Herbal formula SYJN increases neurotrophin-3 and nerve growth factor expression in brain regions of rats exposed to chronic unpredictable stress

Aim of the study

SYJN is a Chinese herbal formula that contains four herbs: Bupleurum chinense DC., Curcuma aromatica Salisb., Perilla frutescens (L.) Britt., and Acorus tatarinowii Schott. Previous studies conducted in our laboratory have revealed an antidepressant-like effect of the formula in chronic unpredictable stress (CUS)-induced depression model in rats. The present study aimed to investigate whether neurotrophin-3 (NT-3) and nerve growth factor (NGF) are involved in the antidepressant-like action of SYJN by using the same depressive model in rats.

Materials and methods

Rats were subjected to an experimental setting of CUS. The mechanism underlying the antidepressant-like action of SYJN was examined by measuring protein and mRNA expression of NT-3 and NGF in brain tissues of CUS-exposed rats.

Results

The results showed that NT-3 protein and mRNA expression in the hippocampus and frontal cortex were significantly decreased in CUS-treated rats. CUS treatment also significantly decreased NGF protein and mRNA expression in the frontal cortex of the animals. Daily intragastric administration of SYJN (1300 or 2600 mg/kg/day) during the 4 weeks of CUS significantly suppressed these changes induced by CUS.

Conclusion

The results suggest that the antidepressant-like activity of SYJN is likely mediated by the increases in NT-3 and NGF expression in brain tissues.     

Effects of peony glycosides on mice exposed to chronic unpredictable stress: Further evidence for antidepressant-like activity

Ethnopharmacology relevance

Peony, the processed root of Paeonia lactiflora Pall. (Ranunculaceae), is a component herb of many traditional formulae for the treatment of depression-like disorders.

Aim of the study

The present study aimed to investigate whether the total glycosides of peony (TGP) could prevent depression induced by chronic stress.

Materials and methods

Mice were subjected to an experimental setting of chronic unpredictable stress (CUS). The effect of TGP treatment on CUS-induced depression was examined by measuring behavioral and neurochemical parameters of depression and the antioxidant status of brain tissue.

Results

CUS-induced depression, as indicated by a significant increase in immobility time in the tail suspension test, was associated with increases in the activities of monoamine oxidases, depletion of reduced glutathione, and an increase in malondialdehyde level, in mice brains. TGP treatment alleviated the extent of CUS-induced depression and the associated impairment of antioxidant status in the mouse brain.

Conclusion

The results suggest that TGP alleviates depression induced by chronic unpredictable stress. The antidepressant-like activity of TGP is probably mediated by inhibition of monoamine oxidases and the attenuation of oxidative stress in mouse brain.     

Ethanol extracts from Hemerocallis citrina attenuate the decreases of brain-derived neurotrophic factor,TrkB levels in rat induced by corticosterone administration

Ethnopharmacological relevance

Hemerocallis citrina, a traditional herbal medicine, has been used for the improvement of behavioral and emotional status in Eastern-Asia countries.

Aim of the study

Our previous studies have demonstrated that the ethanol extracts of H. citrina flowers (HCE) reversed the behavioral alterations and monoamine neurotransmitter dysfunctions in stressed mice. However, the relation of its antidepressant-like action with neurotrophic molecular expressions remains unknown.

Materials and methods

To clarify this, we explored the effect of HCE (32.5, 65, 130 mg/kg, p.o.) on the behavior, brain-derived neurotrophic factor (BDNF) and its receptor (TrkB) in depression-like rats induced by exogenous administration of the stress hormone corticosterone (40 mg/kg, s.c.).

Results

It was observed that repeated administration of corticosterone induced an elevation on the serum corticosterone levels, which caused the abnormalities observed in the sucrose preference test and forced swimming test (FST). Administration of HCE (65 and 130 mg/kg) reversed the changes above and up-regulated the BDNF and TrkB receptor protein expressions in the brain region of frontal cortex and hippocampus.

Conclusion

These findings confirm that HCE produce an antidepressant-like effect in corticosterone-induced depression-like model of rats and this effect is at least partly mediated by BDNF-TrkB signaling in the frontal cortex and hippocampus.     

