A Network Pharmacology-Based Study on Antidepressant Effect of Salicornia europaea L. Extract with Experimental Support in Chronic Unpredictable Mild Stress Model Mice / 中国结合医学杂志

OBJECTIVE@#To investigate the pharmacodynamic material basis, mechanism of actions and targeted diseases of Salicornia europaea L. (SE) based on the network pharmacology method, and to verify the antidepressant-like effect of the SE extract by pharmacological experiments.@*METHODS@#Retrieval tools including Chinese medicine (CM), PubMed, PharmMapper, MAS 3.0 and Cytoscape were used to search the components of SE, predict its targets and related therapeutic diseases, and construct the "Component-Target-Pathway" network of SE for central nervous system (CNS) diseases. Further, protein-protein interaction (PPI) network, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) function annotation of depression-related targets were analyzed to predict the antidepressant mechanism of SE. Chronic unpredictable mild stress (CUMS) model was used to construct a mouse model with depression-like symptoms. And the animals were randomly divided into 6 groups (n=10) including the normal group (nonstressed mice administered with distilled water), the CUMS group (CUMS mice administered with distilled water), the venlafaxine group (CUMS mice administered with venlafaxine 9.38 mg/kg), SE high-, medium-, and low-dose groups (CUMS mice administered with SE 1.8, 1.35 and 0.9 g/kg, respectively). Then some relevant indicators were determined for experimental verification by the forced swim test (FST), the tail suspension test (TST) and open-field test (OFT). Dopamine (DA) concentration in hippocampus and cerebral cortex, IL-2 and corticosterone (CORT) levels in blood, and nuclear factor E2 related factor 2 (Nrf2), kelch-like epichlorohydrin related protein 1 (Keap1), NAD(P) H dehydrogenase [quinone] 1 (NQO1) and heme oxygenase-1 (HO-1) levels in mice were measured by enzyme linked immunosorbent assay (ELISA) and Western blot respectively to explore the possible mechanisms.@*RESULTS@#The "target-disease" network diagram predicted by network pharmacology, showed that the potential target of SE involves a variety of CNS diseases, among which depression accounts for the majority. The experimental results showed that SE (1.8, 1.35 g/kg) significantly decreased the immobility period, compared with the CUMS group in FST and TST in mice after 3-week treatment, while SE exhibited no significant effect on exploratory behavior in OFT in mice. Compared with CUMS group, the SE group (0.9 g/kg) showed significant differences (P<0.05) in DA levels in the hippocampus and cerebral cortex. In addition, compared with CUMS control group, SE (1.8 g/kg) group showed a significant effect on decreasing the activities of CORT (P<0.05), and serum IL-2 level with no statistical significance. Finally, Western blot results showed that compared with the model group, Nrf2, Keap1, NQO1 and HO-1 protein expressions in SE group (1.8 g/kg) were up-regulated (all P<0.01).@*CONCLUSION@#The SE extract may have an antidepressant effect, which appeared to regulate Nrf2-ARE pathway and increased levels of DA and CORT in the hippocampus and cortex.

Antidepressant-like activity of ethanol extract of leaves of Caesalpinia pulcherrima in unstressed and stressed mice

In the present study, antidepressant-like activity of ethanol extract of leaves of Caesalpinia pulcherrima was evaluated in Swiss young male albino mice. Stress was induced in mice by subjecting them to unpredictable mild stress for 21 successive days. Ethanol extract of the leaves (100, 200 and 400 mg/ kg, p.o.) and fluoxetine (20 mg/kg, p.o.) were administered for 21 consecutive days to separate groups of unstressed and stressed mice. Ethanol extract (200 and 400 mg/kg) and fluoxetine significantly decreased immobility period of unstressed as well as stressed mice in tail suspension test (TST). However, the lowest dose (100 mg/kg) of the extract also significantly decreased immobility period of stressed mice in TST. The extract significantly restored reduced sucrose preference in stressed mice. There was no significant effect on locomotor activity of mice. Ethanol extract of the leaves significantly decreased plasma nitrite and corticosterone levels; brain MAO-A activity and MDA level; and increased brain reduced glutathione and catalase activity in unstressed as well as stressed mice as compared to their respective vehicle treated controls. Thus, ethanol extract of leaves of Caesalpinia pulcherrima showed significant antidepressant-like activity in unstressed and stressed mice probably through inhibition of brain MAO-Aactivity, reduction of oxidative stress and plasma corticosterone levels.

