Decreased Immobility Time Research Articles

Norharmane potentiated anxiolytic- and antidepressant-like responses induced by imipramine and citalopram: an isobologram analysis.

β-carboline compounds display a therapeutic property for treating depression and anxiety behaviors. Imipramine and citalopram play an important role in the modulation of anxiety and depression behaviors. We investigated the effects of norharmane, imipramine, and citalopram on anxiety- and depression-like effects and their interactions. Elevated plus maze and forced swimming test were used for the assessment of anxiety- and depression-like behaviors in male mice. The results revealed that intraperitoneal (i.p.) administration of norharmane (10 mg/kg) increased percentage of open arm time (%OAT) in the elevated plus maze test and decreased immobility time in the forced swimming test, proposing anxiolytic- and antidepressant-like effects. Injection of imipramine (5 mg/kg; i.p.) enhanced %OAT and decreased immobility time, suggesting anxiolytic- and antidepressant-like effects. Moreover, norharmane potentiated the anxiolytic- and antidepressant-like responses induced by imipramine by increasing %OAT and decreasing immobility time. The results revealed additive anxiolytic- and antidepressant-like effects between norharmane and imipramine in mice. Alone, the administration of citalopram (5 mg/kg; i.p.) enhanced %OAT and reduced immobility time, causing anxiolytic- and antidepressant-like effects. When citalopram and norharmane were coinjected, norharmane augmented the anxiolytic- and antidepressant-like effects induced by citalopram by increasing %OAT and reducing immobility time. These results indicated additive anxiolytic- and antidepressant-like effects between norharmane and antidepressant drugs such as imipramine and citalopram on the modulation of anxiety and depression processes in mice.

A Selective Nuclear Factor-κB Inhibitor, JSH-23, Exhibits Antidepressant-like Effects and Reduces Brain Inflammation in Rats.

Accumulating evidence suggests that nuclear factor (NF)-κB is involved in the pathophysiology of mood disorders. We conducted two experimental protocols in rats to investigate the effects of a selective NF-κB inhibitor (JSH-23) on (i) lipopolysaccharide (LPS)-induced inflammation and (ii) on behavioral phenotypes in rat models of depression (sucrose consumption test and forced swim test) and mania (amphetamine-induced hyperactivity test). Additionally, we tested the effects of JSH-23 on levels of inflammatory components (interleukin-6, prostaglandin E2, nuclear phospho-p65, and tumor necrosis factor-α) in the brain. Acute treatment with JSH-23 (10 mg/kg, intraperitoneally [ip]) led to potent anti-inflammatory effects in LPS-treated rats, including a diminished hypothermic response to LPS and a reduction in pro-inflammatory mediators' levels in the brain. Chronic treatment with JSH-23 (3 mg/kg, ip, once daily, for 14 days) resulted in robust antidepressant-like effects (increased sucrose consumption and decreased immobility time). The antidepressant-like effects of JSH-23 were mostly accompanied by a reduction in levels of pro-inflammatory mediators in the brain. On the other hand, JSH-23 did not reduce amphetamine-induced hyperactivity. Altogether, these data suggest that NF-κB may be a potential therapeutic target for pharmacological interventions for depression.

Ameliorating Effect of Standardized Rice Bran Supplement on Depressive-Like Behaviors in Ovariectomized Mice.

Menopausal depression, often associated with hormonal fluctuations such as decreased estrogen levels, imposes significant mental health burdens. Despite the antidepressant biological properties of standardized rice bran supplement (RBS), its impact on menopausal depression and underlying mechanisms remains largely unexplored. In this study, we investigated the antidepressant effects of RBS in a mouse model of estrogen deficiency-induced depression. Ovariectomized (OVX) mice received oral doses of RBS (250 and 1000 mg/kg) and 17β estradiol over a 20-week period. RBS administration resulted in decreased immobility time in the tail suspension and forced swim tests, along with increased locomotor activity in the open field test. Furthermore, RBS enhanced nitric oxide production and neuronal nitric oxide synthase (nNOS) expression in the hippocampi of OVX mice. Additionally, RBS administration phosphorylated extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), and tropomyosin receptor kinase B and increased the protein expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. These findings suggest that RBS alleviated depressive behaviors in OVX mice by augmenting hippocampal nNOS expression and activating the ERK-CREB-BDNF signaling pathway. Therefore, based on these results, we propose that RBS is a promising agent to treat menopausal depression, a challenging condition.

