Therapeutic effects of methimazole on 3,4-methylenedioxymethamphetamine-induced hyperthermia and serotonergic neurotoxicity.

3,4-methylenedioxymethamphetamine (MDMA) is a popular recreational drug, however over 200 studies demonstrate that acute (e.g. hyperthermia, rhabdomyolysis) and chronic (e.g. neurotoxicity) toxicity effects of MDMA were observed in different animals. Methimazole (MMI), an inhibitor of thyroid hormone synthesis, was found to significantly reduce the HSP72 expression of heat stress induced in fibroblasts. Hence, we attempted to understand the effects of MMI on MDMA induced changes in vivo. Male SD rats were randomly divided into four groups as follows:(a) water-saline (b) water-MDMA (c) MMI-saline and (d) MMI-MDMA group. In the temperature analysis test, MMI was found to alleviate MDMA-induced hyperthermia and increase the heat loss index (HLI), revealing its peripheral vasodilation effect. PET experiment suggested that MDMA induced elevated glucose uptake by skeletal muscles, which was resolved by MMI pretreatment. IHC staining (serotonin transporter, SERT) showed the evidence of neurotoxicity caused by MDMA (serotonin fiber loss), which was alleviated by MMI. Furthermore, the animal behaviour test (forced swimming test, FST) showed higher swimming time but lower immobility time in MMI-MDMA and MMI-saline groups. Taken together, treatment of MMI shows benefits such as lowered body temperature, alleviation of neurotoxicity and excited behaviour. However, further investigations should be conducted in the future to provide in-depth evidence for its clinical use.

Screening of anti-fatigue active ingredients of Eleutherococcus senticosus via spectrum-effect relationship based on factor analysis and LC-MS/MS.

ES contains compounds known to have significant anti-fatigue activity. In recent years, it has received extensive attention because it is efficient. However, its active ingredients on antifatigue effect are still unclear. This study attempts to establish the spectrum-effect relationship of ES antifatigue activity to screen the effective components. The results showed that the similarity of 15 ES fingerprints obtained by LC-MS/MS was 0.533-0.992, and the chemical structures of 22 common peaks were identified. The anti-fatigue activity of 15 batches of ES was characterized by forced swimming test of mice and quantified by CAFI, among which S4, S1 and S5 had better activity. 9 components (caffeic acid, 5-(4-O-ß-D-glucosylferoyl)-quinic acid, (±)13-HODE, isofraxidin, eleutheroside E, syringin, pinoresinol diglucoside or its isomer, 7,8-dihydrodehydrocarbinol alcohol-4-O-ß-D-glucoside, secoisolariciresinol-4-O-ß-D-glucoside) highly related to anti-fatigue activity may be the effective components of ES.

Involvement of the serotonergic system in the antidepressant-like effect of 1-(phenylselanyl)-2-(p-tolyl)indolizine in mice.

RATIONALE: Depression is a mental disorder that affects approximately 280 million people worldwide. In the search for new treatments for mood disorders, compounds containing selenium and indolizine derivatives show promising results. OBJECTIVES AND METHODS: To evaluate the antidepressant-like effect of 1-(phenylselanyl)-2-(p-tolyl)indolizine (MeSeI) (0.5-50 mg/kg, intragastric-i.g.) on the tail suspension test (TST) and the forced swim test (FST) in adult male Swiss mice and to elucidate the role of the serotonergic system in this effect through pharmacological and in silico approaches, as well to evaluate acute oral toxicity at a high dose (300 mg/kg). RESULTS: MeSeI administered 30 min before the FST and the TST reduced immobility time at doses from 1 mg/kg and at 50 mg/kg and increased the latency time for the first episode of immobility, demonstrating an antidepressant-like effect. In the open field test (OFT), MeSeI did not change the locomotor activity. The antidepressant-like effect of MeSeI (50 mg/kg, i.g.) was prevented by the pre-treatment with p-chlorophenylalanine (p-CPA), a selective tryptophan hydroxylase inhibitor (100 mg/kg, intraperitoneally-i.p. for 4 days), with ketanserin, a 5-HT2A/2C receptor antagonist (1 mg/kg, i.p.), and with GR113808, a 5-HT4 receptor antagonist (0.1 mg/kg, i.p.), but not with WAY100635, a selective 5-HT1A receptor antagonist (0.1 mg/kg, subcutaneous-s.c.) and ondansetron, a 5-HT3 receptor antagonist (1 mg/kg, i.p.). MeSeI showed a binding affinity with 5-HT2A, 5 -HT2C, and 5-HT4 receptors by molecular docking. MeSeI (300 mg/kg, i.g.) demonstrated low potential to cause acute toxicity in adult female Swiss mice. CONCLUSION: In summary, MeSeI exhibits an antidepressant-like effect mediated by the serotonergic system and could be considered for the development of new treatment strategies for depression.