Ethanol extracts from Hemerocallis citrina attenuate the upregulation of proinflammatory cytokines and indoleamine 2,3-dioxygenase in rats

Ethnopharmacological relevance

Hemerocallis citrina, a traditional herbal medicine, has been used for the improvement of behavioral and emotional status in Eastern-Asia countries. Previous studies in our laboratory demonstrated that ethanol extracts from Hemerocallis citrina (HCE) enhanced monoamines and brain-derived neurotrophic factor (BDNF) in depression-like model of rodents.

Materials and methods

The present study extends earlier works on the role of anti-inflammation in regulating the antidepressant-like actions of HCE in rats exposed to chronic unpredictable mild stress (CUMS). Frontal cortex and hippocampal proinflammatory cytokines levels and indoleamine 2,3-dioxygenase (IDO) activity were measured after 4-week HCE treatment in the CUMS an control rats.

Results

Chronic administration of HCE reversed the decreased sucrose preference in sucrose preference test. In addition, we also found that HCE inhibited interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) expression, as well as IDO activity in frontal cortex and hippocampus, which were increased in rats exposed to CUMS.

Conclusions

Combining with our previous studies, our present finding suggests that the anti-inflammatory property of HCE might play a crucial role in its antidepressant-like effect through, at least in part, the restoration or improvement of monoaminergic and neurotrophin systems.     

Antidepressant-like action of the bark ethanolic extract from Tabebuia avellanedae in the olfactory bulbectomized mice

Ethnopharmacological relevance

Tabebuia avellanedae Lorentz ex Griseb is a plant employed in tropical America folk medicine for the treatment of several diseases, including depressive disorders.

Aim of the study

To investigate the ability of Tabebuia avellanedae ethanolic extract (EET) administered chronically to cause an antidepressant-like effect in the tail suspension test (TST), a predictive test of antidepressant activity, and to reverse behavioral (hyperactivity, anhedonic-like behavior and increased immobility time in the TST) and biochemical changes induced by olfactory bulbectomy (OB), a model of depression, in mice.

Materials and methods

Mice were submitted to OB to induce depressive-related behaviors, which were evaluated in the open-field test (hyperactivity), splash test (loss of motivational and self-care behavior indicative of an anhedonic-like behavior) and TST (increased immobility time). Phosphorylation levels of Akt, GSK-3β, ERK1/2 and CREB, as well as BDNF immunocontent, were evaluated in the hippocampus of bulbectomized mice or sham-operated mice treated for 14 days by p.o. route with EET or vehicle.

Results

EET (10 and 30 mg/kg) given 14 days by p.o route to mice reduced the immobility time in the TST without altering locomotor activity, an indicative of an antidepressant-like effect. EET per se increased both CREB (Ser¹³³) and GSK-3β (Ser⁹) phosphorylation (at doses of 10–30 and 30 mg/kg, respectively) in sham-operated mice. OB caused hyperactivity, loss of motivational and self-care behavior, increased immobility time in the TST and an increase in CREB and ERK1 phosphorylation, as well as BDNF immunocontent. EET abolished all these OB-induced alterations except the increment of CREB phosphorylation. Akt (Ser⁴⁷³) and ERK2 phosphorylation levels were not altered in any group.

Conclusions

EET ability to abolish the behavioral changes induced by OB was accompanied by modulation of ERK1 and BDNF signaling pathways, being a promising target of EET. Results indicate that this plant could constitute an attractive strategy for the management of depressive disorders, once more validating the traditional use of this plant.     

Herbal formula SYJN protect PC12 cells from neurotoxicity induced by corticosterone

Aim of the study

SYJN is a Chinese herbal formula, containing four herbs: Bupleurum chinense DC., Curcuma aromatica Salisb., Perilla frutescens (Linn.) Britt. and Acorus tatarinowii Schott. Previous studies on the formula in our laboratory revealed an antidepressant-like effect on animal models of behavioral despair. However,the mechanisms underlying such antidepressant-like effect are yet to be understood. The aim of this work was to verify the previously established antidepressant-like effects on cell level using corticosterone-induced neurotoxicity in rat pheochromocytoma (PC12) cells to see if SYJN possesses any neuroprotective properties.