Evaluation of antidepressant activity of hydro-alcoholic extract of rhizomes of Nardostachys jatamansi DC per se and in combination with fluoxetine in wistar albino rats and swiss albino mice

Background: Depression is a common mental disorder results due to deficiency of neurotransmitter in the brain. Various medicinal properties of jatamansi are mentioned in Ayurveda. This study evaluated effect of hydro-alcoholic extract of rhizomes of Nordostachys jatamansi DC per se and in combination with fluoxetine in wistar albino rats and swiss albino mice.Methods: Animals of either sex were selected and randomly divided in test group. Jatamansi extract 10:1 and fluoxetine hydrochloride dissolved in distilled water were used. Animals were tested for forced swimming test, tail suspension test and locomotor after given test drug. Results were compared with control and analysed.Results: Nardostachys jatamansi DC, when given to rats showed dose dependent increase in number of rotation during forced swimming test in rats. During forced swimming test in glass jar statistically significant decrease in immobility was observed. Nardostachys jatamansi DC, when given to mice dose dependent statistically significant decrease in immobility time, swimming time and climbing observed. When given along with combination of fluoxetine it shows statistically significant difference in result, confirmed that it can have synergistic antidepressant activity. When used for locomotor activity in mice none of the test drugs significantly increase or decrease the locomotor activity.Conclusions: Jatamansi showed antidepressant like property in various tests conducted on rats and mice. It showed statistically significant result with increasing dose and had synergic effect when given along with fluoxetine.

Impact of simulated microgravity on flash electroretinogram and retinal microcirculation in adult mice / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To observe changes in the flash electroretinogram(ERG)and retinal microcirculation in mice suspended by their tails, an animal model that simulates cephalad movement of bodily fluids under conditions of microgravity.<p>METHODS: Thirty-six adult male C57BL/6J mice(36 eyes)were randomly divided into three experimental groups and three control groups. Mice in the experimental groups were tail-suspended for 15d(Group one), tail-suspended for 30d(Group two), or tail-suspended followed by returning to normal position for 30d(Group three). Three control groups were similarly fixed with a harness but kept in the normal position for corresponding periods of 15, 30, and 60d. The mice were immediately examined using scotopic ERG(including oscillatory potentials \〖OPs\〗)and fundus fluorescein angiography(FFA)<i>in vivo</i>, and subsequently sacrificed to analyze the retinal histology(methods including immunohistochemistry and TUNEL staining)<i>in vitro</i>. Independent sample <i>t</i>-test was used for data comparison between the same time-point groups.<p>RESULTS: Following 15-days' tail-suspension, scotopic ERG showed a decline in OPs, but not in the b-wave; the second OP(O2)showed an amplitude of 197±33μV, which was about 60% of the control level(<i>t</i>=-5.938, <i>P</i><0.001). Following 30-days' tail-suspension, ERG recovered, with O2 showing an average value of 264±39μV; when compared to the corresponding control group(308±41μV), no significant difference was observed(<i>t</i>=-1.887, <i>P</i>>0.05). Morphologically, only the 15-days' tail-suspended mice showed FFA with microvascular dilation and tortuosity. Rhodopsin and cone-opsin were almost normal and no apoptotic-positive signals were detected in the retinas of the three tail-suspended groups.<p>CONCLUSION: Simulating cephalad shifting of bodily fluids as under microgravity, using short-term tail-suspension can affect rodent ERG and retinal microcirculation; however, the change is reversible with no obvious permanent injury observed in the retinas.

Evaluation of antidepressant activity of l-methylfolate per se and its interaction with escitalopram in mice

Background: Depression is a worldwide illness in the current population. Low levels of L-methylfolate are linked to depression. Present study evaluates the anti-depressive activity of acute and chronic administration of L-methylfolate per se in forced swimming test (FST) and tail suspension test (TST) and its interaction with escitalopram in albino mice.Methods: For this 30 swiss albino mice were divided randomly into five groups (n=6) as group I (control,10ml/Kg, p.o) - 2% suspension of gum acacia, group II - escitalopram suspension (10mg/kg, p.o), group III- L-methylfolate suspension (3mg/kg, p.o), group IV- L-methylfolate (3mg/kg, p.o) plus escitalopram (5mg/kg, p.o), group V- L-methylfolate(3mg/kg, p.o) plus escitalopram(10mg/kg, p.o), for forced swimming test. In tail suspension test again, mice were divided in five groups as above except that the dose of L-methylfolate was reduced to 1.25mg/kg. The pharmacologically validated models forced swimming test and tail suspension test were performed in mice to evaluate acute and chronic antidepressant activity of L-methylfolate and its combination with escitalopram respectively, after performing an acute toxicity study.Results: L-methylfolate and L-methylfolate plus escitalopram (10mg/Kg and 5mg/Kg, p.o) showed acute and chronic antidepressant activity in albino mice in FST and TST respectively. In human L-methylfolate is only active form of folic acid that readily crosses the blood brain barrier and utilized by the CNS. It regulates the bioavailability of critical cofactor BH4, required by enzymes synthesizing monoamines whose deficiency leads to depression.Conclusions: Hence, this study suggests antidepresant activity of L-methylfolate per se and as adjuvant with escitalopram when initiated from initiation of antidepressant therapy. Also, L-methylfolate opens the possibility of reducing the dose of antidepressant when used as adjuvant.

