulted in reducing immobility in the FST. The antidepressant-like effect of HYP and PCA was also prevented by the administration of sulpiride (50 mg/kg), a D2 antagonist. In addition, HYP (3.75 and 7.5 mg/kg) and PCA (7.5 mg/kg) improved the expression of hippocampal BDNF of mice subjected to TST. Altogether, our findings suggest that HYP and PCA exert antidepressant-like effects in mice, which was possibly mediated by monoaminergic system and the upregulation of BDNF level.
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Background Considering the pharmacological potential of solidagenone from Solidago chilensis, the present investigation was carried out to evaluate its antidepressant-like effect in mice with bacterial lipopolysaccharide (LPS)-induced depressive like behavior and its mode of action through the measurement of neuroinflammatory and oxidative markers. Materials and methods In the prophylactic test, the mice were pretreated with solidagenone (1, 10 or 100 mg/kg, p.o) and after one hour received LPS. In therapeutic test, the mice received LPS and after 5 h were treated with solidagenone (1, 10 or 100 mg/kg, p.o). In both experimental approaches, the animals were submitted to OFT and to the TST after 6 and 24 h of the LPS administration, respectively. One hour after the TST the animals were euthanized, the blood was collected, the cortex was removed and biochemical analyzes were performed for measurement of the inflammatory and oxidative stress markers. Results The LPS induced sickness- and depressive-like behaviors and increased the cortical activity of myeloperoxidase (MPO), as well as the IL-6 and TNF amount. Interestingly, the pretreatment with solidagenone at 100 mg/kg avoided the behavioral alterations in OFT. In the mice post treated with solidagenone, all tested doses of resulted in an antidepressant-like effect evidenced by the decrease in immobility time in the TST. This effect was accompanied by a decrease in the MPO activity and in the IL-6 and TNF levels in the cortex in parallel to the increase in catalase activity. Conclusions The solidagenone has a promissor antidepressant-like potential, which can result of its beneficial action in the neuroinflammation process and due its antioxidant capability at the central nervous system.
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Aegle marmelos Corr. (Rutaceae) is reported to have a wide range of biological activities and the leaves of this plant are used as a brain tonic traditionally in India. In this study, the psychoneuropharmacological activities of essential oil obtained from the leaves of Aegle marmelos were investigated for the first time and the possible mechanistic pathway involved in these activities was also investigated, along with molecular docking study. The chemical composition of extracted essential oil Aegle marmelos (AMEO) was analyzed by Gas chromatography combined with Mass-spectrometer (GC/MS). D-limonene (46.08 %) and α-phellandrene (35.90 %) were characterized as the major constituents. Firstly, the selection of the dose of essential oil was made by calculating the intraperitoneal LD50 value. Then AMEO (25-100 mg/kg, i.p) was investigated for general behavioral, antianxiety, sedative, anti convulsion, antidepressant, and motor coordination activities. The essential oil exhibited significant anxiolytic and antidepressant-like activities at all doses. Whereas, noticeable sedative and anticonvulsant effects were achieved at a high dose of essential oil. In addition, to find out the possible connections of the GABAergic and serotonergic system in these activities, test and positive control groups were pretreated with flumazenil and p-chloro-phenylalanine. The findings of in vivo study indicated that essential oil (EO) activity seems to have occurred via GABAergic and serotonergic pathways. A molecular docking (in silico) study also was accomplished to establish the possible mechanistic pathway involved in in vivo activity and the findings of the in silico study might validate the results of in vivo activity.
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Background Aegle marmelos Corr. (Rutaceae) commonly known as ‘Indian Bael’ has been used as a brain tonic traditionally. However, despite this traditional use, not enough scientific report is present that can confirm the use of this plant in neurological disorders. Thus, the total sterols fraction and stigmasterol from the leaves of Aegle marmelos were investigated for antidepressant-like effect along with their possible mechanism(s) of action by primarily performing acute toxicity study of total sterols. Methods An acute toxicological study was carried out at a single oral dose of 2000 mg/kg. Sign of toxicity was observed by estimating biochemical and performing histopathological analysis. For the antidepressant-like effect, different doses of total sterols (50-200 mg/kg, p.o. for seven days) and stigmasterol (5- 20 mg/kg, i.p. acute) were administered in mice using TST and FST models. To evaluate the mechanism of action, mice were pretreated with GABA, 5-HT, DA, adrenergic antagonists, and glutamate agonists. Furthermore, a neurochemical study was performed following TST and molecular docking study was also performed to determine the binding affinity of stigmasterol. Results Total sterols fraction presents no sign of toxicity up to the oral dose of 2000 mg/kg. Oral treatment of total sterols and acute intraperitoneal treatment of stigmasterol (except 5 mg/kg) reduced the immobility time significantly. Pretreatment with pCPA (5-HT synthesis inhibitor) and NMDA (an agonist of the glutamate site) effectively reversed the immobility time of total sterols and stigmasterol (except pCPA) in TST. However, bicuculline (competitive GABA antagonist), haloperidol (D2 dopaminergic antagonist) and prazosin (α1 adrenergic antagonist) could not reverse the immobility time. Meanwhile, total sterols also effectively altered the hippocampus 5-HT and Glu levels. Also, the result of the molecular docking study depicted that stigmasterol has an affinity to the NMDA receptor. Conclusions The present study suggests that the total sterols fraction did not produce any acute toxicity in rats. Also, we reported that total sterols, stigmasterol and sub-effective stigmasterol co-administration with fluoxetine significantly reduced the time of immobility in TST and FST confirmed the antidepressant-like effect of total sterols fraction and stigmasterol. Moreover, further findings suggest that the antidepressant-like effect of total sterols might be mediated by the serotonergic and glutamatergic systems. Whereas only the glutamatergic system was involved in the antidepressant activity of stigmasterol.