Materials and methods

PC12 cells were treated with 200 μM corticosterone in the absence or the presence of various concentrations of SYJN for 48 h. Then, cell viability, apoptosis, intracellular Ca²⁺ ([Ca²⁺]i) concentration and caspase-3 activity were determined.

Results

Following the exposure of PC12 cells to 200 μM corticosterone for 48 h, there were reductions in cell survival rate but increases in lactate dehydrogenase (LDH) release. In parallel, corticosterone caused significant elevations in DNA fragmentation, [Ca²⁺]i concentration and caspase-3 activity. However, when the PC12 cells were incubated with SYJN at different concentrations (10, 50 and 100 mg/L) in the presence of 200 μM corticosterone for 48 h, the above effects were evidently alleviated in a dose-dependent manner.

Conclusion

SYJN could generate a neuroprotective effect on corticosterone-induced neurotoxicity in PC12 cells, suggesting a possible action pathway of SYJN in vivo by decreasing the [Ca²⁺]i concentration and caspase-3 activity.     

Essential oil of Perilla frutescens-induced change in hippocampal expression of brain-derived neurotrophic factor in chronic unpredictable mild stress in mice

Ethnopharmacological relevance

Perilla frutescens (Perilla leaf), a traditional Chinese medicinal herb, has been used for centuries to treat various conditions including depression. A previous study of the authors demonstrated that essential oil of Perilla frutescens (EOPF) attenuated the depressive-like behavior in mice.

Aim of the study

This study was undertaken to explore the dynamic change of behaviors and brain-derived neurotrophic factor (BDNF) expression induced by chronic unpredictable mild stress (CUMS), and improved by EOPF.

Materials and methods

Four separate CUMS experimental groups (1-week, 2-week, 3-week and 4-week treatment) were treated with EOPF (3 mg/kg and 6 mg/kg, p.o.) or fluoxetine (20 mg/kg, p.o.), followed by sucrose preference, locomotor activity, immobility and hippocampal BDNF measurement.

Results

EOPF, as well as fluoxetine, restored the CUMS-induced decreased sucrose preference and increased immobility time, without affecting body weight gain and locomotor activity. Furthermore, CUMS (3 or 4-week) produced a reduction in both BDNF mRNA and protein expression in the hippocampus, which were ameliorated by EOPF (4-week) and fluoxetine (3 or 4-week) treatment.

Conclusion

These results presented here show that BDNF is expressed depending on length of CUMS procedure and EOPF administration. And this study might contribute to the underlying reason for the slow onset of antidepressant activity in clinic.     

Scutellarin and caffeic acid ester fraction,active components of Dengzhanxixin injection,upregulate neurotrophins synthesis and release in hypoxia/reoxygenation rat astrocytes

Ethnopharmacological relevance

Scutellarin (Scu) and caffeic acid ester fraction (Caf), the extracts from the traditional Chinese herb, Erigeron breviscapus, are known to ameliorate post ischemic neuronal dysfunction.

Aim of the study

Neurotrophic factors (NTFs) are essential for neuronal growth and survival. We explored the neuroprotective effect of Scu and Caf by synthesis and release of NGF, BDNF and GDNF in rat astrocytes exposed to hypoxia/reoxygenation and MACO rats. And the neuroprotection of Scu and Caf was also explored.

Materials and methods

The primary rat astrocytes were cultured in vitro. The temporal mRNA and protein expression profile during hypoxia/reoxygenation were analyzed using real-time RT-PCR and ELISA. The expression of p-CREB, p-Akt, p-MAPKs and Bax were analyzed by western blotting. Cell viability of neuro-2A was measured using CCK-8 and cell cytotoxicity was measured with LDH release.

Results

During hypoxia/reoxygenation a similar decrease pattern of NTFs (NGF, BDNF and GDNF) was observed in both mRNA and protein; Scu and Caf enhanced the expressions of NGF, BDNF and GDNF mRNA and protein in astrocytes under hypoxia/reoxygenation condition. CREB and Akt, but not MAPKs ( p-JNK, p-ERK1/2 and p-38) may be involved in the expression of NTFs. Concomitantly, conditioned medium from astrocytes which was treated by Scu or Caf after hypo3 h/Reox24 h significantly reduced neurotoxicity compared with conditioned medium from hypo3 h/Reox24 h astrocytes alone, and they show the tendency of increased neurons viability accompanied with Bax changes.