The protective effect of L. siceraria against depression using behavioural despair animal models

Background: In recent years, the search for novel pharmacotherapy from medicinal plants for psychiatric illness was significantly progressed. The present study was performed to evaluate the antidepressant activity of ethanolic extract of Lagenaria siceraria in animal models.Methods: The antidepressant activity of ethanolic extract of the fruit of L. siceraria in rats was assessed using forced swim test and tail suspension test. Imipramine at 15 mg/kg was used as standard antidepressant drug.Results: The ethanolic extract of L. siceraria fruit (EELS) was significantly and dose-dependently reduced the duration of immobility after repeated treatment for 7 days in Forced swim test and Tail suspension Test. But combination of L. siceraria (200mg/kg) with Imipramine gave a highly significant result (p<0.001) in reduction of immobility duration and the effect of high dose (400mg/kg) with imipramine (15mg/kg) did not decrease the duration of immobility period in both animal models at end of the study. In this work the dose of 400mg/kg afforded more protection than the imipramine.Conclusions: The results obtained from this study was indicate that the antidepressant activity of L. siseraria.

Antidepressant activity of aqueous extract of Momordica charantia leaves

Background: Depression is a common debilitating illness contributing to increase in morbidity and mortality worldwide. 20% of all depressed patients are refractory to treatment with available antidepressants at adequate doses. Momordica charantia commonly known as Karela is widely used in Indian cuisine. This study was carried out to evaluate its lesser known Antidepressant activity. The objective of this study is to evaluate the Antidepressant activity of Aqueous extract of Momordica charantia leaves.Methods: This study was done in Department of Pharmacology, JNMC, AMU. Tail Suspension test and 5-Hydroxytrytophan induced Head Potentiation was evaluated in Swiss Albino mice. Forced swim test, Learned Helplessness test and Spontaneous motor activity was noted in Albino Wistar rats respectively at doses of AEMC (Aqueous extract of Momordica charantia leaves) 100mg/kg, 200mg/kg and 300mg/kg.Results: AEMC at all three doses 100mg/kg, 200mg/kg and 300mg/kg exhibited antidepressant activity by significantly decreasing the immobility time in Tail Suspension test and except 100mg/kg. In forced swim test psychostimulant activity of AEMC was ruled out in Spontaneous motor activity. Number of Escape failures was decreased in Learned Helplessness test at doses of AEMC 200mg/kg and 300 mg/kg. Increase in Head twitches was seen only with AEMC 300mg/kg in 5-Hydroxytrytophan induced Head Potentiation in mice.Conclusions: Aqueous Extract of Momordica Charantia leaves exhibits Antidepressant activity in animal models of Depression.

The effect of docosahexaenoic acid (DHA) supplementation on experimental depression in mice

Background: Depressive disorder is a prevalent psychiatric disorder, which affects 21% of the world population. Many drugs which are available as effective antidepressants produce various side effects like sedation weight gain postural hypotension etc., so there is need to develop novel compounds with minimized side effects. Hence this study was aimed to investigate the antidepressant activity of DHA, an omega-3 polyunsaturated fatty acid in albino mice.Methods: Animals were divided into four groups, consisting six mice in each group. Out of these, group I served as control (2% gum acacia), group II and III received test drug in two different doses 200mg/kg and 300mg/kg respectively and group IV received fluoxetine (20mg/kg) as standard drug. To determine the antidepressant-like activity, we used forced swim test and tail suspension test in mice. These methods are based on the observation that a mouse show alternating agitation and immobility; the immobility is indicative of a state of depression.Results: DHA produced significant antidepressant effect at all the doses, as indicated by reduction in immobility times as compared to control in both FST and TST. (P?0.05) The efficacy of DHA at dose of 300 mg/kg was comparable with that of fluoxetine. DHA at 200mg/kg dose showed significantly less antidepressant activity compared to fluoxetine. (P?0.05).Conclusions: The result specifies that compared to two doses of DHA (200mg/kg and 300mg/kg), higher dose of DHA found as an effective dose for treating depression produced due to stress.