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Experimental appraisal of antidepressants (ADs) in varied animal models is the need of time. There is a regular hunt for novel models with ease and quick screening of AD activity. As previous studies depict AD effect ofondansetron (OND) in animal models, the study was carried out to compare the efficacy of two behavioral despair models in delineating antidepressant-like effect of OND. OND in tail suspension test (TST) produced significant AD effect at a low dose of 0.25 mg/kg, as depicted by reduction in immobility period of drug-treated mice compared to control group (p<0.05), whereas OND in forced swim test (FST) produced insignificant AD effect at the doseof 0.25 mg/kg as compared to control (p>0.05). Results of our study highlight AD-like activity of OND in TST and FST models of depression, but TST in mice seems to be more sensitive in evaluating the AD like effect of OND.
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This study presents data on the use of complementary and alternative therapies to treat anxiety and depression in the United States. The data came from a nationally representative survey of 2,055 respondents (1997-1998) that obtained information on the use of 24 complementary and alternative therapies for the treatment of specific chronic conditions. A total of 9.4% of the respondents reported suffering from "anxiety attacks" in the past 12 months; 7.2% reported "severe depression." A total of 56.7% of those with anxiety attacks and 53.6% of those with severe depression reported using complementary and alternative therapies to treat these conditions during the past 12 months. Only 20.0% of those with anxiety attacks and 19.3% of those with severe depression visited a complementary or alternative therapist. A total of 65.9% of the respondents seen by a conventional provider for anxiety attacks and 66.7% of those seen by a conventional provider for severe depression also used complementary and alternative therapies to treat these conditions. The perceived helpfulness of these therapies in treating anxiety and depression was similar to that of conventional therapies. Complementary and alternative therapies are used more than conventional therapies by people with self-defined anxiety attacks and severe depression. Most patients visiting conventional mental health providers for these problems also use complementary and alternative therapies. Use of these therapies will likely increase as insurance coverage expands. Asking patients about their use could prevent adverse effects and maximize the usefulness of therapies subsequently proven to be effective.
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The development of serotonin receptor knockout mice has provided an opportunity to study antidepressant drug effects in animals with targeted genetic deletion of receptors involved in antidepressant responses. In the current study, the effects of two types of antidepressant drugs, the selective serotonin reuptake inhibitors fluoxetine and paroxetine and the selective norepinephrine reuptake inhibitor desipramine, were examined in 5-hydroxytryptamine (5-HT)(1A) and 5-HT(1B) receptor mutant mice using the tail suspension test (TST). Under baseline conditions, the immobility of 5-HT(1A) receptor mutant mice, but not 5-HT(1B) receptor mutant mice, was significantly lower than that of wild-type mice. The decreased baseline immobility in 5-HT(1A) receptor mutant mice was reversed by pretreatment with alpha-methyl-para-tyrosine, but not by para-chlorophenylalanine, suggesting mediation by enhanced catecholamine function. In wild-type mice, fluoxetine (10.0--20.0 mg/kg i.p.) and desipramine (5.0--20.0 mg/kg i.p.) both significantly decreased immobility in the TST. In 5-HT(1A) receptor mutant mice, desipramine (20.0 mg/kg i.p.) significantly decreased immobility, whereas fluoxetine (20.0 mg/kg i.p.) and paroxetine (20.0 mg/kg i.p.) had no effect. The immobility of 5-HT(1B) receptor mutant mice was decreased similarly by desipramine (5.0--20.0 mg/kg i.p.). However, the effect of low doses of fluoxetine were significantly augmented in the 5-HT(1B) receptor mutant mice (2.5--20.0 mg/kg i.p.) compared with wild-type mice. Administration of selective 5-HT receptor antagonists in wild-type mice partially reproduced the phenotypes of the mutant mice. These results suggest that 5-HT(1A) and 5-HT(1B) receptors have different roles in the modulation of the response to antidepressant drugs in the TST.