Hydroalcoholic Extract of Rabbiteye Blueberry (Vaccinium ashei) Leaves Mitigates Unpredictable Chronic Mild Stress Model Inducing Depressive-Like Behavior in Rats.

Several studies reported that rabbiteye blueberry (Vaccinium ashei Reade) leaves present promising biological properties. To the best of our knowledge, no study investigated the possible application of their hydroalcoholic extract for treating mood disorders. Herein, we evaluated if the hydroalcoholic extract of rabbiteye blueberry (Vaccinium ashei Reade) leaves (HEV) promotes an antidepressant-like effect in rodents using chronic experimental approaches. The effect of repeated administration of HEV (50 mg/kg, p.o.) on the immobility time was assessed in the forced swimming test (FST) in an unpredictable chronic mild stress (UCMS) model. Repeated treatment with HEV reversed the depressive-like behavior induced by UCMS by reducing the immobility time. Besides, the exposure to HEV caused no changes in relative organ weights in rats submitted to UCMS. The results indicated that HEV administration presented antidepressant-like action devoid of toxic effects. Thus, it is possible to suggest its potential as a safe and accessible therapeutic tool in the management of depression and other related mood disorders.

In Vivo Antidepressant-Like Effect Assessment of Two Aloysia Species in Mice and LCMS Chemical Characterization of Ethanol Extract.

Medicinal plants belonging to the Verbenaceae family demonstrated antidepressant effects in preclinical studies. Depression is one of the largest contributors to the global health burden of all countries. Plants from the Aloysia genus are traditionally used for affective disorders, and some of them have proven anxiolytic and antidepressant activity. The aim of this work was to evaluate the antidepressant effect of the ethanolic extract of Aloysia gratissima var. gratissima (Agg) and Aloysia virgata var. platyphylla (Avp) in mice. A tail suspension test (TST) and forced swimming test (FST) were conducted after three doses in a period of 24 h and after 7 days of treatment. Imipramine was used as an antidepressant drug. The main results demonstrated that Agg extract reduced the immobility time in mice treated orally for 7 consecutive days when compared to the control group (reduced by about 77%, imipramine 70%). Animals treated with three doses of Avp in a 24-h period had reduced immobility time in the FST (60%), and after 7 days of treatment the reduction was greater (Avp 50, 100, and 200 about 85%; Avp 400, 96.5%; p < 0.0001, imipramine, 77%). LCMS analysis showed the presence of verbascoside, hoffmaniaketone, and hoffmaniaketone acetate in both, A. virgata var. platyphylla and A. gratissima var gratissima. The flavonoids nepetin and 6-hydroxyluteolin were also found in Agg. Both tested extracts demonstrated promising antidepressant-like activity in mice.

Kamikihito rescued depressive-like behaviors and hippocampus neurogenesis in chronic restraint stress rats.

Background and aim: Substantial evidence suggests the effectiveness of plant-based medicine in stress-related diseases. Kamikihito (KKT), a Japanese traditional herbal medicine (Kampo), has been used for anemia, insomnia, and anxiety. Recent studies revealed its ameliorating effect on cognitive and memory dysfunction in several animal models. We, therefore, determined whether daily supplementation of KKT has an antidepressant-like effect on the stress-induced behavioral and neurological changes in rats. Experimental procedure: The effect of KKT against the stress-induced changes in anxiety- and depressive-like behaviors and hippocampal neurogenesis were determined using a rat model of chronic restraint stress (CRS). KKT was orally administered daily at 300 or 1000 mg/kg during 21 consecutive days of CRS (6 h/day). The effect of CRS and KKT on physiological parameters, including body weight gain, food/water consumptions, plasma corticosterone (CORT) levels, and percentage of adrenal gland weight to body weight, were firstly measured. Anxiety- and depressive-like behaviors in rats were assessed in the open field test (OFT), sucrose preference test (SPT), and forced swimming test (FST). Hippocampal neurogenesis was determined by immunohistochemistry. Results and conclusion: CRS for 21 days caused a significant decrease in body weight gain and increase in plasma CORT levels and percentage of adrenal gland weight to body weight, which were rescued by KKT treatment. KKT also suppressed the CRS-induced anxiety- and depressive-like behaviors and impairment of hippocampal neurogenesis. These results suggest that daily treatment of KKT has a protective effect against physiological, neurological, and behavioral changes in a rat model of depression.