Conclusions

These results indicate that the neuroprotective effect of Scu and Caf might be mediated, at least in part, via a stimulation of the production and release of NTFs through p-CREB and p-Akt signaling. Furthermore, Scu and Caf could antagonistic the hypoxia induced toxicity through astrocytes conditioned medium. Those results suggested that Scu and Caf might have therapeutic potential for stroke.     

Subchronic administration of Trichilia catigua ethyl-acetate fraction promotes antidepressant-like effects and increases hippocampal cell proliferation in mice

Ethnopharmacological relevance

Trichilia catigua preparations have been popularly used in Brazil as a tonic for the treatment of fatigue, stress, impotence, and memory deficits. We recently demonstrated an antidepressant-like effect of acute administration of the Trichilia catigua ethyl-acetate fraction (EAF) in mice. The aim of the present study was to evaluate whether subchronic Trichilia catigua EAF administration maintains its antidepressant-like effects and whether these effects are related to hippocampal neurogenesis.

Material and methods

Trichilia catigua EAF (200 and 400 mg/kg) was orally administered to mice for 14 day. The animals were tested in the forced swim test (FST) or tail suspension test (TST). After behavioral testing, the animals received bromodeoxyuridine (BrdU; 200 mg/kg, i.p.) and were euthanized 24 h, 7 day, or 15 day later. The brains were assayed for BrdU and doublecortin (DCX) immunohistochemistry to detect cell proliferation/survival and neurogenesis, respectively.

Results

Subchronic administration of 400 mg/kg Trichilia catigua EAF promoted antidepressant-like effects in mice in both the FST and TST. The antidepressant-like effect was accompanied by an increase in cell proliferation in the dentate gyrus (DG) of the hippocampus 24 h after the treatments were discontinued. This proliferative effect, however, did not influence cell survival or neurogenesis because no change in the number of BrdU- or DCX-positive cells was detected 7 or 15 day after the last EAF administration compared with controls.

Conclusions

Trichilia catigua EAF produced antidepressant-like effects and induced hippocampal cell proliferation in mice. The results contribute information on the pharmacological and molecular mechanisms involved in the antidepressant-like effect of Trichilia catigua EAF.     

Rosmarinus officinalis L. hydroalcoholic extract,similar to fluoxetine,reverses depressive-like behavior without altering learning deficit in olfactory bulbectomized mice

Ethnopharmacological relevance

Rosemary, Rosmarinus of?cinalis L., has several therapeutic applications in folk medicine for the treatment of a wide range of diseases, including depression.

Aim of the study

To evaluate the ability of Rosmarinus of?cinalis hydroalcoholic extract (ROHE), as compared to the positive control fluoxetine, to reverse behavioral (hyperactivity, anhedonic behavior and learning deficit in water maze) and biochemical alterations (serum glucose level and acetylcholinesterase, AChE, activity) induced by an animal model of depression, the olfactory bulbectomy (OB) in mice.

Materials and methods

Locomotor and exploratory behavior was assessed in the open-field, novel object and novel cage tests, anhedonic behavior was assessed in the splash test; cognitive deficits were evaluated in the water maze task. For the first set of experiments, ROHE (10–300 mg/kg) or fluoxetine (10 mg/kg) was administered once daily (p.o.) for 14 days after OB and the behavioral tests were performed. For the second set of experiments, serum glucose and hippocampal and cerebrocortical AChE activity were determined in OB and SHAM-operated mice treated orally with ROHE (10 mg/kg), fluoxetine (10 mg/kg) or vehicle.

Results

ROHE (10–300 mg/kg), similar to fluoxetine, reversed OB-induced hyperactivity, increased exploratory and anhedonic behavior. OB needed significantly more trials in the training session to acquire the spatial information, but they displayed a similar profile to that of SHAM mice in the test session (24 h later), demonstrating a selective deficit in spatial learning, which was not reversed by ROHE or fluoxetine. A reduced serum glucose level and an increased hippocampal AChE activity were observed in bulbectomized mice; only the latter effect was reversed by fluoxetine, while both effects were reversed by ROHE.