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At an estimated cost of almost $50 billion a year, the socioeconomic burden of major depressive disorder is enormous. Although remission has been identified as the key goal of treatment, such treatment must be highly acceptable to patients, predictably effective, and carry minimal adverse effects. The cornerstone of depression management, remission can improve clinical status, functional ability, and quality of life for the patient while lowering utilization costs related to the disease and its comorbidities. Initially, the goals of therapy are to: (1) reduce and ultimately remove all signs and symptoms of the depressive syndrome; (2) restore occupational and psychosocial function to the asymptomatic state; and (3) achieve and maintain remission. Most patients can achieve these goals with the help of antidepressant medications, problem-focused psychotherapy, or a combination of the 2 methods. Following an initial assessment of the patient, treatment of depression has 3 phases: acute, continuation, and maintenance. Although adherence to treatment is crucial to successful treatment of depression, only about 25% to 35% of patients will achieve remission after 6 to 8 weeks of treatment; another 15% to 20% may remain depressed for months or years. Patients who achieve remission are much less likely to relapse than those who do not. Much debate has focused on the relative merits of prescribing selective serotonin reuptake inhibitors or venlafaxine. Results of a pooled analysis of 8 such comparative studies are presented.
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Current treatments for depression are inadequate for many individuals, and progress in understanding the neurobiology of depression is slow. Several promising hypotheses of depression and antidepressant action have been formulated recently. These hypotheses are based largely on dysregulation of the hypothalamic-pituitary-adrenal axis and hippocampus and implicate corticotropin-releasing factor, glucocorticoids, brain-derived neurotrophic factor, and CREB. Recent work has looked beyond hippocampus to other brain areas that are also likely involved. For example, nucleus accumbens, amygdala, and certain hypothalamic nuclei are critical in regulating motivation, eating, sleeping, energy level, circadian rhythm, and responses to rewarding and aversive stimuli, which are all abnormal in depressed patients. A neurobiologic understanding of depression also requires identification of the genes that make individuals vulnerable or resistant to the syndrome. These advances will fundamentally improve the treatment and prevention of depression.
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Mice unable to synthesize norepinephrine (NE) and epinephrine due to targeted disruption of the dopamine beta-hydroxylase gene, Dbh, were used to critically test roles for NE in mediating acute behavioral changes elicited by different classes of antidepressants. To this end, we used the tail suspension test, one of the most widely used paradigms for assessing antidepressant activity and depression-related behaviors in normal and genetically modified mice. Dbh(-/-) mice failed to respond to the behavioral effects of various antidepressants, including the NE reuptake inhibitors desipramine and reboxetine, the monoamine oxidase inhibitor pargyline, and the atypical antidepressant bupropion, even though they did not differ in baseline immobility from Dbh(+/-) mice, which have normal levels of NE. Surprisingly, the effects of the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, sertraline, and paroxetine were also absent or severely attenuated in the Dbh(-/-) mice. In contrast, citalopram (the most selective SSRI) was equally effective at reducing immobility in mice with and without NE. Restoration of NE by using L-threo-3,4-dihydroxyphenylserine reinstated the behavioral effects of both desipramine and paroxetine in Dbh(-/-) mice, thus demonstrating that the reduced sensitivity to antidepressants is related to NE function, as opposed to developmental abnormalities resulting from chronic NE deficiency. Microdialysis studies demonstrated that the ability of fluoxetine to increase hippocampal serotonin was blocked in Dbh(-/-) mice, whereas citalopram's effect was only partially attenuated. These data show that NE plays an important role in mediating acute behavioral and neurochemical actions of many antidepressants, including most SSRIs.
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Nelumbinis Semen is a well-known traditional herbal medicine frequently used in treatment of depression in many Asian countries. In this study, its anti-depression effects in rats were investigated by comparing the test results of those treated with Nelumbinis Semen to those treated with other herbal anti-depressants, including Rehmanniae Radix Preparat, Corni Fructus, Lycii Fructus, Pinelliae Rhizoma and Hypericum Perforatum. In order to induce depression-like symptoms, the animals were placed under chronic mild stress in the form of overnight illumination for 2 consecutive days. They were treated with the respective herbal extract and forced swimming tests were conducted afterwards. The anti-depression effects of each extract were then evaluated based on a measured index, which consisted of struggling time, first latency and first rest duration. These test results show that Nelumbinis Semen provides greater anti-depression effects than the other herbal extracts. Specifically, only the rats treated with Nelumbinis Semen showed significant increases in struggling time (43.9%, p <0.005, p =0.0037) and in first latency time (90.2%, p <0.05, p =0.0116). However, the first rest duration for Nelumbinis Semen treated rats was not significantly different from the other rats. It appears that Nelumbinis Semen provides even greater anti-depression effects than Hypericum Perforatum (commonly referred to as St. John's Wort, perhaps the most widely used natural anti-depressant today). The anti-depression effects of Nelumbinis Semen might be due to the modulation of the amount of neurotransmitters involved in depression.