Antidepressant potential of β-caryophyllene in maternal separation-induced depression-like in mice: A focus on oxidative stress and nitrite levels

BackgroundMajor depressive disorder is prevalent across different societies, affecting individuals from various cultural and socioeconomic backgrounds. Dysregulation of the nitric oxide (NO) pathway and increased oxidative stress have been implicated as contributing factors. PurposeThis study aimed to explore the antidepressant potential of β-caryophyllene in a mouse model subjected to maternal separation stress, with a focus on its effects on oxidative stress and nitrite levels. Study DesignThe research involved 40 male mice, which were divided into five groups. MethodsThe control group received 1 ml/kg of normal saline, while the maternal separation (MS) groups were administered normal saline in conjunction with β-caryophyllene at doses of 10, 20, and 50 mg/kg. Various behavioral tests, including the open field test (OFT), forced swimming test (FST), and splash test, were employed to assess the impact of β-caryophyllene. Additionally, measurements of total antioxidant capacity (TAC), malondialdehyde (MDA), and nitrite levels in the hippocampus were conducted. ResultsThe findings demonstrated that maternal separation stress induced depressive-like behaviors in mice, as evidenced by increased immobility time in the FST and decreased grooming behavior in the splash test. Furthermore, MS was associated with elevated MDA and nitrite levels and reduced TAC in the hippocampus. However, administration of β-caryophyllene increased grooming activity in the splash test and decreased immobility time in the FST. Additionally, β-caryophyllene exhibited antioxidant properties, lowering MDA and nitrite levels while enhancing TAC in the hippocampus. ConclusionThese results suggest that β-caryophyllene may possess antidepressant-like effects in mice subjected to maternal separation, likely due to its antioxidant actions in the hippocampus.

A novel probiotic formula, BLLL, ameliorates chronic stress-induced depression-like behaviors in mice by reducing neuroinflammation and increasing neurotrophic factors.

Introduction: Probiotics have been recognized for their various biological activities, including antioxidant and anti-inflammatory properties. This study investigates the therapeutic effect of a novel probiotic formula, BLLL, consisting of Bifidobacterium breve, Lactobacillus plantarum, Lactobacillus paracasei, and Lactobacillus helveticus, on chronic stress-induced depression-like behaviors in mice. Methods: The BLLL formula or phosphate-buffered saline (PBS) was given orally at a dose of 2, 4, or 8 × 1010 CFU/kg once daily for 10days in mice treated with chronic unpredictable stress (CUS) treated or vehicle. Depression-like behaviors were assessed using the sucrose preference test (SPT), the forced swimming test (FST), and the tail suspension test (TST). The mRNA and/or protein expression of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), IL-4, IL-10, and chitinase-3-like protein 3 (CHI3L1, also known as Ym-1), as well as the concentration of nitrite, malondialdehyde (MDA), glutathione (GSH), and brain-derived neurotrophic factor (BDNF) in the hippocampus and medial prefrontal cortex were examined. Results: The BLLL formula treatment at a dose of 8 × 1010 CFU/kg, but not at a dose of 2 or 4 × 1010 CFU/kg, improved CUS-induced depression-like behaviors in mice, as shown by the decrease in immobility time in the TST and FST and the increase in sucrose intake in the SPT. Further analysis revealed that BLLL treatment suppressed the CUS-induced increase in IL-1β, IL-6, and TNF-α mRNA and protein levels, as well as the CUS-induced decrease in IL-4, IL-10, and Ym-1 mRNA and/or protein levels in the hippocampus and medial prefrontal cortex. In addition, treatment with the BLLL formula countered the CUS-induced increase in nitrite and MDA levels and the CUS-induced decrease in GSH content and BDNF concentration in the hippocampus and medial prefrontal cortex. Conclusion: These results demonstrate that the novel probiotic formula BLLL ameliorates chronic stress-induced depression-like behavior in mice by suppressing neuroinflammation and oxido-nitrosative stress in the brain.

Examination of the Effect of Dimethyl Trisulfide in Acute Stress Mouse Model with the Potential Involvement of the TRPA1 Ion Channel.