Ergogenic property of Morinda citrifolia L. leaf extract affects energy metabolism in obese Sprague Dawley rats.

Ergogenic property is the ability to enhance capacity for physical activities through efficient production of energy and is potentially beneficial in weight management for the obese. In this study, ergogenic property of Morinda citrifolia leaf's extract (MCL) was evaluated using AMP-activated protein kinase (AMPK) activity and high fat diet-induced obese rats. Findings from the study showed that MCL demonstrated ergogenic activity via enhancement of AMPK activity using L6 skeletal muscle cell line. Interestingly, the result also revealed that rats treated with the intermediate dosage of MCL experienced the lowest % weight gain. The rats fed the highest dose of 200 mg/kg BW MCL demonstrated the longest swimming time of approximately three times that of green tea and caffeine-fed rats. The highest dose fed rats were also found to have lower glucose and lactate levels, suggesting that energy metabolism was more effective in these rats. In addition, lactate dehydrogenase and creatinine kinase activities, the muscle injury indicators, were found to be the lowest in rats fed the highest MCL dose. The same effect was not seen in rats fed either caffeine or green tea, indicating that MCL treatment is may be protective of the rats' muscles. It was also shown that MCL consisted of various flavonoids with epicatechin, catechin, and quercetin that may be responsible for the effects measured. In conclusion, improvements were seen in rats fed MCL in terms of weight management, endurance capacity, energy metabolism, and muscle injury parameters. PRACTICAL APPLICATIONS: Results of the study revealed that Morinda citrifolia leaf has great potential to be used as functional ingredient in the development of designer food/drink as ergogenic aid for both obese and non-obese individuals. Morinda citrifolia leaf could help in the weight management of obese people and enhance endurance capacity and energy metabolism in active individuals.

Anxiolytic-like and antidepressant-like effects of ethanol extract of Terminalia chebula in mice.

Terminalia chebula (T.chebula) fruit is referred as "King of Medicines" in Tibet and is listed as a key plant in "Ayurvedic Materia Medica" due to its diverse pharmacological activity. The present study was aimed to investigate the comorbid antidepressant-like and anxiolytic-like effects of ethanol extract from T.chebula fruit using experimental behavioral tests in mice. In addition, the study explored the effects of extract on monoamine oxidase -A (MAO-A) levels in mouse brain. Two doses of the T.chebula extract (100 or 200 mg/kg, p.o.) were treated continuously for fifteen days to mice. Regarding antidepressant-like effects, the treatment of T.chebula extract at both dose (100 or 200 mg/kg, p.o.) levels resulted with significant (p < 0.001) reduction in duration of immobility time and increase in swimming time as compared to control group in forced swimming test. Moreover, both doses declined the duration of immobility time in the tail suspension test and increased the number of crossing in the center area using open-field test. Additionally, the dose 200 mg/kg treatment showed a significant reduction (p < 0.05) in MAO-A activity in mouse brain. For anxiolytic activity, both doses significantly (p < 0.001) improved the time spent in open arm and the number of head dips in elevated plus maze test. The higher duration of time spent in light chamber and higher number of crossing between the light and dark chambers by extract treatment in light-dark box test also supported the anxiolytic behavior. The obtained results supported the antidepressant-like and anxiolytic-like effects of ethanol extract of T.chebula in mice.

Menhaden fish oil attenuates postpartum depression in rat model via inhibition of NLRP3-inflammasome driven inflammatory pathway.