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Few studies have investigated whether the behavioral effects elicited by different types of antidepressant drugs are mediated by either serotonin (5-HT) or the catecholamines norepinephrine (NE) and dopamine (DA). By depleting 5-HT, or NE and DA, the present study investigated the contributions of these monoamines to the acute behavioral effects of selective serotonin reuptake inhibitors (SSRIs; fluoxetine and citalopram) and norepinephrine reuptake inhibitors (NRIs; desipramine and reboxetine) in the mouse tail suspension test (TST). Depletion of 5-HT tissue content by para-chlorophenylalanine (PCPA), an inhibitor of tryptophan hydroxylase, completely blocked reductions of immobility by the SSRIs in the TST. In contrast, PCPA did not alter the behavioral effects of the NRIs. Inhibition of catecholamine synthesis by alpha-methyl-para-tyrosine (AMPT) reduced brain NE and DA tissue content, whereas disruption of vesicular storage with reserpine decreased brain NE, DA and 5-HT tissue content. However, neither treatment completely prevented responses to desipramine, fluoxetine, or citalopram in the TST. Depleting both newly synthesized and vesicular components of NE and DA transmission with a combination of reserpine and AMPT completely prevented the behavioral effects of desipramine, reboxetine, and fluoxetine and attenuated those of citalopram. Although PCPA did not alter baseline immobility, AMPT and reserpine increased baseline values in the TST. These studies demonstrated that endogenous 5-HT synthesis mediates the behavioral effects of SSRIs, but not NRIs, in the TST. In contrast, disruption of the behavioral effects of NRI and SSRI antidepressants required disruption of both catecholamine synthesis and vesicular storage and release mechanisms.
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At an estimated cost of almost $50 billion a year, the socioeconomic burden of major depressive disorder is enormous. Although remission has been identified as the key goal of treatment, such treatment must be highly acceptable to patients, predictably effective, and carry minimal adverse effects. The cornerstone of depression management, remission can improve clinical status, functional ability, and quality of life for the patient while lowering utilization costs related to the disease and its comorbidities. Initially, the goals of therapy are to: (1) reduce and ultimately remove all signs and symptoms of the depressive syndrome; (2) restore occupational and psychosocial function to the asymptomatic state; and (3) achieve and maintain remission. Most patients can achieve these goals with the help of antidepressant medications, problem-focused psychotherapy, or a combination of the 2 methods. Following an initial assessment of the patient, treatment of depression has 3 phases: acute, continuation, and maintenance. Although adherence to treatment is crucial to successful treatment of depression, only about 25% to 35% of patients will achieve remission after 6 to 8 weeks of treatment; another 15% to 20% may remain depressed for months or years. Patients who achieve remission are much less likely to relapse than those who do not. Much debate has focused on the relative merits of prescribing selective serotonin reuptake inhibitors or venlafaxine. Results of a pooled analysis of 8 such comparative studies are presented.
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The new generic name Martynovocossus nom. nov. (Hemiptera, Palaeontinidae) is proposed as a replacement name for the preoccupied and junior homonym Pseudocossus Martynov, 1931, non Pseudocossus Kenrick, 1914, non Pseudocossus Gaede, 1933. The new genus group is redefined based on new, exceptionally preserved material including complete forewings and hindwings with colour pattern preservation. The synonymies for Martynovocossus zemcuznicovi comb. nov., M. turgaiensis comb. nov., M. strenus comb. nov., M. punctulosus comb. nov., M. bellus comb. nov. and M. ancylivenius comb. nov. are established, and the diagnostic characters for M. strenus comb. nov., M. bellus comb. nov. and M. punctulosus comb. nov. are revised. Two new species, M. decorus sp. nov. and M. cheni sp. nov., are described from the Middle Jurassic Daohugou Lagerstätte. Martynovocossus species display considerable intraspecific variation, particularly in aspects of wing size, venation and colour pattern. A key to species of Martynovocossus is presented. Copyright © 2007 John Wiley & Sons, Ltd.
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This study demonstrated that distinct patterns of active behaviors are produced by antidepressants that selectively inhibit norepinephrine (NE) or serotonin (5-HT) uptake in the rat forced swimming test (FST). A behavior sampling technique was developed to score the active behaviors swimming, climbing and diving, as well as immobility. The rat's behavior was recorded at the end of each 5-s period during the test session. The sampling technique was both reliable, as demonstrated by test-retest reliability and inter-rater reliability, and valid, as shown by comparison to the timing of behavior durations. Five different antidepressant drugs which block monoamine uptake and two 5-HT1A receptor agonists were shown to decrease immobility in the FST; however, they produced distinct patterns of active behaviors. The selective NE uptake inhibitors desipramine and maprotiline selectively increased climbing, whereas the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, sertraline and paroxetine selectively increased swimming. The 5-HT1A receptor agonists 8-OH-DPAT and gepirone also selectively increased swimming. These results show that:1) SSRIs are not false negatives in the FST; 2) at least two behaviorally distinct processes occur in the FST; and 3) enhancement of NE neurotransmission may mediate climbing in the FST, whereas enhancement of 5-HT neurotransmission may mediate swimming.