Polysulfides are endogenously produced in mammals and generally associated with protective functions. Our aim was to investigate the effect of dimethyl trisulfide (DMTS) in a mouse model of acute stress. DMTS activates transient receptor potential ankyrin 1 (TRPA1) channels and leads to neuropeptide release, potentially that of substance P (SP). We hypothesize that DMTS might inhibit the degrading enzymes of endocannabinoids, so this system was also investigated as another possible pathway for mediating the effects of DMTS. Trpa1 gene wild-type (WT) and knockout (KO) mice were used to confirm the role of the TRPA1 ion channel in mediating the effects of DMTS. C57BL/6J, NK1 gene KO, and Tac1 gene KO mice were used to evaluate the effect of DMTS on the release and expression of SP. Some C57BL/6J animals were treated with AM251, an inhibitor of the cannabinoid CB1 receptor, to elucidate the role of the endocannabinoid system in these processes. Open field test (OFT) and forced swim test (FST) were performed in each mouse strain. A tail suspension test (TST) was performed in Trpa1 WT and KO animals. C-FOS immunohistochemistry was carried out on Trpa1 WT and KO animals. The DMTS treatment increased the number of highly active periods and decreased immobility time in the FST in WT animals, but had no effect on the Trpa1 KO mice. The DMTS administration induced neuronal activation in the Trpa1 WT mice in the stress-related brain areas, such as the locus coeruleus, dorsal raphe nucleus, lateral septum, paraventricular nucleus of the thalamus, and paraventricular nucleus of the hypothalamus. DMTS may have a potential role in the regulation of stress-related processes, and the TRPA1 ion channel may also be involved in mediating the effects of DMTS. DMTS can be an ideal candidate for further study as a potential remedy for stress-related disorders.

Shikonin ameliorates depressive- and anxiogenic-like behaviors in rats via the suppression of inflammation in the hippocampus

Shikonin is an active naphthoquinone with antioxidative, anti-inflammatory, and anticancer properties. In this study, we investigated the effects of shikonin on depressive- and anxiety-like behaviors in lipopolysaccharide- (LPS-) induced depression and chronic unpredictable mild stress (CUMS) rat models and explored the potential mechanism. First, a 14-day intraperitoneal administration of shikonin (10 mg/kg) significantly decreased immobility time in forced swimming test (FST) and increased open arm entries in elevated plus maze (EPM) test, without affecting line crossings in open field test (OFT), indicating that shikonin has anti-depressant- and anxiolytic-like effects. Second, chronic shikonin administration (10 mg/kg) reversed depressive- and anxiety-like behaviors in LPS-induced and CUMS depression models, as shown in the sucrose preference test (SPT), FST, EPM, and novel object recognition test (NORT). Finally, shikonin significantly reduced the levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) in hippocampus, indicating that the anti-depressant- and anxiolytic-like effects of shikonin are related to the reduction of neuroinflammation in hippocampus. These findings suggest that shikonin exerts anti-depressant- and anxiolytic-like effects via an anti-inflammatory mechanism of shikonin in the hippocampus.

L-type calcium channel regulation of depression, anxiety and anhedonia-related behavioral phenotypes following chronic stress exposure

Exposure to chronic and unpredictable stressors can precipitate mood-related disorders in humans, particularly in individuals with pre-existing mental health challenges. L-type calcium channels (LTCCs) have been implicated in numerous neuropsychiatric disorders, as LTCC encoding genes have been identified as candidate risk factors for neuropsychiatric illnesses. In these sets of experiments, we sought to examine the ability of LTCC blockade to alter depression, anxiety, and anhedonic-related behavioral responses to chronic unpredictable stress (CUS) exposure in female and male rats. Rats first underwent either 21 days of CUS or no exposure to chronic stressors, serving as home cage controls (HCC). Then rats were examined for anhedonia-related behavior, anxiety and depression-like behavioral responses as measured by the sucrose preference test (SPT), elevated plus maze (EPM), and forced swim test (FST). CUS exposed females and males showed anhedonic and anxiogenic-like behavioral responses on the SPT and EPM, respectively, when compared to HCCs. In female and male rats, systemic administration of the LTCC blocker isradipine (0.4 mg/kg and 1.2 mg/kg, I.P.) attenuated the CUS-induced decrease in sucrose preference and reversed the CUS-induced decrease in open arm time. In the FST, systemic isradipine decreased immobility time across all groups, consistent with an antidepressant-like response. However, there were no significant differences in forced swim test immobility time between HCC and CUS exposed animals. Taken together, these data point to a role of LTCCs in the regulation of mood disorder-related behavioral phenotype responses to chronic stress exposure.

