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OBJECTIVE To screen the effective anti-depressant part from Coreopsis tinctoria and study its mechanism. METHODS The anti-depressant effects of 30％，50％，70％ and 90％ ethanol elution fractions from 75％ ethanol extract of C. tinctoria（CCTE）were investigated by tail suspension test and forced swimming test. Mice head-drop test ，reserpine antagonistic test，yohimbine toxicity enhancement test and in vitro monoamine oxidase （MAO） inhibition test were used to explore the mechanism of the relationship between the effective parts and 5-hydroxytryptamine （5-HT） and norepinephrine （NE） nerves. RESULTS The 50％ and 70％CCTE could significantly shorten the accumulative immobility time in tail suspension test and forced swimming test （P＜0.05 or P＜0.01），increase the number of head-shaking times （P＜0.01），reverse the eyelid ptosis ， hypothermia and immobility caused by hematopin （P＜0.05 or P＜0.01），and increase the number of dead mice caused by yohimbine toxicity （P＜0.01）. IC 50 of okanin （CCT-6），isookanin（CCT-7）and taxifolin （CCT-8）against MAO were 8.71，37.89 and 67.07 µmol/L，respectively. CONCLUSIONS The 50％ and 70％CCTE are the effective anti-depressant parts of C. tinctoria . Its anti-depressant effect may be related to the reinforcement of 5-HT and the activation of NE nerves. The inhibition of CCT- 6， CCT-7 and CCT- 8 against MAO may be one of the anti-depressant mechanism of C. tinctoria .
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Objective: To develop and validate the RP-HPLC method and in vitro dissolution study for escitalopram as antidepressant drug and their formulation. Methods: The chromatographic separation was done by using a C-18, 150 mm column and a mobile phase consisting of phosphate buffer (40%) and acetonitrile HPLC grade (60%). Detection was carried out at 211 nm with a flow rate of 1 ml/min with an injection of 20 μl. The method was validated with different parameters such as linearity, precision, accuracy, robustness, and limit of detection (LOD), the limit of quantification (LOQ) according to ICH guidelines. Results: The linear calibration curve was obtained in the concentration range of 0-50 μg/ml and gave an average correlation factor 0.992. The retention time was observed at 2.96 min. The Minimum concentration level at which the analyte can be reliably detected (LOD) and quantified (LOQ) were found to be 0.03 and 0.09 µg/ml, respectively. The relative standard deviation of intra and the inter-day assay was found to be less than 2. The dissolution studies show moderate dissolution (23.4%) after 45 min, but it reaches a plateau after approximately 25 min. Conclusion: This method was found to be simple, rapid and economic with less run time. The validated parameters manifest the method is reliable, linear, accurate and precise as well as robust with minor variations in chromatographic parameters. Therefore, the developed method can be applied for both routine analysis and quality control assay and it could be a very powerful tool to investigate the stability of escitalopram.
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Citalopram is an antidepressant used for treating major depressive disorder. In the current work Citalopram HBr is formulated as mouth dissolving film with enhanced drug dissolution. The Central Composite Design (CCD), employed to examine the effects of amount of HPMC E50 (A), amount of maltodextrin (B) and amount of glycerol (C) on response variables tensile strength, disintegration time and cumulative % drug release. 27 formulations prepared according to CCD and evaluated for physicochemical parameters and in vitro dissolution studies. Citalopram HBr mouth dissolving films formulated by employing solvent-casting method using HPMC E50, maltodextrin and glycerol, optimized for the effective dosage of superdisintegrants. The formulation CF21 with maximum tensile strength of 67.21±1.31 gm, least disintegration time of 9±1.60 sec and highest drug release of 98.41±1.81% is chosen optimal formulation with maximum content uniformity and folding endurance. It is evident from the above results that the developed formulation can be an innovative dosage form to improve the drug delivery, quick onset of action as well as improve patient compliance in the effective management of depression.