Article
Depression in the elderly is nowadays a predominant health care problem, mainly due to the progressive aging of the population. It results from psychosocial stress, polypathology, as well as some biochemical changes which occur in the aged brain and can lead to cognitive impairments, increased symptoms from medical illness, higher utilization of health care services and increased rates of suicide and nonsuicide mortality. Therefore, it is very important to make an early diagnosis and a suitable pharmacological treatment, not only for resolving the acute episode, but also for preventing relapse and enhancing the quality of life. Age-related changes in pharmacokinetics and in pharmacodynamics have to be kept into account before prescribing an antidepressant therapy in an old patient. In this paper some of the most important and tolerated drugs in the elderly are reviewed. Tricyclic antidepressants have to be used carefully for their important side effects. Nortriptyline, amytriptiline, clomipramine and desipramine as well, seem to be the best tolerated tricyclics in old people. Second generation antidepressants are preferred for the elderly and those patients with heart disease as they have milder side effects and are less toxic in overdose and include the so called atypicals, such as selective serotonin reuptake inhibitors, serotonin noradrenalene reuptake inhibitors and noradrenaline reuptake inhibitors. Monoamine oxidase (MAO) inhibitors are useful drugs in resistant forms of depression in which the above mentioned drugs have no efficacy; the last generation drugs (reversible MAO inhibitors), such as meclobemide, seem to be very successful. Mood stabilizing drugs are widely used for preventing recurrences of depression and for preventing and treating bipolar illness. They include lithium, which is sometimes used especially to prevent recurrence of depression, even if its use is limited in old patients for its side effects, the anticonvulsants carbamazepine and valproic acid. Putative last generation mood stabilizing drugs include the dihydropyridine L-type calcium channel blockers and the anticonvulsants phenytoin, lamotrigine, gabapentin and topiramate, which have unique mechanisms of action and also merit further systematic study. Psychotherapy is often used as an adjunct to pharmacotherapy, while electroconvulsant therapy is used only in the elderly patients with severe depression, high risk of suicide or drug resistant forms.
Article
The root of Bupleurum falcatum cultivated in Japan was examined by histological and chemical means in order to clarify the distribution of saikosaponins in the various kinds of tissues and parts of the root. By means of qualitative thin-layer chromatographic—densitometric and quantitative high-performance liquid chromatographic analyses, saikosaponins, bioactive principles in the root, were found to be abundant in the outer phloem layer, especially the pericycle and its neighbouring parenchyma cells in the root. It was also found that the highest level of saikosaponins was detected in thinner root hairs and that the level decreased towards the thicker root head.
Article
To observe the effect of Xiaoyao Powder on the content changes of CRF mRNA in relative brain zone (hypothalamus, pituitary, hippocampus, cortex) in chronic restrained stress rats. RT-PCR and graphic analysis methods were applied to test the content changes of CRF mRNA in relative brain zone. The CRF-1 gene expression in hypothalamus was modulated lower in stress group and the difference was significant when compared with control group (P < 0.01). The gene expression of CRF-1 in Xiaoyao Powder group was markedly modulated lower in hypothalamus, but it was markedly modulated higher in cortex as compared with control group (P < 0.01). The gene expression of CRF-2 in Xiaoyao Powder group was higher in hypothalamus than that in stress group (P < 0.01), and it was also higher in hippocampus as compared with that in control and stress group (P < 0.01, P < 0.05 respectively). The modulation point of Xiaoyao Powder group on central neuropeptide of chronic restrained stress is respectively hypothalamus, pituitary, hippocampus and cortex. The modulating target is hypothalamus, the limbic system and the cortex center. It can be suggested that medicine of smoothing the liver simultaneously have poly-target and dual-modulating action and been involved in the integration function of nerve-endocrine-immune net.
Article
Many studies have shown that Bupleurum falcatum (BF), which is widely used in the treatment of various psychosomatic diseases in traditional Oriental medicine, is an effective therapeutic intervention for memory impairment. The purpose of this study was to examine the effect of BF on stress-induced alterations in learning and memory in rats using the Morris water maze (MWM) and elevated plus maze (EPM) behavioral tests. In addition, we examined the effects of BF treatment on the cholinergic system, as indicated by changes in neuronal choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) immunoreactivity in the hippocampus. BF (150, 300, or 600 mg/kg) was administered orally 30 min before exposure to repeated immobilization (IMO) stress (4 h/d for 14 d). The BF treatment produced a significant improvement in escape latency (time required to find the platform) in the MWM, and it also produced an anxiolytic-like effect in the EPM. Consistent with the behavioral data, BF treatment significantly attenuated the IMO stress-induced loss of cholinergic immunoreactivity in the hippocampus. These findings indicate that BF has a protective effect against repeated IMO stress-induced neuronal and cognitive impairments, and they suggest that BF may be useful in the treatment of stress-induced memory impairment.