Protective effect of melatonin against metabolic disorders and neuropsychiatric injuries in type 2 diabetes mellitus mice

BackgroundType 2 diabetes mellitus (T2DM) is a metabolic disease characterized by hyperglycemia and progressive cognitive dysfunction, and our clinical investigation revealed that the plasma concentration of melatonin (Mlt) decreased and was closely related to cognition in T2DM patients. However, although many studies have suggested that Mlt has a certain protective effect on glucose and lipid metabolism disorders and neuropsychiatric injury, the underlying mechanism of Mlt against T2DM-related metabolic and cognitive impairments remains unclear. PurposeThe aim of the present study was to investigate the therapeutic effect of Mlt on metabolic disorders and Alzheimer's disease (AD)-like neuropsychiatric injuries in T2DM mice and to explore the possible underlying molecular mechanism involved. MethodsA T2DM mouse model was established by a combination of a high-fat diet (HFD) and streptozotocin (STZ, 100 mg/kg, i.p.), and Mlt (5, 10 or 20 mg/kg) was intragastrically administered for six consecutive weeks. The serum levels of glycolipid metabolism indicators were measured, behavioral performance was tested, and the protein expression of key molecules involved in the regulation of synaptic plasticity, circadian rhythms, and neuroinflammation in the hippocampus was detected. Moreover, the fluorescence intensities of glial fibrillary acidic protein (GFAP), ionized calcium binding adapter molecule 1 (IBA-1), amyloid β-protein (Aβ) and phosphorylated Tau (p-Tau) in the hippocampus were also observed. ResultsTreatment with Mlt not only improved T2DM-related metabolic disorders, as indicated by increased serum concentrations of fasting blood glucose (FBG), glycosylated hemoglobin (HbAlc), insulin (INS), total cholesterol (TC) and triglyceride (TG), improved glucose tolerance and liver and pancreas function but also alleviated AD-like neuropsychiatric injuries in a HFD/STZ-induced mouse model, as indicated by decreased immobility time in the tail suspension test (TST) and forced swimming test (FST), increased preference indices of novel objects or novel arms in the novel object recognition test (NOR) and Y-maze test (Y-maze), and improved platform positioning capability in the Morris water maze (MWM) test. Moreover, treatment with Mlt also improved the hyperactivation of astrocytes and microglia in the hippocampus of mice, accompanied by reduced expression of interleukin 1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor (TNF-α), Aβ, and p-Tau and increased expression of brain-derived neurotrophic factor (BDNF), Synapsin I, Synaptotagmin I, melatonin receptor 1B (MT1B), brain muscle arnt-like protein 1 (Bmal1), circadian locomotor output cycles kaput (Clock), period 2 (Per2), and cryptochrome 2 (Cry2). ConclusionMlt alleviated T2DM-related metabolic disorders and AD-like neuropsychiatric injuries in a HFD/STZ-induced mouse model, possibly through a mechanism involving the regulation of glial activation and associated neuroinflammation and the balancing of synaptic plasticity and circadian rhythms in the hippocampus.

Integrated network pharmacology analysis and experimental validation to investigate the mechanism of Flavan-3-ols and aromatic resins in depression.