Conclusions

ROHE exerted an antidepressant-like effect in bulbectomized mice and was able to abolish AchE alterations and hypoglycemia, but not spatial learning deficit induced by OB. Overall, results suggest the potential of Rosmarinus officinalis for the treatment of depression, validating the traditional use of this plant.     

Involvement of monoaminergic systems in the antidepressant-like effect of Eugenia brasiliensis Lam. (Myrtaceae) in the tail suspension test in mice

Ethnopharmacological relevance

Several species of Eugenia L. are used in folk medicine for the treatment of various diseases. Eugenia brasiliensis is used for the treatment of inflammatory diseases, whereas Eugenia. uniflora is used for the treatment of symptoms related to depression and mood disorders, and is used in Brazil by the Guarani Indians as a tonic stimulant.

Aim of the study

To investigate the antidepressant-like effect of hydroalcoholic extracts of different plant species of genus Eugenia and to characterize the participation of the monoaminergic systems in the mechanism of action of the specie that afforded the most prominent antidepressant-like efficacy.

Materials and methods

In the first set of experiments, the effects of hydroalcoholic extracts of Eugenia beaurepaireana, Eugenia brasiliensis, Eugenia catharinae, Eugenia umbelliflora and Eugenia uniflora and the antidepressant fluoxetine (positive control) administered acutely by p.o. route were evaluated in the tail suspension test (TST) and locomotor activity was assessed in the open-field test in mice. In the second set of experiments, the involvement of the monoaminergic systems in the antidepressant-like activity of Eugenia brasiliensis was evaluated by treating mice with several pharmacological agonists and antagonists. The effects of the combined administration of sub-effective doses of Eugenia brasiliensis and the antidepressants fluoxetine, imipramine and bupropion were also evaluated.

Results

The administration of the extracts from Eugenia brasiliensis, Eugenia catharinae and Eugenia umbelliflora, but not Eugenia beaurepaireana and Eugenia uniflora, exerted a significant antidepressant-like effect, without altering locomotor activity. The behavioral profile was similar to fluoxetine. Pre-treatment of mice with ketanserin, haloperidol, SCH23390, sulpiride, prazosin and yohimbine prevented the reduction of immobility time induced by Eugenia brasiliensis. Treatment with sub-effective doses of WAY100635, SKF38393, apomorphine, phenylephrine, but not clonidine, combined with a sub-effective dose of Eugenia brasiliensis decreased the immobility time in the TST. Furthermore, the combined administration of sub-effectives doses of Eugenia brasiliensis with fluoxetine, imipramine and bupropion produced an antidepressant-like effect.

Conclusions

This study show, for the first time, the antidepressant-like effect of species of the genus Eugenia, especially Eugenia brasiliensis, whose effects in the TST seem to be mediated by serotoninergic (5-HT_1A and 5-HT₂ receptors), noradrenergic (α₁-adrenoceptor) and dopaminergic (dopamine D₁ and D₂ receptors) systems.     

Protective effects of aqueous extract from Acanthopanax senticosus against corticosterone-induced neurotoxicity in PC12 cells

Ethnopharmacological relevance

Acanthopanax senticosus, classified into the family of Araliaceae, has been known for thousands of years as a remedy and is used to treat various diseases in traditional Chinese medicine system including hypertension, ischemic heart disease and hepatitis.

Aim of the study

This study aimed to examine the protective effects of aqueous extract from Acanthopanax senticosus (ASE) on corticosterone-induced neurotoxicity and its possible mechanisms, using PC12 cells as a suitable in vitro model of depression.

Materials and methods

In this paper, PC12 cells were treated with 200 μM of corticosterone in the absence or presence of ASE in varying concentrations for 24 h. Then, cell viability was measured by MTT assay. The release amount of lactate dehydrogenase (LDH) was quantified using LDH assay kit. Apoptosis of PC12 cells was measured by Annexin V-FITC and PI labeling. The intracellular Ca²⁺ content was tested by fluorescent labeling. The mRNA level of brain-derived neurotrophic factor (BDNF) was examined by real-time RT-PCR, and the expression of cAMP response element binding protein (CREB) was determined by western blotting.