Measurement and analysis of the behavioral changes of Rncat congenital cataract mice / 中国比较医学杂志

Objective To measure and analyze the behavioral changes of Rncat congenital cataract mice. Methods Normal BALB/c mice and KM mice were used as control group,and inbred and random mated Rncat congenital cataract mice were used as experimental group. Behavioral tests, including the open field test, coat-hanger test, forced swimming test,and tail suspension test,were conducted on the mice. Results Compared with the inbred Rncat congenital cataract mice,the residence time in the open field test,the immobility time in the forced swimming test and tail suspension test of the BALB/c mice, randomly-mated Rncat congenital cataract mice and KM mice were significantly different. Conclusions There are certain differences in behavioral performance between the Rncat congenital cataract mice and the other mice. Our findings may provide a useful reference for future researchers.

The effect of periodic dynamic mechanical load with different intensity on microgravity-induced osteoporosis / 医用生物力学

Objective To investigate the role and influence of physiological loading and overloading on microgravity-induced osteoporosis,so as to find a reliable way to prevent or treat related-orthopedic disorders in astronauts induced by long-time space activity.Metbods The microgravity environment in space was simulated by tail-suspension experiment,then the osteoporosis models of mice were built.A total of 32 C57BL/6J mice were randomly and evenly separated into four groups:normal group (normal),tail-suspension group (TS),physiological loading group (loading) and overloading group (overloading).Periodic dynamic mechanical load was applied on the left tibia in loading group and overloading group during tail-suspension test.After four weeks,tibial mechanical properties,micro-parameters of bone trabecular,biochemical indices and osteogenesis-related gene expression in each group were compared and analyzed.Results A great loss of tibial cancellous bone,significantly lower tibial biomechanical expression,serious damage of microstructure and weaker osteogenic activity were found in tail-suspended mice as compared with those of normal group.Physiological loading could clearly improve mechanical properties of bones,microstructure of bone trabecular,osteogenic activity and relative gene expression (P ＜ 0.05).Overloading could also improve the condition of microgravity-induced osteoporosis,but the effect was not obvious (P ＞ 0.05).Conclusions Tail-suspension can successfully simulate microgravity environment and duplicate osteoporosis model.Physiological loading can effectively prevent the emergence and development of microgravity-induced osteoporosis,while overloading can also counter microgravity-induced osteoporosis,but the results have no significant differences.

The effect of periodic dynamic mechanical load with different intensity on microgravity-induced osteoporosis / 医用生物力学

Objective To investigate the role and influence of physiological loading and overloading on microgravity-induced osteoporosis, so as to find a reliable way to prevent or treat related-orthopedic disorders in astronauts induced by long-time space activity. Methods The microgravity environment in space was simulated by tail-suspension experiment, then the osteoporosis models of mice were built. A total of 32 C57BL/6J mice were randomly and evenly separated into four groups: normal group (normal), tail-suspension group (TS), physiological loading group (loading) and overloading group (overloading). Periodic dynamic mechanical load was applied on the left tibia in loading group and overloading group during tail-suspension test. After four weeks, tibial mechanical properties, micro-parameters of bone trabecular, biochemical indices and osteogenesis-related gene expression in each group were compared and analyzed. Results A great loss of tibial cancellous bone, significantly lower tibial biomechanical expression, serious damage of microstructure and weaker osteogenic activity were found in tail-suspended mice as compared with those of normal group. Physiological loading could clearly improve mechanical properties of bones, microstructure of bone trabecular, osteogenic activity and relative gene expression (P＜0.05). Overloading could also improve the condition of microgravity-induced osteoporosis, but the effect was not obvious (P＞0.05). Conclusions Tail-suspension can successfully simulate microgravity environment and duplicate osteoporosis model. Physiological loading can effectively prevent the emergence and development of microgravity-induced osteoporosis, while overloading can also counter microgravity-induced osteoporosis, but the results have no significant differences.