BACKGROUND AND AIM: Postpartum depression (PPD) is a familiar problem which is associated with about 10-20% of women after child delivery. Fish oil (FO) has a therapeutic potentials to many diseases including mood disorders. However, there is paucity of data on the effects of FO supplementation on PPD rat model. Hence, this study aimed at investigating the potentials of FO in ameliorating depressive-like behaviors in PPD rat by evaluating the involvement of NLRP3-inflammasome. EXPERIMENTAL PROCEDURE: Thirty six virgin adult female rats (n = 6) were randomly divided into six groups; Group 1-3 were normal control (NC), Sham (SHAM) and ovariectomized group (OVX) respectively whereas group 4-6 were PPD rats forced-fed once daily with distilled water (PPD), fish oil (PPD + FO; 9 g/kg) and Fluoxetine (PPD + FLX; 15 mg/kg) respectively from postpartum day 1 and continued for 10 consecutive days. Rats behaviors were evaluated on postpartum day 10 through open field test (OFT) and forced swimming test (FST), followed by biochemical analysis of NLRP3 inflammasome proteins pathway in their brain and determination of neutrophil to lymphocyte ratio (NLR). RESULTS: PPD-induced rats exhibited high immobility and low swimming time in FST with increased inflammatory status; NLR, IL-1ß and NFкB/NLRP3/caspase-1 activity in their hippocampus. However, administration of FO or fluoxetine reversed the aforementioned abnormalities. CONCLUSION: In conclusion, 10 days supplementation with FO ameliorated the depressive-like behaviors in PPD rats by targeting the NFкB/NLRP3/caspase-1/IL-1ß activity. This has shed light on the potential of NLRP3 as a therapeutic target in treatment of PPD in rats.

Assessment of Antidepressant-like, Anxiolytic Effects and Impact on Memory of Pimpinella anisum L. Total Extract on Swiss Albino Mice.

Mental disorders are psychological symptoms that impact multiple areas of an individual's life. Depression and anxiety are chronic illnesses described as the most prevalent stress-related mood disorders that cause injury and early death. In Morocco, Anise "Pimpinella anisum L." is one of the most traditionally used condiment plants, which has long been used to cure various illnesses and in phytotherapy. The present study was designed to investigate the antidepressant, anxiolytic, and memory impact of the total extract of Pimpinella anisum (PATE) at the doses of 100 and 200 mg/kg, using the Forced Swimming Test (FST), Tail Suspension Test (TST), Open Field Test (OFT), and Light-Dark Box Test (LDBT) as an experimental paradigm of anxiety and depression, and Novel Object Recognition Test (NORT) and the Morris Water Maze Test (MWMT) as memory tests on Swiss albino mice. The tests were carried out on the 1st, 7th, 14th, and the 21st days of the study, and the extract groups were compared with normal controls and positive controls (receiving bromazepam and paroxetine at the doses of 1 mg/kg and 11.5 mg/kg for anxiety and depression, respectively). The daily oral gavage of the mice by the PATE induced a significant anxiolytic and antidepressant-like effect by shortening immobility time and decreasing downtime in the different tests. PATE at both doses was shown to have no impact on memory following the NORT and MWM tests. Different compounds, such as gallic acid, catechin, chlorogenic acid, caffeic acid, oleuropein, p-coumaric acid, trans-4-hydroxy-3-methoxycinnamic acid, myricetin, and quercetin, were identified during the phytochemical analysis carried out using HPLC analysis. This research supports and promotes the extract's traditional use, suggesting its use as a phytomedicine against depression and anxiety, and calls for further research to clarify its mode of action.

Salvia officinalis and Lippia triphylla: Chemical characterization and evaluation of antidepressant-like activity.

Salvia officinalis (Lamiaceae) and Lippia triphylla (Verbenaceae) are two plants known for their therapeutic effects in conventional medicine for the treatment of a wide extent of diseases, including the ones on the central nervous system. In the present study, the impact of aqueous extract from the leaves of these two herbs for the treatment of depression was examined. The phytochemical profile highlighted the presence of eighteen and ten polyphenolic compounds in Salvia officinalis and Lippia triphylla, respectively. The antidepressant effects of such extracts were assessed using two tests: the forced swimming test (FST) and tail suspension test (TST) in swiss albino mice. Five mice were partitioned into each group: control (distilled water), standard (Imipramine hydrochloride, 25 mg/kg) and three test ones treated with increased doses of aqueous extracts (250-500-1000 mg/kg), orally administered for two weeks. The acute treatment of the mice with aqueous extracts of Salvia officinalis and Lippia triphylla reduced significantly the time of immobility in the forced swimming test (p < 0.001) as compared to control group, and also decreased significantly the time of immobility of mice in the tail suspension test (p < 0.001). The findings attained in this work show how both plants possess potential anti-depressant-like effects; however, the translation from the results presented in this work to a potential use as therapeutic agents would require the acquisition of a stronger scientific evidence.