Results

The results showed that treatment with 200 μM of corticosterone could induce cytotoxicity in PC12 cells. However, different concentrations of ASE (50, 100, 200, and 400 μg/mL) significantly increased the cell viability, decreased the LDH release, suppressed the apoptosis of PC12 cells, attenuated the intracellular Ca²⁺ overloading, up-regulated the BDNF mRNA level and CREB protein expression compared with the corresponding corticosterone-treated group.

Conclusion

The present results suggest that ASE exerts a neuroprotective effect on corticosterone-induced neurotoxicity in PC12 cells, which may be one of the acting mechanisms that accounts for the in vivo antidepressant activity of ASE.     

Antidepressant activity of Litsea glaucescens essential oil: Identification of β-pinene and linalool as active principles

Ethnopharmacological relevance

Litsea glaucescens (Lauraceae) has been used in Mexican Traditional Medicine to relieve illness related to central nervous system, such as epilepsy, fright and sadness. In this study, L. glaucescens essential oil properties on central nervous system were evaluated in mice using different behavioral tests.

Materials and methods

The essential oil was obtained by hydrodistillation and analyzed by GC/MS. Identification of major compounds was also carried out by comparison with authentic samples. The psychopharmacological profile of L. glaucescens essential oil, and some its major compounds, were evaluated in mice using several experimental models: forced swimming test (FST: Antidepressant-like activity), open field test (OFT: Spontaneous locomotor activity), elevated plus-maze (EPM: Anxiolytic-like activity), exploratory cylinder (ECT: Sedative-like activity), rotarod (motor coordination) and traction performance (myo-relaxant effect) the essential oil and active principles was administered intraperitoneally.

Results

The essential oil showed antidepressant-like activity at doses of 100 and 300 mg/Kg. The monoterpenes β-pinene and linalool were identified as the two main active principles of the essential oil, and showed antidepressant-like and sedative-like activity. Eucalyptol, limonene and α-pinene they did not show antidepressant-like activity, and were not further tested.

Conclusions

L. glaucescens essential oil showed antidepressant activity, β-pinene and linalool were identified as its active principles. These results support the use of L. glaucescens in Mexican Traditional Medicine for the treatment of sadness.     

Cycloartane triterpenoid saponins from water soluble of Passiflora edulis Sims and their antidepressant-like effects

Ethnopharmacological relevance

Various species of genus Passiflora have been used as traditional folk medicines owing to their sedative and anti-hypertensive properties. Passiflora edulis Sims most widely grown in the warm temperate for their fragrant fruits and their twigs and leaves are used as a folk medicine for treating both anxiety and nervousness in American countries. The present study was to evaluate the antidepressant-like effect and the active components of this plant.

Materials and methods

The alcohol extracts of the stems (PES, 10 and 2 g/kg of the plant materials) and leaves (PEL, 10 and 2 g/kg of the plant materials) of Passiflora edulis Sims were orally administered to mice for 7 day. The animals were tested in the forced swim test (FST) and tail suspension test (TST). After behavioral assay of ethanol extract, phytochemical research of the stems and leaves (5.7 kg) of Passiflora edulis Sims were developed and further bioactive verification of monomeric compounds were conducted.

Results

There are mainly cycloartane triterpenoids and their saponins isolated from this plant, including two new cycloartane triterpenoid saponins named cyclopassifloside ХII (1) and ХIII (2), together with six known cycloartane triterpenoids, cyclopassifloic acids B and E, cyclopassiflosides II, VI, IX and XI. The ethanol extract of Passiflora edulis Sims together with isolated compounds cyclopassiflosides IX and XI may possess antidepressant-like effect.

Conclusions

Cycloartane triterpenoid was one of the main compositions of Passiflora edulis Sims and possess antidepressant-like activity.     