Article
Male Sprague-Dawley rats were given 0.407 mmoles/kg of D,l-α-methyl-p-tyrosine methylester HCl (H44/68; α-MT) at eleven time-points between 0–24h, or 8 doses between 0.013–1.628 mmoles/kg of the drug at 1 h before i. v. injection of 160 μCi tyrosine-2,6-3H. The rats were killed 15 min after tyrosine-3H and brain α-MT, tyrosine and catecholamines (endogenous and labelled), and plasma α-MT and tyrosine (-3H) were chromatographically isolated before being assayed spectrophotofluorimetrically (endogenous) or by liquid scintillation methods (labelled compounds). A delayed penetration of α-MT from plasma into brain, different elimination rates of α-MT in plasma and brain, and decreasing brain/plasma drug concentration on increasing α-MT dosages indicated, that α-MT in brain and plasma belong to different pharmacokinetic compartments. The endogenous levels of catecholamines in the time-response experiment, declined to a minimum 4 h after α-MT administration, where the dopamine level was 38% and the noradrenaline level 51% of the saline controls. Kinetic data of the catecholamine elimination is given. In the dose-response experiment the decrease in the endogenous catecholamine levels was doserelated up to 0.407 mmoles/kg of α-MT, with no further decline on higher doses. The maximal inhibition of brain catecholamine synthesis occurred within 30 min after α-MT administration and the inhibition correlated better with the brain than with plasma α-MT content. The inhibition was dose-related with a maximal synthesis inhibition of 95% for dopamine and 80% for noradrenaline at the highest dose of α-MT. The duration of synthesis inhibition and storage depletion were shorter for noradrenaline (12 h) than for dopamine (16 h). Further, the ED50 for synthesis inhibition of dopamine (0.057 mmoles/kg) was half of the ED50 for synthesis inhibition of noradrenaline (0.117 mmoles/kg). This might suggest different sensitivities towards α-MT or different availabilities of α-MT in the two neuron populations. At the three highest doses of α-MT there were signs of interference with the uptake process for tyrosine from plasma into the brain. This was indicated by increased plasma levels and decreased brain levels of tyrosine (-3H).
Article
Several metabolic actions of saikosaponins isolated from the root of Bupleurum falcatum L. were examined using albino rats. Hepatic protein synthesis from leucine-14C(U) was enhanced. Glycogen content in the liver was increased, but oxidation of glucose-14C(U) in the liver was not changed. Elevation of plasma levels of cholesterol, triglycerides and p-ospholipids by cholesterol feeding was reduced. Although hepatic lipogenesis and cholesterogenesis from acetate-1-14C of glucose-14C(U) were stimulated, the elimination of i.p. injected cholesterol-4-14C from plasma was acclerated. Fecal excretion of i.p. injected cholesterol-4-14C, expressed as total-14C including bile acids-14C and neutral sterols-14C, was increased. Among the saikosaponins isolated from Bupleurum falcatum L., saikosaponins a and d, but not c, had metabolic actions as well as anti-inflammatory action. These metabolic actions and anti-inflammatory action of saikosaponins may confirm the clinical application of Bupleurum falcatum L, which has been widely used in the prescriptions of the oriental medicine, and may suggest possible mechanisms for the actions of its active principles.
Article
Effects of saikosaponins and their genins on nonspecific resistance against Pseudomonas aeruginosa and Listeria monocytogenes infections were investigated. When mice were administered intraperitoneally (i.p.) saikosaponins one day before i.p. infection with P. aeruginosa, saikosaponins a and d induced a marked enhancement of nonspecific resistance at a dose of 10 micrograms/mouse. Also, saikogenin D, a secondary metabolite of saikosaponin d, showed an enhancing effect. The most effective condition for enhancing the nonspecific resistance was i.p. administration of saikosaponin d one day before i.p. or intravenous (i.v.) infection with P. aeruginosa, when mice were treated i.p., i.v., or subcutaneously with saikosaponin d 1, 4 or 7 days previously. Effect of saikosaponin d was weaker than that of formalin-killed bacilli of Propionibacterium acnes and lipopolysaccharide. On the other hand, effect of saikosaponin d on enhancement of nonspecific resistance against L. monocytogenes was not seen. Effector cells participating in the enhanced protection induced by saikosaponin d may be macrophages, since macrophages were a major component in peritoneal cells obtained from mice administered i.p. saikosaponin d 1 day earlier and intracellular bactericidal activity of peritoneal macrophages against P. aeruginosa increased.
Article
The forced swimming test is reviewed. This test appears to be suitable for detecting antidepressant activity in rats but not in mice. Difference in experimental procedure may account for the different sensitivity to drugs of the two animal species.
Article
Crude saikosides are crude saponin fraction extracted from Bupleurum falcatum L. Anti-inflammatory and other pharmacological actions of this fraction are described. Crude saikosides showed a potent local irritation by topical application, but a significant decrease in dextran-induced edema of the rat paw, and increased capillary permeability in the mouse peritoneal cavity and in croton-induced granuloma pouch of the rat by the oral route. On the contrary, it did not show any inhibiting effect on carrageenin-induced edema, acetic acid-induced edema, adjuvant arthritis, and experimental liver fibrosis of the rat. In addition, it had no protective effect on histamine shock of the guinea pig and anaphylactic shock of the mouse. Crude saikosides did not affect gastric motility, but it was significantly effective in the prevention of the stress ulcer of the rat. Crude saikosides showed a strong stimulating effect in the intestinal propulsion test of the mouse. It markedly potentiated the contraction of isolated guinea pig ileum induced by acetylcholine, but not by histamine. Furthermore, crude saikosides showed a transient hypotensive action and a decrease of heart rate in the dog.