The effect of periodic dynamic mechanical load with different intensity on microgravity-induced osteoporosis / 医用生物力学

Objective To investigate the role and influence of physiological loading and overloading on microgravity-induced osteoporosis,so as to find a reliable way to prevent or treat related-orthopedic disorders in astronauts induced by long-time space activity.Metbods The microgravity environment in space was simulated by tail-suspension experiment,then the osteoporosis models of mice were built.A total of 32 C57BL/6J mice were randomly and evenly separated into four groups:normal group (normal),tail-suspension group (TS),physiological loading group (loading) and overloading group (overloading).Periodic dynamic mechanical load was applied on the left tibia in loading group and overloading group during tail-suspension test.After four weeks,tibial mechanical properties,micro-parameters of bone trabecular,biochemical indices and osteogenesis-related gene expression in each group were compared and analyzed.Results A great loss of tibial cancellous bone,significantly lower tibial biomechanical expression,serious damage of microstructure and weaker osteogenic activity were found in tail-suspended mice as compared with those of normal group.Physiological loading could clearly improve mechanical properties of bones,microstructure of bone trabecular,osteogenic activity and relative gene expression (P ＜ 0.05).Overloading could also improve the condition of microgravity-induced osteoporosis,but the effect was not obvious (P ＞ 0.05).Conclusions Tail-suspension can successfully simulate microgravity environment and duplicate osteoporosis model.Physiological loading can effectively prevent the emergence and development of microgravity-induced osteoporosis,while overloading can also counter microgravity-induced osteoporosis,but the results have no significant differences.

The effect of periodic dynamic mechanical load with different intensity on microgravity-induced osteoporosis / 医用生物力学

Objective To investigate the role and influence of physiological loading and overloading on microgravity-induced osteoporosis,so as to find a reliable way to prevent or treat related-orthopedic disorders in astronauts induced by long-time space activity.Metbods The microgravity environment in space was simulated by tail-suspension experiment,then the osteoporosis models of mice were built.A total of 32 C57BL/6J mice were randomly and evenly separated into four groups:normal group (normal),tail-suspension group (TS),physiological loading group (loading) and overloading group (overloading).Periodic dynamic mechanical load was applied on the left tibia in loading group and overloading group during tail-suspension test.After four weeks,tibial mechanical properties,micro-parameters of bone trabecular,biochemical indices and osteogenesis-related gene expression in each group were compared and analyzed.Results A great loss of tibial cancellous bone,significantly lower tibial biomechanical expression,serious damage of microstructure and weaker osteogenic activity were found in tail-suspended mice as compared with those of normal group.Physiological loading could clearly improve mechanical properties of bones,microstructure of bone trabecular,osteogenic activity and relative gene expression (P ＜ 0.05).Overloading could also improve the condition of microgravity-induced osteoporosis,but the effect was not obvious (P ＞ 0.05).Conclusions Tail-suspension can successfully simulate microgravity environment and duplicate osteoporosis model.Physiological loading can effectively prevent the emergence and development of microgravity-induced osteoporosis,while overloading can also counter microgravity-induced osteoporosis,but the results have no significant differences.

Effect of simvastatin on bone mass recovery in rats with reloading after tail-suspension / 中国比较医学杂志

Objective To observe the changes of bone mass in reloaded rats after tail-suspension,and the effect and mechanism of simvastatin on this process.Methods Twenty-four 5-month old rats were divided into 4 groups of 6 animals in each group: Control (CL) group without tail-suspension,unloaded (UL) group with tail-suspension for 6 weeks,other 12 rats received tail-suspension for 3 weeks,then reloaded for subsequent 3 weeks (UL+RL) or combined with simvastatin treatment (UL+RL+SIM) at a dose of 10 mg/kg/d.All rats were sacrificed 6 weeks later,and the left femur was used for examination of bone mineral density,left tibia was used for bone histomorphometry analysis,the right femur and tibia were harvested for biomechanical test,and expression levels of type I collagen by real-time PCR and Western blot,respectively.Results 1.BMD of the CL group was significantly higher than those of the other three groups (P<0.05),and was markedly lower than those in the UL+RL and UL+RL+SIM groups (P<0.05).2.The bone histomorphometry showed that BV/TV in the CL group was significantly higher than those in the other 3 groups,and the UL+RL and UL+RL+SIM groups showed a significantly higher BV/TV than that of UL group (P<0.05).The Tb.Th was significantly higher in the CL group than in the UL group.The Tb.Sp in the CL group was significantly lower than those in the other 3 groups (P<0.05).The UL+RL and UL+RL+SIM groups showed significantly lower Tb.Sp than that of the UL group (P<0.05).3.Biomechanical test showed that the maximal load and elastic modulus in the CL groups were significantly higher than those of the other three groups (P<0.05).4.Real-time PCR showed that no significant difference in the mRNA expression level of Col I was found between any two groups.5.Western blot showed that the IOD of Col I is significantly lower than that in the CL group.Conslusions Bone loss,destruction of trabecular bone micro-architecture and biomechanical properties and reduction of type 1 collagen are present in tail-suspension treated rats,which are partially restored after reloading,and this recovery process is not enhanced by simvastatin treatment.