The effect of Chaihu-Shugan-San and its components on the expression of ERK5 in the hippocampus of depressed rats

Ethnopharmacological relevance

Chaihu-Shugan-San (CSS) is a well-known, Chinese traditional medicine used to treat depression. Little is known about the antidepressant mechanism of CSS. The main aims of the this study were to evaluate the antidepressant-like effects of CSS and its components and further explore the CSS?s effect upon signal transduction of extracellular signal-regulated kinase 5 (ERK5) expressions in the hippocampus of rats with depression induced by chronic unpredicted mild stress.

Materials and methods

SD rats were randomly divided into six groups: Normal; Model; CSS; Component I; Component II; and Fluoxetine. Antidepressant-like effects of CSS and two of its constituents, Components I and II in aqueous extract, were assessed using rats exposed to chronic unpredictable mild stress (CUMS) by measuring weight change, observing the open-field test and measuring sucrose water consumption. Antidepressant mechanism were examined by measuring the effect of CSS, and two of its constituents, on extracellular signal-regulated kinase 5 (ERK5) expression, phosphorylation-ERK5 (p-ERK5), and ERK5 mRNA in the hippocampus by using western blotting and Real-time Polymerase Chain Reaction (PCR). Three preparations were prepared: (1) an aqueous extract of CSS (5.9 g/kg·d); (2) Component I (3.3 g/kg·d); and (3) Component II (2.6 g/kg·d). During the 28-day CUMS, the three preparations were intragastrically administered all three preparations. Simultaneously a parallel positive fluoxetine control group was given fluoxetine hydrochloride (1.8 mg/kg·d). Normal and Model groups were intragastrically administered with a isovolumic distilled water (4.5 ml/kg·d).

Results

Depressed rats had decreased weight gain; decreased locomotor activity as measured by the open field test; and reduced sucrose consumption. The rats? hippocampus ERK5 activation was significantly suppressed. CSS reduced the incidence of depressive-like behaviors and increased ERK5 activation in depressed rats at the same rate as fluoxetine. Component I, and II, each had only a partial effect on the depression indicators measured.

Conclusions

CSS aqueous extract has antidepressant-like effects on CUMS-induced depression model rats. The antidepressant effect of CSS is greater than that of either the two separate components measured. CSS?s antidepressant mechanism may be mediated by reversing the stress-induced disruption of ERK5 activity.     

Antidepressant-like effect of Salvia sclarea is explained by modulation of dopamine activities in rats

Aim of the study

The purpose of the present study was to screen aromatic essential oils that have antidepressant effects to identify the regulatory mechanisms of selected essential oils.

Materials and methods

The antidepressant effects of essential oils of Anthemis nobilis (chamomile), Salvia sclarea (clary sage; clary), Rosmarinus officinalis (rosemary), and Lavandula angustifolia (lavender) were assessed using a forced swim test (FST) in rats. Rats were treated with essential oils by intraperitoneal injection or inhalation. Serum levels of corticosterone were assessed by enzyme-linked immunosorbent assay (ELISA).

Results

Among the essential oils tested, 5% (v/v) clary oil had the strongest anti-stressor effect in the FST. We further investigated the mechanism of clary oil antidepression by pretreatment with agonists or antagonists to serotonin (5-HT), dopamine (DA), adrenaline, and GABA receptors. The anti-stressor effect of clary oil was significantly blocked by pretreatment with buspirone (a 5-HT_1A agonist), SCH-23390 (a D₁ receptor antagonist) and haloperidol (a D₂, D₃, and D₄ receptor antagonist).

Conclusions

Our findings indicate that clary oil could be developed as a therapeutic agent for patients with depression and that the antidepressant-like effect of clary oil is closely associated with modulation of the DAnergic pathway.     

Evidence of the involvement of the monoaminergic systems in the antidepressant-like effect of Aloysia gratissima

Ethnopharmacological relevance

Aloysia gratissima (Verbenaceae) is an aromatic plant distributed in South America and, employed in folk medicine for the treatment of nervous systems illness, including depression. The neuroprotective and antidepressant-like activities of the aqueous extract of Aloysia gratissima (AE) administered orally has already been demonstrated.In this study the involvement of monoaminergic systems in the antidepressant-like effect of the AE was investigated.