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Background: To evaluate antidepressant activity of ethanolic extract of Trigonella foenum in animal models.Methods: A total of 60 healthy male Wistar albino rats weighing 220-250 grams were used and they were divided into 10 groups of 6 rats in each. First five groups (1st -5th) were evaluated by Forced Swim Test (FST) and remaining by Tail Suspension Test (TST). 1st group (control) received normal saline 10 mg/kg, 2nd group (standard) Imipramine 10 mg/kg and 3rd, 4th and 5th groups (test) respectively received Trigonella foenum leaf ethanolic extract [TFEE] in different doses 100 mg, 200 mg, and 400 mg/kg per orally for 14 days. They were evaluated for antidepressant activity using FST after 60 minutes of drug administration on 14th day. Similarly, remaining five groups (6th to 10th) received the same drugs and evaluated using TST after 60 minutes of drug administration. Duration of immobility was noted for six minutes for each rat.Results: One way ANOVA and Tukey Krammer test were used for statistical analysis. The immobility periods were expressed in mean±SD. The immobility period in FST were 207.16±28.7, 50.08±2.9, 46.14±1.2, 40.5±3.4 and 40.0±3.6 seconds respectively for control, standard and three test groups of TFEE (100/200/400 mg/kg). Similarly, immobility periods of 163.11±31.9, 125.03±11.2, 138.81±16.44, 138.16±12.65, 127.58±4.3 seconds were noted for TST for remaining six groups. It was found that TFEE possess statistically significant (p<0.05) antidepressant activity, as evidenced by decrease in the immobility time in both the tests when compared to control group.Conclusions: Present study results demonstrated that TFEE possess antidepressant property in experimental models of depression.
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OBJECTIVE： To study the anti-depressive effects of Wenyang jieyu granules and its possible mechanism. METHODS： A total of 60 rats with similar behavior and body weight were randomly divided into blank control group （distilled water）， model group （distilled water）， fluoxetine positive control group （2.10 mg/kg） and Wenyang jieyu granules low-dose， medium-dose and high-dose groups （1.89， 3.78， 7.56 g/kg）， with 10 rats in each group. They were given relevant medicine intragastrically， once a day， for consecutive 28 d. Except for blank control group， other groups were given chronic unpredictable mild stress combined with feeding alone to establish depression model. On the 0， 7th， 14th， 21st and 28th day of administration， the changes of body weight were measured. The sucrose reference test and open-field test were adopted to determined the rate of sucrose reference， total distance and four corner distance within 4 min. 1 h after last administration， forced swimming test was used to measure struggling time and floating time within 4 min. The contents of 5-hydroxytryptamine （5-HT） and dopamine （DA） in serum were determined by HPLC. RESULTS： Compared with blank control group， body weight （7th， 14th， 21st and 28th day of administration） and the rate of sucrose reference （14th， 21st and 28th day of administration） were decreased significantly （P＜0.05 or P＜0.01）； total distance and four corner distance within 4 min （21st and 28th day of administration） were decreased significantly； struggling time within 4 min was shortened significantly and floating time within 4 min was prolonged significantly （P＜0.01）； serum contents of 5-HT and DA were decreased significantly （P＜0.01）. Compared with model group， body weight （28th day of administration in low-dose group， 21st and 28th day of administration in medium-dose group and high-dose group） and the rate of sucrose reference （28th day of administration） were increased significantly in Wenyang jieyu granules groups （P＜0.05 or P＜0.01）； total distance and four corner distance within 4 min （21st and 28th day of administration） were increased significantly （P＜0.01）； struggling time within 4 min was prolonged significantly and floating time within 4 min was shortened significantly （P＜0.01）. Serum contents of 5-HT and DA were increased significantly （P＜0.05 or P＜0.01）. Compared with fluoxetine positive control group， there was no statistical significance in above indexes among Wenyang jieyu granules groups （P＞0.05）. CONCLUSIONS： Wenyang jieyu granule has obvious anti-depression effect on depression model rats， which is similar to fluoxetine， and its mechanism may be related to the down-regulation of serum contents of 5-HT and DA.
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The phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway is one of the important signaling pathways for regulating cell survival, differentiation and apoptosis in vivo, which plays an important role in the occurrence of cancer, diabetes, nervous system diseases and the mechanisms of related drugs. In recent years, attention has been paid to the role of PI3K/Akt signaling pathway in the study of depression and the mechanism of antidepressant traditional Chinese medicine. This article reviews the relationship between key targets of PI3K/Akt signaling pathway and depression, the role of PI3K/Akt signaling pathway in depression and PI3K/Akt signaling pathway in the study of mechanism of antidepressant traditional Chinese medicine, which provides a reference for the treatment of depression and the discovery of antidepressant drugs.