Antioxidant and antifatigue effect of a standardized fraction (HemoHIM) from Angelica gigas, Cnidium officinale, and Paeonia lactiflora.

CONTEXT: HemoHIM is an herbal preparation containing Angelica gigas Nakai (Apiaceae), Cnidium officinale Makino (Umbelliferae), and Paeonia lactiflora Pallas (Paeoniaceae) developed for immune regulation. To date, studies on the antifatigue effects of HemoHIM have not been conducted. OBJECTIVE: The antifatigue effects of HemoHIM using models of citrinin and exercise-induced chronic fatigue syndrome were investigated. MATERIALS AND METHODS: Citrinin-induced L6 skeletal muscle cells were treated with HemoHIM (125, 250, and 500 µg/mL). The antioxidant factors were analysed. ICR mice were divided into four groups (n = 10): control, HemoHIM 250, 500 mg/kg, and creatine 300 mg/kg, respectively. Mice were orally administered HemoHIM or creatine for three weeks; during this time, both rotarod test and forced swimming test (FST) were conducted. The latency time was investigated and antioxidant, antifatigue factors were analysed. RESULTS: HemoHIM significantly restored reduced antioxidant enzymes (SOD, CAT, Txn, GPx, GSr, and GCLC in HemoHIM 500 µg/mL) compared to the citrinin group in L6 cells. In vivo, HemoHIM significantly improved the latency time (FST; 279.88 ± 50.32 sec, rotarod test; 552.35 ± 23.50 sec in HemoHIM 500 mg/kg). Moreover, the FST-induced reduction in glucose and glutathione significantly increased by 3-fold (HemoHIM 500 mg/kg) and increase in LDH and MDA were significantly inhibited by 1.6, 2.1-fold in the HemoHIM 500 mg/kg compared to the control group.

Micro-Vesicles of Moringa oleifera Seeds in Heterozygous Rats for DAT Gene: Effects of Oral Intake on Behavioral Profile and Hematological Parameters.

Previous studies have shown multiple biological properties of Moringa oleifera, a plant native to Africa and Asia. In the present study, potential physiological properties of microvesicles extracted from Moringa oleifera seeds were assessed. For this purpose, we investigated behavioral profile and hematological parameters in a recent rat model characterized by dysregulation in dopamine transporter, a key regulator of dopaminergic system. Experimental design consisted of male Wistar-DAT rats aged between two and four months: wild-type (WT) (n = 5) and heterozygous (DATHET) (n = 4) control groups, which drank tap water; WT (n = 5) and DATHET (n = 6) groups which drank a solution of Moringa microvesicles and water (2: 68 mL per day), which was orally administered for two months. Rats were monitored for spontaneous locomotor activity on a 24/7 basis. In the early lit hours, treated DATHET subjects showed higher locomotor activity, proposing a sleep-delay effect of Moringa. In forced swimming test, WT subjects who took Moringa exhibited more depressive behavior. In DATHET rats, Moringa seemed to potentiate the struggle to find a way out, counteracting an initial panic. Hemoglobin and hematocrit underwent opposite changes in either genotype, supporting the opposite effects on behavioral phenotype observed. Future work is clearly needed to further explore these preliminary profiles.

Short- and Long-Term Effects of Vitamin D Treatment on Bacillus Calmette-Guerin-Induced Depressive-Like Behavior in Mice.