Effect of maternal separation stress on behavior of neonatal rd mice / 中国比较医学杂志

Objective To evaluate the effect of maternal separation stress on the behavior of neonatal rd mice.Methods Neonatal rd mice were divided into maternal separation (MS) group (n=9) and control group (n=9).MS-stress was induced in the MS group by 4-hour-separation per day for 28 days.Open field test,elevated plus maze test,forced swim test and tail suspension test were used to evaluate the anxiety-like and depression-like behavior of the neonatal rd mice.Results The stay time and distance travelled of MS group in the central zone were 0.88％ and 28.17±5.65 cm,respectively,significantly shorter than that of the control group (2.61％,109.9±9.79 cm.P =0.04,P =0.001).Compared with the control group,the stay time in open arms of the MS group was significantly decreased (P<0.01),while the immobility time in forced swim test and tail suspension test of the MS group were 126.5±10.22 s and 21.56±6.83 s,significantly longer than that of the control group (77.75±16.83 s,P =0.02,7.37±3.22 s,P =0.03).Conclutions The 28-day maternal separation stress can significantly increase the anxiety-like and depression-like behavior in neonatal rd mice.

Atividade antidepressiva do extrato etanólico da Kielmeyera Rubriflora Cambes (Pau Santo) em camundongos / Actividad antidepressiva del extracto etanolico de la Kielmeyera Rubriflora Cambes (Pau Santo) en ratones / Antidepressant activity of Kielmeyera Rubriflora Cambes (Pau Santo) ethanolic extract on mice

Introdução: a Kielmeyera rubriflora Cambess, pertencente à família Clusiacea, é uma planta nativa do Vale do Jequitinhonha em Minas Gerais no Brasil, onde é utilizada na medicina caseira. É conhecida como Pau Santo, Rosa do Campo, Flor de Santa Rita ou Rosa do Cerrado. Entretanto, até o momento não existem dados disponíveis na literatura no que diz respeito a estudos farmacológicos desta espécie. A Kielmeyera coriácea também é uma planta nativa da região e já existem estudos revelando sua ação antidepressiva. Objetivo: avaliar a ação antidepressiva do extrato etanólico das partes aéreas da K. rubriflora em camundongos. Método: o extrato etanólico das partes aéreas foi administrado por v.o. nas doses de 100 mg/kg, 250 mg/kg e 500 mg/kg em camundongos albinos, suíços, machos, com idade entre 9 e 13 semanas, com peso entre 29 e 43 g. Para a investigação dos efeitos antidepressivos foram utilizados os testes de triagem farmacológica comportamental (administração aguda), nado forçado (administração crônica) e suspensão da cauda (administração crônica). Resultados: na triagem farmacológica comportamental, foram detectados efeitos de depressão do sistema nervoso central pela dose de 100 mg/kg e de estímulo do sistema nervoso central nas doses de 250 e 500 mg/kg. No teste da suspensão da cauda houve diminuição dose-dependente, porém não significativa do tempo de imobilidade. No teste de nado forçado houve diminuição significativa do tempo de imobilidade em todas as doses investigadas sugerindo atividade antidepressiva, principalmente na dose de 100 mg/kg. Conclusão: os dados encontrados sugerem ação antidepressiva do extrato etanólico das partes aéreas da K. rubriflora(AU)