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Aim To establish a postpartum depression animal model,assess the abnormal maternal behaviors of depressive dams,and observe the rapid antidepres-sant effects of the Yuejuganmaidazaotang (YG)on the PPD model.Methods Thirty-two female Balb /c were randomly assigned to two groups,the control group (Control,con)and the pre-pregnancy stressed group (Vehicle,veh),and vehicle was subjected to 3 weeks chronic restraint stress.After the last stressor,the pre-pregnancy stressed group was housed with a male.Af-ter about 4 weeks later,the mice gave birth to pups. Then at 3 weeks postpartum,we tested the maternal depressive-like behaviors,including sucrose preference test,forced swimming test and novelty suppressed feeding test.Both YG and Ketamine were single ad-ministered 24 hours before behavior test,with single saline for control group and PPD model group.Results After 3 weeks postpartum,the vehicle mice showed depression-like behaviors.Reduced preference in drinking sucrose solution was found in SPT (P <0.01 ).Immobility in FST was significantly increased in vehicle groups (P <0.01 ).In NSFT,the vehicle group displayed a significantly increased latency and reduced unit of food intake compared with control group(P <0.01,P <0.01 ).Acute YG improved per-formance in the SPT(P <0.01),FST (P <0.01)and NSF (P <0.01,P <0.01),which was similar to ket-amine.Conclusions Chronic pre-pregnancy stress can induce dams into postpartum depression.Acute YG exert fast antidepressant effect on this PPD model simi-lar to ketamine.
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Background: Abelmoschus moschatus is an aromatic and medicinal plant, used as traditional medicine in the Thirunelveli district and distributed in many parts of Asia, including India. The present study was aimed to evaluate central nervous system (CNS) activities of ethanolic seed extract of A. moschatus (AEAM). Methods: Oral administration of AEAM at doses of 200 and 400 mg/kg on various behavioral models forced swim, tail suspension, light-dark box, hole-board, elevated-plus-maze, locomotor, strychnine, maximal electroshock induced seizure, pentylenetetrazole (PTZ), rotarod, climbing an inclined screen models were utilized. Results: In the open field test, AEAM (200 and 400 mg/kg) increased the numbers of rearing. However, the number of central motor and ambulation were reduced. The number of entries and the time spent in the open arm were increased, whereas the number of locomotion was decreased (p<0.001) in elevated-plus-maze and actophotometer test, respectively. AEAM (200 and 400 mg/kg) protected the mice against the PTZ and strychnine-induced convulsions; it causes significant dose-dependent increase in latency of convulsion. Treatment with AEAM reduced the duration of the tonic hind limb extension, increased the hypnotics time and decreased motor co-ordination of experimental animals. Conclusion: This study concludes A. moschatus is an alternative source for CNS drug development.
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Background: Depression is a common serious psychiatric disorder and the available anti-depressant treatments are associated with many unwanted side-effects. Thus, various herbal products have been tried. The advantages of herbal treatments would include its complementary nature to the conventional treatment, thus making the latter a safer and cheaper option for depressive disorders. The objective of the present study was to evaluate the anti-depressant activity of lemon grass (Cymbopogon citratus) in albino mice and compare it with Imipramine. Methods: A total of 60 Swiss albino mice weighing around 20-40 g of either sex were divided into 10 groups (n=6). They were orally administered with tween 80, as a control, 20 mg/kg imipramine (standard), 5 mg/kg and 10 mg/kg C. citratus (test drugs), and combination of imipramine (10 mg/kg) and C. citratus (10 mg/kg). Duration of immobility was observed for last 4 mins of total 6 mins period in groups 1-5 for forced swimming test (porsolt test) and groups 6-10 for tail suspension test each on 1st, 8th and 15th day and recorded as mean±standard error of the mean. Results were analyzed by one-way analysis of variance, followed by Tukey’s post-hoc test. Results: Lemon grass at the above doses significantly reduced the immobility time in both the tests compared with the control (<0.05). The reduction in the duration of immobility at the dose of 10 mg/kg was comparable to imipramine. Conclusions: The essential oil of lemon grass (C. citratus) has significant anti-depressant activity comparable to imipramine.