The present investigation delved into the pharmacological mechanisms underlying the management of depression through Flavan-3-ols and Aromatic Resins, employing in silico and in vivo methodologies. Network pharmacology was utilized to identify targets associated with the antidepressant activity of Flavan-3-ols and Aromatic Resins. Protein-protein interaction and KEGG analyses were conducted to enrich and explore key pathways. Molecular docking and simulation studies were executed to assess the targets. The antidepressant effects were studied using the Forced Swim Test and Tail Suspension Test on both unstressed mice and those subjected to the chronic unpredictable mild stress (CUMS) paradigm. The Compound-Target network analysis revealed a substantial impact of the components on numerous targets, with 332 nodes and 491 edges. Protein-protein interaction analysis indicated significant interactions with targets implicated in depression. KEGG analysis highlighted major pathways, including neuroactive ligand-receptor interaction, dopaminergic synapse, and long-term depression. Docking studies on EGCG demonstrated binding energies of -7.2kcal/mol for serotonin 1A (5-HT1A), -7.9kcal/mol for D2, and - 9.6kcal/mol for MOA-A. Molecular dynamics simulation indicated minute fluctuation, hence suggesting stable complexes formed between small molecules and proteins. The combination of Flavan-3-ols and Aromatic Resins significantly increased mobility time (p < 0.05) in the Forced Swim Test and Tail Suspension Test, while significantly decreasing immobility time and time freezing (p < 0.05) in both unstressed and CUMS mice. This study demonstrated the antidepressant characteristics of Flavan-3-ols and Aromatic Resins, underscoring the need for further research to develop a novel antidepressant medication.

Bacillus coagulans and Clostridium butyricum synergistically alleviate depression in a chronic unpredictable mild stress mouse model through altering gut microbiota and prefrontal cortex gene expression

Introduction: The prevalence of major depressive disorder (MDD) has gradually increased and has attracted widespread attention. The aim of this study was to investigate the effect of a probiotic compound consisting of Bacillus coagulans and Clostridium butyricum, on a mouse depression model.Methods: Mice were subjected to chronic unpredictable mild stress (CUMS) and then treated with the probiotics at different concentrations. And mice received behavior test such as forced swimming test and tail suspension test. After that, all mice were sacrificed and the samples were collected for analysis. Moreover, prefrontal cortex (PFC) gene expression and the gut microbiota among different groups were also analyzed.Results: Probiotics improved depressive-like behavior in CUMS mice, as indicated by decreased immobility time (p &amp;lt; 0.05) in the forced swimming test and tail suspension test. probiotics intervention also increased the level of 5-hydroxytryptamine (5-HT) in the prefrontal cortex and decreased the adrenocorticotropic hormone (ACTH) level in serum. In addition, by comparing the PFC gene expression among different groups, we found that the genes upregulated by probiotics were enriched in the PI3K-Akt signaling pathway in the prefrontal cortex. Moreover, we found that downregulated genes in prefrontal cortex of CUMS group such as Sfrp5 and Angpt2, which were correlated with depression, were reversed by the probiotics. Furthermore, the probiotics altered the structure of the gut microbiota, and reversed the reduction of cob(II)yrinate a,c-diamide biosynthesis I pathway in CUMS group. Several species like Bacteroides caecimuris and Parabacteroides distasoni, whose abundance was significantly decreased in the CUMS group but reversed after the probiotics intervention, showed significantly positive correlation with depression associated genes such as Tbxas1 and Cldn2.Discussion: These findings suggested that CUMS-induced depression-like behavior can be alleviated by the probiotics, possibly through alterations in the PFC gene expression and gut microbiota.

The antidepressant efficacy of flurbiprofen in mice: Behavioural assessment

Flurbiprofen is a nonsteroidal anti-inflammatory medication (NSAID). The psychological effect of nonsteroidal anti-inflammatory drugs (NSAIDs) is a source of contention based on clinical and experimental evidence. As a result, the goal of our study was to assess the antidepressant effects of various flurbiprofen doses in mice. We evaluated the effect of oral administration of flurbiprofen at 10, 20, and 40 mg/kg in the tail suspension and forced swimming tests after 1 h of treatment. Fluoxetine (10 mg/kg, i.p.) was used as a positive control. Flurbiprofen at 40 mg/kg showed a significant antidepressant effect, which was revealed by a significant decrease in immobility time compared with the control group, with the group administered flurbiprofen at 10 mg/kg, and with the group given flurbiprofen at 20 mg/kg in the tail suspension test. Flurbiprofen at 40 mg/kg showed an antidepressant effect, which was revealed by a significant decrease in immobility time compared with the control group and with the group given flurbiprofen at 10 mg/kg. Flurbiprofen at 20 mg/kg had a minimal antidepressant effect in the swimming forced test, which was reflected by a non-significant decrease in immobility time compared with the control group. In conclusion, our results showed that relatively high therapeutic doses of flurbiprofen might have an antidepressant effect in a mouse model, and we recommended conducting other in vivo studies to clarify the variation in dose response.