Introducción: la Kielmeyera rubriflora Cambess, perteneciente a la familia Clusiaceae, es una planta nativa del Valle de Jequitinhonha, en Minas Gerais en Brasil, donde se utiliza en la medicina popular. Se le conoce como Pau Santo, Rosa do Campo, Flor de Santa Rita o Rosa do Cerrado. Sin embargo, hasta ahora no hay datos disponibles en la literatura con respecto a los estudios farmacológicos de esta especie. La Kielmeyera coriacea es también una planta nativa de la región y ya hay estudios que revelan su acción antidepresiva. Objetivo: evaluar la acción antidepresiva del extracto crudo de las partes aéreas de la K. rubriflora en ratones. Método: el extracto crudo de las partes aéreas se administró v.o. en dosis de 100 mg/kg, 250 mg/kg y 500 mg/kg en ratones albinos, suizos, machos, con edades comprendidas entre 9 y 13 semanas, con un peso entre 29 y 43 g. Para la investigación de los efectos antidepressivos se utilizaron pruebas de screening farmacológico de comportamiento (administración aguda), nado forzado (administración crónica) y suspensión de la cola (administración crónica). Resultados: en el screening farmacológico de comportamiento se detectaron efectos de depresión del sistema nervoso central por la dosis de 100 mg/kg y estimulación del sistema nervoso central con las dosis de 250 y 500 mg/kg. En el ensayo de suspensión de cola hubo una disminución dependiente de la dosis, pero no significativa en el tiempo de inmovilidad. En la prueba de nado forzado hubo una disminución significativa en el tiempo de inmovilidad en todas las dosis investigadas, sugiriendo actividad antidepresiva, en particular a una dosis de 100 mg/kg. Conclusión: los resultados sugieren la acción antidepresiva del extracto crudo de las partes aéreas de la K. rubriflora(AU)

Introduction: The Kielmeyera rubriflora Cambess, belonging to the Clusiaceae family, is a native to the Vale do Jequitinhonha in Minas Gerais in Brazil, where it is used in folk medicine. It is popularly known as Pau Santo, Rosa do Campo, Flor de Santa Rita and Rosa do Cerrado. However, so far there are no data available in the literature on pharmacological studies regarding this species. The Kielmeyera coriácea is also a native plant in the region and there are already studies revealing its antidepressant action. Objective: To evaluate the antidepressant action of the crude extract fron the aerial parts of K. rubriflora in mice. Method: The crude extract from the aerial parts was administered v.o. at doses of 100 mg/kg, 250 mg/kg and 500 mg/kg in albino Swiss, male mice, between 9 and 13 weeks of age, weighing between 29 and 43 g. In order to the investigation of antidepressant effects, the behavioral pharmacological screening (acute administration), forced swimming (chronic administration) and tail suspension (chronic administration) tests were performed. Results: In the behavioral pharmacological screening were detected central nervous system depression effects with the dose of 100mg/kg and central nervous system stimulation with the doses of 250 and 500 mg/kg. In the tail suspension test, a dose-dependent, but not significant, decrease in the immobility time was observed. In the forced swimming test a significantly lower immobility time was observed at all doses investigated, suggesting an antidepressant activity, especially at a dose of 100 mg/kg. Conclusion: The results suggests an antidepressant action of the crude extract fron the aerial parts of K. rubriflora(AU)

Evaluation of the antidepressant activity of Moringa oleifera alone and in combination with fluoxetine.

Background: The prevalence of mental depression has increased in recent years, and has become a serious health problem in most countries of the world, including India. Due to the high cost of antidepressant synthetic drugs and their accompanying side effects, the discovery of safer antidepressant herbal remedies is on the rise. Moringa oleifera (MO) (drumstick) has been used in traditional folk medicine, and in Ayurveda, it is considered as a valuable remedy for treating nervous system disorders as well as memory enhancing agent. Objective: The present study was designed to evaluate the acute and chronic behavioral and antidepressant effects of alcoholic extracts of MO leaves in standardized mouse models of depression. Materials and Methods: Alcoholic extracts of MO (MOE) leaves were prepared, and phytoconstituents were determined using appropriate chemical analytical methods. Following preliminary dose‑finding toxicity studies, the biological activity of MOE was tested in Swiss albino mice. Animals were divided into six groups: Groups 1 and 2 served as vehicle control and fluoxetine (20 mg/kg) standard control, respectively. Groups 3 and 4 served as treatment groups and were orally administered ethanolic MOE at doses of 100 mg/kg and 200 mg/kg, respectively. Groups 5 and 6, respectively, received combination doses of MOE 100 mg/kg + 10 mg fluoxetine, and MOE 200 mg/kg + 10 mg/kg fluoxetine. Following acute and 14 days chronic treatments, all animals were tested using behavioral models of depression, such as forced swim test (FST), tail suspension test (TST), and locomotor activity test (LAT). Results: Significant changes in all tested activities (FST, TST, LAT) of chronically dosed mice were observed, especially in animals given simultaneously combined doses of 200 mg/kg/day MOE + 10 mg/kg/day fluoxetine for 14 days. The antidepressant effect of MOE may have been invoked through the noradrenergic‑serotonergic neurotransmission pathway, which is the hallmark of selective serotonin reuptake inhibitors (SSRI) class of drugs. Conclusion: The results obtained in this study suggest that combined administration of MOE with low doses of fluoxetine or other SSRI drugs seems to have promising potential.