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Cedrus deodara (Pinaceae) has been used traditionally in Ayurveda for the treatment of central nervous system disorders. 3,4-bis(3,4-dimethoxyphenyl)furan-2,5-dione (BDFD) was isolated from heart wood of Cedrus deodara and was shown to have antiepileptic and anxiolytic activity. Thus, the present study was aimed to explore its anti-depressant effect and to correlate the effect with serotonin and nor adrenaline levels of brain. Albino mice were used as experimental animal. Animals were divided in to three groups; vehicle control, imipramine (30 mg/kg i.p.), BDFD (100 mg/kg i.p.). Tail suspension test (TST) and forced swim test (FST) was performed to evaluate antidepressant effect of BDFD. BDFD (100 mg/kg, i.p.) showed a significant decrease in immobility time when subjected to FST whereas immobility time was not significantly altered in TST. BDFD treatment increased serotonin and noradrenaline levels in the brain which is indicative of BDFD having possible atypical antidepressant action.
Subject(s)
Animals , Mice , Brain , Cedrus , Central Nervous System Diseases , Epinephrine , Heart , Hindlimb Suspension , Imipramine , Norepinephrine , Rodentia , Serotonin , WoodABSTRACT
In the present study, the anti-depressant like effect of methyl gallate (MG) isolated from the stem bark of Acer barbinerve was examined in ICR mice. Body weight (BDW) and blood glucose (BDG) levels significantly decreased in the repeated restraint stress (RRS) group (2 h/day for 14 days) compared to the no stress (NS) group. To examine the effect of MG on RS-induced BDW loss and hypoglycemia, MG (10 mg/kg) and the anti-depressant fluoxetine (10 mg/kg) were administered daily for 14 days. Orally administered MG and fluoxetine significantly attenuated the RS-induced BDW loss and hypoglycemia. Interestingly, MG administered mice showed increased BDG levels in the normal and glucose feeding condition. Chronic RS-subjected mice showed immobilized and depressed behaviors. The effect of MG on the depressed behaviors was evaluated using the tail-suspension test (TST) and the forced swimming test (FST). In both tests, RS-induced immobilized behaviors were significantly reversed in MG and fluoxetine administered groups. Taken together, MG significantly attenuated the RS-induced BDW loss, hypoglycemia, and depressed behaviors. Considering that decreased BDG levels (hypoglycemia) can cause depression, MG may exert its anti-depressant like effect by preventing hypoglycemia. Our results suggest that MG isolated from A. barbinerve can exert anti-depressant like effect, and could be used as a new and natural anti-depressant therapy.
Subject(s)
Animals , Mice , Acer , Blood Glucose , Body Weight , Depression , Fluoxetine , Gallic Acid , Glucose , Hypoglycemia , Mice, Inbred ICR , Physical ExertionABSTRACT
N-Cyclohexyl-3-methoxyquinoxalin-2-carboxamide (QCM-13), a novel 5-HT3 antagonist identified from a series of compounds with higher pA2 (7.6) and good log P (2.91) value was screened in rodent models of depression such as forced swim test (FST), tail suspension test (TST), interaction studies with standard anti-depressants and confirmatory studies such as reversal of parthenolide induced depression and reserpine induced hypothermia. In FST (2 and 4 mg/kg) and TST (2 and 4 mg/kg), QCM-13 significantly reduced the duration of immobility in mice without affecting the base line locomotion. QCM-13 (2 and 4 mg/kg) was also found to have significant interaction with standard anti-depressants (fluoxetine and bupropion in FST and TST respectively). Further, reversal of parthenolide induced depression in mice and reserpine induced hypothermia in rat models indicate the serotonergic influence of QCM-13 for anti-depressant potential.
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The serotonin transporter (SERT) is the target site for serotonin reuptake inhibitors, which are the most widely used agents for treating various psychiatric diseases including depression. The SERT is a member of a large family of homologous integral membrane proteins. This transporter takes up 5-HT in a process that is coupled to the transmembrane movement of Na+, Cl-, and K+. The SERT may operate in at least two modes, an alternating access carrier or a channel. The function of SERT is acutely regulated by various protein kinases and phosphatases. The SERT gene is located on chromosome 17 and has several polymorphisms including 5-HTTLPR and intron 2 VNTR. Most studies involving the association between 5-HTTLPR and the response to SSRI in depression reported that l/l genotype showed better response and fewer side effects. But, it is too early to draw definite conclusion of the effects of 5-HTTLPR on anti-depressant treatment. Therefore, it is necessary to perform further studies reflecting various ethnicities and genetics of subjects as well as the environmental interactions. This review discusses recent advances in defining the structure, the action mechanism, the location, and the regulation of SERT. Furthermore, it discusses the function of SERT polymorphisms and its implications on the anti-depressant therapies.