Materials and methods

The implication of the monoaminergic systems in the antidepressant-like activity of Aloysia gratissima was evaluated using different pharmacological antagonists that were administered previously to the acute oral administration of AE (10 mg/kg). The antidepressant-like effect was assessed in the TST and locomotor activity was evaluated in the open-field test in mice.

Results

The anti‐immobility effect elicited by AE in the TST was prevented by the pre-treatment of mice with the antagonists, NAN‐190 (5‐HT_1A receptor), ketanserin (5‐HT_2A/2C receptor), prazosin (α₁‐adrenoceptor), yohimbine (α₂‐adrenoceptor), SCH23390 (dopamine D₁ receptor), or sulpiride (dopamine D₂ receptor).

Conclusions

These results indicate that the antidepressant‐like effect of AE in the TST is dependent on its interaction with the serotonergic (5‐HT_1A and 5‐HT_2A/2C), noradrenergic (α₁ and α₂₋adrenoceptors) and dopaminergic (D₁ and D₂ receptors) systems, suggesting that this specie might act as a new potential resource for developing antidepressants to treat depressive disorders.     

Antidepressant-like effect of the ethanolic extract from Suanzaorenhehuan Formula in mice models of depression

Ethnopharmacological relevance

Suanzaorenhehuan Formula (SHF) is a Chinese herbal formula for the treatment of depression-like disorders. It contains four herbs: Semen Ziziphi spinosae, Cortex Albiziae, Radix Paeoniae Alba and Semen Platycladi. The present study is to investigate the antidepressant-like effect of the ethanolic extract of SHF and its possible mechanisms.

Materials and methods

Mouse models of depression including the tail suspension test (TST), forced swimming test (FST) and chronic unpredicted mild stress (CUMS) were used to evaluate the effects of SHF extract. The mechanisms were examined by measuring monoamine neurotransmitters in mice hippocampus and frontal cortex, testing monoamine oxidase enzyme (MAO) activities in brain of CUMS-exposed mice.

Results

After one-week treatment, SHF extract (50, 100 and 200 mg/kg) induced a significant decrease on immobility time in TST. After two-week treatment, SHF extract (50, 100 and 200 mg/kg) led to a reduction in the immobility period in TST and FST. The 5-HT levels in mice hippocampus were increased only after 200 mg/kg SHF extract treatment. The noradrenaline (NE) levels were increased after 200 mg/kg SHF extract treatment in mice hippocampus and frontal cortex. SHF extract (50, 100 and 200 mg/kg) significantly inhibited monoamine oxidase-A (MAO-A) and monoamine oxidase-B (MAO-B) after 21-day CUMS exposure.

Conclusion

These findings demonstrated that ethanolic SHF extract produced an antidepressant-like effect and the mechanism of action involves the serotonergic, noradrenergic and monoamine oxidase enzyme systems although underlying mechanism still remains to be further elucidated.     

Antidepressant-like activity of the aqueous extract of Allium macrostemon in mice

Aim of the study

The aim of this study was to identify the effects of water extracts of Allium macrostemon Bunge (AM-W), a traditional herb, in mice.

Materials and methods

The antidepressant-like activities of AM-W were evaluated through behavioral despair in forced swimming test and tail suspension test. To elucidate the mode of action of the antidepressant-like effects of AM-W, new born cells in the subgranular zone and the granule cell layer were analyzed by immunostaining for incorporation of 5-bromo-2-deoxyuridine (BrdU). In addition, the effects of AM-W on the expression levels of brain-derived neurotrophic factor (BDNF) were investigated by western blotting and immunohistochemistry.

Results

The administration of AM-W reduced the immobility duration in the forced swimming test and tail suspension test (100 or 200 mg/kg, P < 0.05). Sub-chronic administration of AM-W (100 or 200 mg/kg, p.o., for 14 days) increased the number of BrdU-incorporating cells. The percentage of BrdU-incorporating cells co-localized with NeuN was significantly increased after AM-W administration (100 or 200 mg/kg, P < 0.05). Moreover, the expression levels of BDNF which is reported to be associated with neurogenesis were significantly increased in the hippocampus after administration of AM-W.

Conclusions

These results suggest that AM-W may be a good antidepressant, and that its mechanism of action may be related to its positive effects on neurogenesis and BDNF release.