Serotonin transporter knockdown relieves depression-like behavior and ethanol-induced CPP in mice after chronic social defeat stress

Patients with stress-triggered major depression disorders (MDD) can often seek comfort or temporary relief through alcohol consumption, as they may turn to it as a means of self-medication or coping with overwhelming emotions. The use of alcohol as a coping mechanism for stressful events can escalate, fostering a cycle where the temporary relief it provides from depression can deepen into alcohol dependence, exacerbating both conditions. Although, the specific mechanisms involved in stress-triggered alcohol dependence and MDD comorbidities are not well understood, a large body of literature suggests that the serotonin transporter (SERT) plays a critical role in these abnormalities. To further investigate this hypothesis, we used a lentiviral-mediated knockdown approach to examine the role of hippocampal SERT knockdown in social defeat stress-elicited depression like behavior and ethanol-induced place preference (CPP). The results showed that social defeat stress-pro depressant effects were reversed following SERT knockdown demonstrated by increased sucrose preference, shorter latency to feed in the novelty suppressed feeding test, and decreased immobility time in the tail suspension and forced swim tests. Moreover, and most importantly, social stress-induced ethanol-CPP acquisition and reinstatement were significantly reduced following hippocampal SERT knockdown using short hairpin RNA shRNA-expressing lentiviral vectors. Finally, we confirmed that SERT hippocampal mRNA expression correlated with measures of depression- and ethanol-related behaviors by Pearson’s correlation analysis. Taken together, our data suggest that hippocampal serotoninergic system is involved in social stress-triggered mood disorders as well as in the acquisition and retrieval of ethanol contextual memory and that blockade of this transporter can decrease ethanol rewarding properties.

Investigating the Protective Effects of a Tryptophan-Based Diet in Alcoholics: An Experimental Study on Depression and Anxiety

Depression and anxiety are prevalent co-morbidities among individuals with chronic alcohol consumption, posing significant health challenges worldwide. This study aimed to explore the potential protective effects of a tryptophan-based diet against depressive tendencies and anxiety associated with chronic alcohol consumption. Using an experimental design, Wistar rats were subjected to chronic alcohol administration along with varying doses of a tryptophan-based diet over 28 days. Behavioral tests including the Elevated Plus Maze (EPM) and Forced Swim Test (FST) were conducted to evaluate anxiety-like behavior and depressive tendencies, respectively. Results indicated a significant decrease in immobility time in the FST with increasing doses of the tryptophan-based diet, suggesting antidepressant effects. Moreover, the anxiety index decreased while the time spent on open arms increased with higher doses of the diet in the EPM, indicating anxiolytic effects. These findings suggest that a high tryptophan-based diet could serve as a potential intervention for individuals with alcohol-related depression and anxiety. Keywords: Depression, anxiety, alcohol, tryptophan, diet, alcoholics

Anethole as a promising antidepressant for maternal separation stress in mice by modulating oxidative stress and nitrite imbalance

The occurrence of major depressive disorder is widespread and can be observed in individuals belonging to all societies. It has been suggested that changes in the NO pathway and heightened oxidative stress may play a role in developing this condition. Anethole is a diterpene aromatic compound found in the Umbelliferae, Apiaceae, and Schisandraceae families. It has potential pharmacological effects like antioxidant, anxiolytic, analgesic, anti-inflammatory, antidiabetic, gastroprotective, anticancer, estrogenic, and antimicrobial activities. This study aimed to investigate the potential antidepressant properties of Anethole in a mouse model experiencing maternal separation stress while also examining its impact on oxidative stress and nitrite levels. The research involved the participation of 40 male NMRI mice, separated into five distinct groups to conduct the study. The control group was administered 1 ml/kg of normal saline, while the MS groups were given normal saline and Anethole at 10, 50, and 100 mg/kg doses. The study comprised various behavioural tests, including the open field test (OFT), forced swimming test (FST), and splash test, to assess the effects of Anethole on the mice. In addition to the behavioural tests, measurements were taken to evaluate the total antioxidant capacity (TAC), malondialdehyde (MDA), and nitrite levels in the hippocampus of the mice. According to the findings, maternal separation stress (MS) led to depressive-like conduct in mice, including a rise in immobility duration during the FST and a reduction in the duration of grooming behaviour in the splash test. Additionally, the results indicated that MS correlated with an increase in the levels of MDA and nitrite and a reduction in the TAC in the hippocampus. However, the administration of Anethole resulted in an increase in grooming activity time during the splash test and a decrease in immobility time during the FST. Anethole also exhibited antioxidant characteristics, as demonstrated by its ability to lower MDA and nitrite levels while increasing the TAC in the hippocampus. The results suggest that Anethole may have an antidepressant-like impact on mice separated from their mothers, likely partly due to its antioxidant properties in the hippocampus.