PURPOSE: Depression is one of the most common psychological disorders. The nutritional etiology of the depression proposes that vitamin D may play a significant role in the pathogenesis of depression. Further, vitamin D deficiency has been found to aggravate depression in animals. Therefore, vitamin D treatment might be a potential therapeutic aid in depression management. This study aimed to explore the antidepressant effects of vitamin D in a Bacillus Calmette-Guerin (BCG)-induced depression model. METHODS: Thirty-six mice were randomly assigned to short-term and long-term experimental groups. In each group, mice were randomly subcategorized into three subgroups: 1. control (received vehicle), 2. BCG (received BCG [107 CFU/mouse]), and 3. BCG + vitamin D (received vitamin D [60.000 IU/kg] before BCG [107 CFU/mouse] inoculation). After completion of the two experimental periods (3 days for the short-term group and 2 weeks for the long-term group), the mice underwent three behavioral tests: locomotor activity, the forced swimming test (FST), and the tail suspension test (TST). RESULTS: Locomotor activity did not significantly differ among the subgroups in either the long-term or short-term groups. In the short-term group, the total immobility time on the FST was decreased in the vitamin D-treated group compared to the BCG group. However, in the TST, no significant difference was found between the vitamin D-treated group and the BCG group. In the long-term group, the immobility time on the FST was decreased in the vitamin D-treated group compared to the BCG group. Similarly, the total immobility time on the TST was also significantly lower in the vitamin D-treated mice than in the BCG-treated mice. CONCLUSION: Vitamin D is useful in the management of depressive behavior. The potential role of vitamin D in the etiology of depression should be investigated in future work.

Xanthotoxin affects depression-related behavior and neurotransmitters content in a sex-dependent manner in mice.

The present study aimed to evaluate xanthotoxin's influence on male and female Swiss mice's depression-like behaviors and investigate the potential mechanism of this effect. Naturally derived furanocoumarin (the Apiaceae family), xanthotoxin, administered acutely (12.5 mg/kg), diminished the immobility level in the forced swim test only in males. The immobility level was lower in females than males, which may be associated with a higher serotonin level in the female prefrontal cortex. A dose-dependent increase of serotonin and noradrenaline was reported in the reverse-phase ion-pair liquid chromatography in the female prefrontal cortex but not in the hippocampus. We suggest that xanthotoxin may exert antidepressant properties and affect males and females differently. The increasing level of serotonin in the male and female prefrontal cortex may underlie this effect.

Possible Involvement of the IL-6/JAK2/STAT3 Pathway in the Hypothalamus in Depressive-Like Behavior of Rats Exposed to Chronic Mild Stress.

INTRODUCTION: The interleukin-6/janus kinase 2/signal transducer and activator of transcription 3 (IL-6/JAK2/STAT3) pathway plays an important role in immune function, but little research has focused on this pathway in depression. We sought to examine the relationship between the IL-6/JAK2/STAT3 pathway and depressive-like behavior. METHODS: Using a chronic mild stress (CMS) paradigm, a total of 36 adult male Sprague-Dawley rats were divided into four matched groups: (1) control + vehicle, (2) CMS + vehicle, (3) control + paroxetine, and (4) CMS + paroxetine. We investigated the effects of CMS on depressive-like behavior by using the forced swimming test (FST). Subsequently, the mRNA levels of members of the IL-6/JAK2/STAT3 pathway were assessed by qRT-PCR. RESULTS: We found that rats exposed to CMS displayed a significant increase in immobility time and a decrease in climbing time in the FST. Moreover, mRNA levels of IL-6, JAK2, and STAT3 in the hypothalamus were increased following CMS. We also found that mRNA levels of IL-6, JAK2, and STAT3 were normalized by paroxetine administration, which coincided with normalization of the depressive-like behavior. CONCLUSIONS: The IL-6/JAK2/STAT3 pathway may be activated in depression, and targeting this pathway may provide a novel effective therapeutic approach for the treatment of depression.

Subacute Assessment of the Toxicity and Antidepressant-Like Effects of Origanum Majorana L. Polyphenols in Swiss Albino Mice.

Origanum majorana L. is a plant commonly used in folk medicine to treat depression and several neurological disorders. This study aims to evaluate the antidepressant-like effect of the Origanum majorana L. polyphenols (OMP) obtained from the aerial parts using two different depression model tests: The forced swimming test (FST) and the tail suspension test (TST) in Swiss albino mice. The experiments were performed on days 1, 7, 14, and 21 with daily administration of different treatments. Two different doses were chosen for this study (50 and 100 mg/kg), and paroxetine was used as a positive control. Immobility as a consequence of the depression state was significantly reduced following the treatment with OMP, indicating an antidepressant effect. A subacute toxicity study was also performed following the Organization for Economic Co-operation and Development (OECD) Guidelines (407), showing no sign of toxicity for the studied doses. The phytochemical screening revealed the presence of 12 components, all belonging to polyphenols: Arbutin, rosmarinic acid, ursolic acid, quercetin-3-O-glucoside, quercetin-7-O-glucuronic acid, luteolin-7-O-glucoside, kaempferol-3-0-glucuronic acid, Kaempferol-3-0-pentose, caffeic acid, catechin, quercetin, and rutin. These findings suggest that O. majorana has interesting antidepressant-like properties, which deserve further investigation.