Article
Eighteen animal models of depression are reviewed in relation to three sets of validating criteria. Of the 18 models, five could only be assessed for predictive validity, seven could be assessed for predictive and face validity, and six could potentially have predictive, face and construct validity. Some traditional models (reserpine reversal, amphetamine potentiation) are rejected as invalid; the models with the highest overall validity are the intracranial self-stimulation, chronic stress and learned helplessness models in rats, and the primate separation model.
Article
The changes in rat hepatocytes that occur after a 4 days period of treatment with various kinds of saikosaponins were studied. The administration of saikosaponin a or d produced a marked decrease of microsomal enzyme activities, glucose-6-phosphatase and NADPH-cytochrome c reductase, and a significant increase of 5'-nucleotidase activity, whereas saikosaponin b1, b2 and c did not cause any change in enzyme activities. In the rats pretreated with saikosaponin, especially saikosaponin a or d, the remarkable inhibition of D-galactosamine induced hepatic injury was observed.
Article
The pharmacological actions of 7 pure Saikosaponins (a, b1, b2, b3, b4, c and d), the components of Saiko, which plays an important role in Oriental medicine, were studied with special attention to the analgesic effect in repeated cold stressed (SART stressed) mice. Single administration of 10 mg/kg of Saikosaponin (SS) in normal mice gave no analgesic effect, but the analgesic effect of b2 and c was great in SART stressed mice, and some analgesic effect was noted with a, b1, and b3 in SART stressed mice. Administration of 5 mg/kg/day of SS for 5 days in SART stressed mice gave an intense analgesic effect with b2 and c, and similar administration of a, b1, b3 and b4 also gave some analgesic effect. The inhibition of the body weight increase in SART stressed mice was counteracted in a dose-dependent manner by administration of 2.5-10 mg/kg/day of SSb2 and c for 5 consecutive days, but similar administration of d augmented the inhibition of body weight. The effect of administration of 5 mg/kg/day of SS for 5 days on the decrease of ACh-response in isolated duodenum from SART stressed mice, which were considered to be in partial vagotonia in small intestine, was studied. While c, b1, b2, b3, a and b4 were inhibitory, d was entirely ineffective. The effect of administration of SS on the increase of the ACh-response in isolated duodenum from mice stressed by restraint and water immersion, which were considered to be in partial sympathicotonia in small intestine, was also studied. An inhibitory effect was seen with d, which had been without effect in the specimen from SART stressed mice, while no effect of b2, c and a was noted, despite the positive effect in SART stressed mice. Three kinds of SS effects were distinguished, a central stimulating effect, a central inhibitory effect and a negative effect, based on the hypnotic effect on combined use with pentobarbital, result of measurement of motor activities in open field test in normal mice and experiment on electric resistance of the skin by GSR in SART stressed rats. According to the above results, particularly effects on the change of ACh-response in isolated duodenum, a classification of the action of SS was attempted.
Article
The mechanism of action of the novel antidepressant bupropion remains unclear after many years of study. A review of the relevant biochemical, in vivo brain microdialysis, electrophysiologic, behavioral, and clinical data clarifies what is known about this unique compound and suggests possible modes of action. A panel of 11 experts was convened for a conference to discuss bupropion's mechanism of antidepressant activity. Four of the panelists presented current research findings, followed by a discussion. (1) Biochemical studies suggest down-regulation of postsynaptic beta-adrenoceptors and desensitization of the norepinephrine-stimulated adenylate cyclase in the rat cortex occur only after chronic administration of very high doses of bupropion. (2) In vivo brain microdialysis studies demonstrate that, after chronic administration, there is an enhancement of bupropion-induced increases in extracellular dopamine in the nucleus accumbens. (3) Electrophysiologic data show that with acute dosing, bupropion reduces the firing rates of noradrenergic neurons in the locus ceruleus. The firing rates of dopaminergic neurons are reduced by bupropion in the A9 and A10 areas of the brain, but only at very high doses, and bupropion does not alter the firing rates of serotonergic neurons in the dorsal raphe. (4) Behavioral studies show that the most active metabolite of bupropion, hydroxybupropion (306U73), appears to be responsible for a large part of the compound's effects in animal models of antidepressant activity. (5) Clinical studies indicate that bupropion enhances noradrenergic functional activity as reflected by an increased excretion of the hydroxy metabolite of melatonin, while at the same time producing a presumably compensatory decrease in norepinephrine turnover. In one study, bupropion elevated plasma levels of the dopamine metabolite homovanillic acid in nonresponders, but not in responders. The mechanism of action of bupropion appears to have an unusual, not fully understood, noradrenergic link. The bupropion metabolite hydroxybupropion probably plays a critical role in bupropion's antidepressant activity, which appears to be predominantly associated with long-term noradrenergic effects. The mild central nervous system activating effects of bupropion appear to be due to weak dopaminergic mechanisms. There is some evidence that dopamine may contribute to bupropion's antidepressant properties. Antidepressant effects of bupropion are not serotonergically mediated.