To investigate the role of Memantine as anxiolytic in elevated plus maze test and as antidepressant in tail suspension test in Swiss albino mice.

Background: The magnitude of improvement seen with present conventional medicines for anxiety and depression remain disappointing thereby providing a scope for the study of newer drugs. In the literature, there is evidence demonstrating the modulation of N-methyl-D-aspartate (NMDA)receptors in anxiety and depression. The present study is undertaken to evaluate the antianxiety effect of memantine in elevated plus maze (EPZ) test and its antidepressant effect in tail suspension test (TST)in Swiss albino mice. Methods: Animals were divided into six groups (n=6). First group mice were given normal saline (10 ml/kg), second group were administered lorazepam (0.5 mg/kg), third group with memantine (3 mg/kg) and fourth group with memantine plus lorazepam, fi fth group was administered amitriptyline (10 mg/kg)and sixth group received memantine plus amitriptyline. All drugs were administered by intraperitoneal route daily for 7 consecutive days. Results were analyzed by one-way ANOVA followed by post-hoc Tukey’s test. Results: Memantine treated mice showed signifi cant increase (p<0.001)in time spent and number of entries in open arm and signifi cant decrease in time spent and number of entries in closed arm in EPZ when compared to control group. Duration of immobility was signifi cantly (p<0.001)reduced in animals treated with memantine when compared to the control group in TST. Conclusions: NMDA antagonist, memantine has showed signifi cant antianxiety effect in EPZ test and antidepressant effect in TST.

Antidepressant-like properties of Antiaris toxicaria aqueous extract.

Background: Depression is a global burden whose therapy is plagued with inconsistent effi cacy. Hence, the need for the discovery of newer therapies. Methods: In this study, Antiaris toxicaria extract (200, 400 and 800 mg/kg, p.o.), was evaluated for antidepressant activity using behavioral tests battery particularly the forced swim test (FST) and tail suspension test (TST). In order to investigate its mechanism of action, animals groups were pretreated with α-methyldopa (α-MD), para-chlorophenylalanine (PCPA), reserpine, D-serine and 5-hydroxytryptophan. Results: It increased the mobility periods and decreased immobility periods signifi cantly in both the FST and the TST when compared to the control group. But the TST showed more promising effect than the FST. Pre-treatment with α-MD reversed the antidepressant property of A. toxicaria aqueous extract as did PCPA, reserpine and reserpine combined with α-MD. The extract increased the number of head twitches produced by 5-hydroxytryptophan confi rming the involvement of serotonin in the antidepressant property and inhibited carbachol-induced contractions on the isolated rat uterus, which was non-competitively antagonized by propranolol. Treatment with D-serine produced no signifi cant increase in the immobility time produced by the extract at the doses studied. This excludes the involvement of N-methyl-d-aspartate in the possible mechanisms of action. Conclusion: A. toxicaria possesses antidepressant-like action in rodents.

Effects of vascular endothelial growth factor on bone loss of the proximal tibia in tail-suspended rats / 医用生物力学

Objective To investigate the effects of vascular endothelial growth factor (VEGF) on disused bone loss. Methods Tail-suspended (TS) rat models were established and evenly divided into TS+Saline group, TS+VEGF group, CON+Saline group and CON+VEGF group. During the experiment, VEGF or equivalent amount of saline was injected into the gastrocnemius muscle of the rats’ right tibia twice a week for each rat. After four weeks, the proximal tibia of the rats was scanned by micro-CT. The bone mineral density (BMD) of the trabecular bone and cortical bone, micro-structure parameters of the trabecular bone, such as bone volume per trabecular volume (BV/TV), tabecular number (Tb.N), trabecular spacing (Tb.Sp), structure model index (SMI), and cortical thickness were used as evaluation indices to study the influence of VEGF on bone loss in the proximal tibia of tail-suspended rats. Results Compared with the control rats, in tail-suspended groups, the apparent BMD, BV/TV, Tb.N, SMI of trabecular bone and the cortical thickness all decreased significantly, while the Tb.Sp and SMI significantly increased, which showed that tail suspension would cause bone loss, while the injection of VEGF would alleviate the loss of trabecular bone in tail-suspended rats. Conclusions There might exist some relationship between the status of blood supply and bone remodeling process, and by improving the status of vascular system, the disused bone loss can be alleviated.