Protective role of the ginsenoside Rg1 against methimazole-induced gestational hypothyroidism on reflexive behaviors, conditioned fear and cortical antioxidant levels in mice offspring

Ginsenoside Rg1(Rg1), a monomer of a tetracyclic triterpenoid derivative, possesses diverse medicinal properties attributed to its unique chemical structure and may have beneficial effects on fetal development. This study aimed to investigate the protective effects of prenatal exposure to Rg1 against Methimazole-induced gestational hypothyroidism on reflexive behaviors, conditioned fear, and cortical antioxidant levels in mouse offspring.40 female virgin mice and 12 male NMRI mice were assigned to four groups: group 1 served as the control, group 2 received Methimazole(MMI) at a concentration of 0.02% in their drinking water, group 3 received Rg1(150 mg/kg), and group 4 received both MMI and Rg1.Groups of 2–4 were administered the substances from days 1–9 of gestation. After delivery, pups were selected, and reflexive motor behaviors and conditioned fear were assessed. Additionally, levels of brain tissue catalase(CAT), malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione peroxidase(GPx) levels were measured. Furthermore, postpartum immobility time in the forced swimming test (FST), tail suspension test (TST), and the number of squares crossed in the open field test (OFT)were determined. The results demonstrated that maternal exposure to Rg1 improved ambulation score, hind-limb suspension score, grip strength, front-limb suspension, hind-limb foot angle, negative geotaxis, surface righting, and conditioned fear in hypothyroidism-induced offspring(P<0.05). Rg1 decreased immobility time in the FST, and TST, and increased the number of squares crossed in the OFT in postpartum hypothyroidism-induced mice(P<0.05). Moreover, Rg1 reduced brain tissue MDA levels and increased brain tissue CAT, SOD, and GPx levels in mice and their offspring(P<0.05). These findings indicate that Rg1 mitigated postpartum depression in mice and improved reflexive motor behaviors in their pups.

Gynura procumbens and selected metabolites: Amelioration of depressive-like behaviors in mice and risperidone-induced hyperprolactinemia in rats

Gynura procumbens (Lour.) Merr., utilized in traditional Chinese medicine, is known for its liver-protective, liver-soothing, and depression-alleviating properties. This research examines the antidepressant and anti-hyperprolactinemia potentials of an ethanol extract from G. procumbens stems (EEGS) and specific metabolites. To model depression and hyperprolactinemia, chronic unpredictable mild stress (CUMS) was induced in mice and risperidone was administered to rats, respectively. Treatments involved administering low (5 mg/kg), medium (25 mg/kg), and high (125 mg/kg) doses of EEGS and certain metabolites to both models. Behavioral assessments were conducted in the CUMS-induced mice, while the CA3 neuronal damage in mice and histopathological alterations in rat mammary glands were evaluated using Nissl and Hematoxylin & Eosin staining techniques, respectively. EEGS decreased immobility times in the forced swimming and tail suspension tests in mice, enhancing their exploration of the central zone. It elevated the serum levels of 5-hydroxytryptamine, norepinephrine, estradiol, luteinizing hormone (LH), and testosterone in mice. Moreover, EEGS restored the neuronal cell arrangement in the CA3 area, reduced interleukin-1beta mRNA production, and increased the expression of interleukin-10 and beta-catenin mRNA. In the context of risperidone-induced hyperprolactinemia, EEGS lowered blood prolactin levels, reduced the dimensions of rat nipples, and enhanced LH, progesterone, and dopamine levels, alongside mitigating mammary hyperplasia. Among the EEGS selected metabolites, the combined effect of chlorogenic acid and trans-p-coumaric acid was found to be more effective than the action of each compound in isolation. Collectively, the findings indicate that EEGS and its selected metabolites offer promising antidepressant benefits while counteracting hyperprolactinemia.