Anti-stress effects of rosemary (Rosmarinus officinalis L.) leaf extract on intestinal goblet cells and immobility of forced-swimming test in BALB/c mice.

We investigated the anti-stress effect of rosemary (Rosmarinus officinalis L.) leaf extract (RLE) on restraint-stressed mice and found that RLE alleviated decreases in the number of intestinal goblet cells and amount of hepatic triglycerides. It also decreased the immobility time in the forced-swimming test and activation of microglia in the brain, suggesting that RLE has beneficial effects on stress-induced dysfunctions.

A Synbiotic Mixture Augmented the Efficacy of Doxepin, Venlafaxine, and Fluvoxamine in a Mouse Model of Depression.

OBJECTIVES: Currently available antidepressant drugs have notable downsides; in addition to their side effects and slow onset of action their moderate efficacy in some individuals may influence compliance. Previous literature has shown that probiotics may have antidepressant effects. Introducing complementary medicine in order to augment the efficacy of therapeutic doses of antidepressant drugs appears to be very important. Therefore, the effect of adding a synbiotic mixture to drinking water was assessed in a mouse model of depression following the administration of three antidepressant drugs belonging to different classes. MATERIALS AND METHODS: The marble burying test (MBT) and forced swimming test (FST) were used as animal models of obsessive behavior and despair. The synbiotic mixture was administered to the mice's drinking water (6.25x106 CFU) for 14 days and the tests were performed 30 min after the injection of the lowest dose of doxepin (1 mg/kg), venlafaxine (15 mg/kg), and fluvoxamine (15 mg/kg) on days 7 and 14. RESULTS: After 7 days of ingestion of the synbiotic mixture, immobility time decreased in the FST for doxepin (92±5.5 s) and venlafaxine (17.3±2.5 s) compared to the control group (drinking water), but fluvoxamine decreased immobility time after 14 days of ingestion of the synbiotic mixture (70±7.5 s). Preadministration of the synbiotic mixture improved the MBT test response for venlafaxine, while it did not change the results for the other two drugs. CONCLUSION: Adding the synbiotic mixture to drinking water improved the efficacy of discrete antidepressant drugs particularly during the FST. Probiotics could be a useful complementary medicine for drug-resistant depressed individuals.

The antidepressant-like effects of Origanum majorana essential oil on mice through monoaminergic modulation using the forced swimming test.

Origanum majorana (L.) is an herb used in the treatment of diseases related to the nervous system in traditional medicine (e.g. as an anticonvulsant and sedative). The present study was conducted to investigate the antidepressant-like effects of Origanum majorana essential oil (OMEO) on mice in the forced swimming test (FST). The animals were intraperitoneally (i.p.) injected with OMEO (10-80 mg/kg) 1 h before the FST. To assess the involvement of the monoaminergic system in the antidepressant activity of OMEO, different pharmacological antagonists were administered 15 min before OMEO administration (80 mg/kg). The administration of OMEO (40 and 80 mg/kg, i.p.) decreased immobility time and increased swimming and climbing times significantly. OMEO did not cause any changes in spontaneous locomotor function in the open-field test (OFT). The pre-treatment of the animals with SCH23390, sulpiride, haloperidol, WAY100135, p-chlorophenylalanine (pCPA), ketanserin, prazosin, yohimbine, reserpine, but not propranolol, inhibited the anti-immobility effect of OMEO in the FST. A combination of sub-effective doses of fluoxetine (5 mg/kg, i.p.) or imipramine (5 mg/kg, i.p.) with OMEO (10 mg/kg, i.p.) increased the antidepressant-like effects. OMEO showed antidepressant-like effects through involvement with the dopaminergic (D1 and D2), serotonergic (5HT1A, 5-HT2A receptors) and noradrenergic (α1 and α2 adrenoceptors) systems.