Article
According to the theory of Traditional Chinese Medicine (TCM), 50 patients with affective disorders were typed into the categories of depressed liver resulting in fire, mild Yang deficiency and mild Yin deficiency and were treated with Xiao Yao San Jia Wei. The results are 26 patients with marked improvement, 17 patients with improvement and 7 patients with no improvement.
Article
Most hypotheses of the therapeutic mechanism of action of antidepressant drugs have focused on the role of the monoamines. We examined the effect of catecholamine depletion on antidepressant-induced remission. The tyrosine hydroxylase inhibitor alpha-methylparatyrosine and the antihistamine diphenhydramine hydrochloride were administered, during separate test sessions, to depressed patients in remission maintained with either norepinephrine reuptake inhibitors (desipramine [n = 7] or mazindol [n = 2]) or serotonin reuptake inhibitors (fluoxetine hydrochloride [n = 9] or sertraline hydrochloride [n = 1]). Because of considerable sedation associated with alpha-methylparatyrosine testing, diphenhydramine was used as an active control rather than an inactive placebo. The effects of alpha-methylparatyrosine and diphenhydramine on depression, anxiety, and plasma catecholamine metabolites were assessed. alpha-Methylparatyrosine produced similar significant decreases in plasma 3-methoxy-4-hydroxyphenylethyleneglycol and homovanillic acid levels in the treatment groups. alpha-Methylparatyrosine produced a robust increase in depressive symptoms on the Hamilton Depression Rating Scale, including depressed mood, decreased concentration, anhedonia, loss of interest, and feelings of worthlessness, helplessness, and hopelessness, in the desipramine-mazindol but not in the fluoxetine-sertraline group. Diphenhydramine had no effects on mood in either treatment group. The therapeutic effects of norepinephrine reuptake inhibitors, but not serotonin reuptake inhibitors, are reversed by catecholamine depletion. Considered with previous reports that serotonin depletion produces depressive relapses in patients in remission maintained with serotonin reuptake inhibitors, but not norepinephrine reuptake inhibitors, these findings suggest that antidepressants may not work via a single monoamine-related mechanism.
Article
Effects of the Kampo (Chinese herbal) medicines Hochu-ekki-to Yoku-kan-san and Saiko-ka-ryukotsu-borei-to, on behavioral despair and acetic acid-induced writhing were studied in mice. The Kampo medicines were administered for 14 consecutive days in the drinking water. In a behavioral despair study, mice were placed in a water tank containing a water wheel from which there was no escape for 15 min and the number of wheel rotations was counted as escape attempts. In accord with previous studies, imipramine (10 mg/kg i.p.) given daily for 3 days 10 min before testing markedly increased the number of wheel rotations. Hochu-ekki-to (60, 150 and 300 mg/kg/day) similarly increased the number of wheel rotations but the effect was not dose-dependent. Yoku-kan-san markedly increased the number of wheel rotations at lower doses (60 and 150 mg/kg/day), but decreased the number at the highest dose (300 mg/kg/day). Saiko-ka-ryukotsu-borei-to also increased the number of wheel rotations at the lowest does (60 mg/kg/day) but decreased the number at higher doses (150 and 300 mg/kg/day). In an antinociception study, all these Kampo medicines reduced the number of acetic acid-induced writhings, although the effect of Saiko-ka-ryukotsu-borei-to were not dose-dependent. These results suggests that these Kampo medicines may have antidepressive and antinociceptive properties.
Article
The present study was undertaken to investigate thoroughly the preclinical psychopharmacological profile of venlafaxine, testing a wide range of doses in animal models indicative of antidepressant-like effects. Venlafaxine was found to be active in mouse forced swimming test (at 8, 16, 32 and 64 mg/kg) and to increase spontaneous locomotor activity (at 16, 32 and 64 mg/kg). Venlafaxine antagonised apomorphine-induced (16 mg/kg) hypothermia (at 2, 4, 8, 16, 32 and 64 mg/kg). Pretreatment with PCPA significantly attenuated the anti-immobility effects of venlafaxine (8 and 16mg/kg; P< 0.01) in the mouse forced swimming test. Venlafaxine at a dose of 32 mg/kg remained active, despite PCPA pretreatment. DSP-4 significantly attenuated the anti-immobility effects of venlafaxine (16 mg/kg; P < 0.05), whereas venlafaxine at 32 mg/kg remained active, despite DSP-4 pretreatment. Venlafaxine was active in the forced swimming test when administered at sub-effective doses in combination with (+/-) pindolol (venlafaxine: 1 and 2 mg/kg), RU 24969 (venlafaxine: 1, 2 and 4 mg/kg), 8-OH-DPAT (venlafaxine: 4 mg/kg), clonidine (venlafaxine: 1, 2 and 4 mg/kg), lithium (venlafaxine: 1, 2, and 4 mg/kg) and quinine (venlafaxine: 1 and 2 mg/kg). Prior administration with NAN-190 antagonised the anti-immobility effects of venlafaxine (8, 16 and 32 mg/kg). Interaction studies did not induce changes in locomotor activity. The results of the present study indicated that, at low doses, venlafaxine inhibited serotonin reuptake, while at higher doses it inhibited both serotonin and noradrenaline reuptake.