Asperuloside Suppresses the Development of Depression through Wnt3α/GSK-3β Signal Pathway in Rats.

Depressive disorder is the most common mental disorder with significant economic burden and limited treatments. Traditional Chinese medicine monomer has emerged as a promising non-pharmacological treatment for reducing depressive symptoms. The aim of this study was to investigate the antidepressant-like effects of asperuloside (ASP) and its mechanism. The depression-like behaviors of chronic unpredictable mild stress (CUMS)-exposed rats were evaluated by behavioral tests. At the same time, the behaviors of rats treated with different concentrations of ASP (10, 20, 40 mg/kg) were also evaluated. RNA sequencing was performed to screen for dysregulated genes following ASP treatment. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was performed to state the enriched pathways. Protein expression was detected by Western blotting. With the increase of ASP concentration (over 20 mg/kg), the depression-like behaviors of the rats were alleviated, which was manifested as the increase of the number of entries in the central zone, decrease of immobility time, and the increase of swimming time, sucrose preference, and body weight. ASP activated the Wnt3α/glycogen synthase kinase 3β (GSK-3β)/β-catenin signaling pathway in vivo. Knockdown of β-catenin reversed the effects of ASP on regulating depression-like behaviors. ASP alleviates depression-like behaviors by activating the Wnt3α/GSK-3β/β-catenin signaling pathway, indicating that ASP may be a potential therapeutic drug for treatment of depression.

Antidepressant-Like Effects of Cinnamomum verum on Open-Space Forced Swim-Induced Depression in Mice.

Depression is a mental disorder characterized by depressive episodes, such as low mood, low self-esteem, feeling of guilt, and poor concentration. Depression has a high comorbidity with cognitive impairments. Studies have shown that cinnamon has anti-inflammatory antiviral, antihypertensive, antioxidant and anti-diabetic potentials. Therefore, the aim of the research was to assess the antidepressant effect of cinnamon on open-space forced swim-induced depression in mice. Twenty-five (25) Swiss albino mice were grouped into five groups (n=5). Group I: control (negative control) exposed to open-space forced swim test (OSFST) without any treatment, Groups II, III and IV received graded doses of Cinnamon 12.5, 25, and 50 mg/kg, group 5 (positive control) received fluoxetine 20 mg/kg orally. The animals were subjected to OSFST, Open Field Test (Line Crossing) and Novel Object Recognition Test (NORT). Administration of cinnamon showed decreased immobility time (behavioural despair) in OSFST compared to control and fluoxetine groups (p < 0.05). However, no statistically significant effect was observed in line crossing (locomotor activity) and the discrimination ratio of NORT (non-spatial short-term memory) between cinnamon administered groups and the control group. In conclusion, cinnamon has shown antidepressant-like effect in open-space forced swim-induced depression in mice. Keywords: Cinnamon, Depression, Cognitive impairment, Immobility time, Behavioural despair.

Fucoidan attenuates chronic colitis and behavioral deficits by reshaping gut microbiota-brain axis balance

Inflammatory bowel disease (IBD) often coexists with depression, posing considerable challenges for treatment. This study aimed to investigate the therapeutic potential of fucoidan, a compound derived from Laminaria japonica, in a dextran sulfate sodium (DSS)-induced model of IBD with comorbid depression. The administration of fucoidan demonstrated significant therapeutic efficacy, as it reduced disease activity, increased sucrose preference, and decreased immobility time, suggesting benefits for both IBD and depression. Fucoidan had a noteworthy impact on the gut microbiota, characterized by an increase in the abundance of Firmicutes and Lactobacillus. Additionally, it strengthened the integrity of the colonic barrier by upregulating tight junction proteins (ZO-1, Occludin, and Claudin-1) and reduced colonic inflammation via the TLR4/NF-κB pathway. Fucoidan also exhibited the ability to suppress peripheral inflammation and lower stress response hormone levels, particularly corticosterone. Furthermore, fucoidan reduced the number of microglia, as well as decreasing cytokines such as interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) levels, indicating a decrease in neuroinflammation in IBD-afflicted mice. In conclusion, fucoidan effectively mitigates IBD comorbid with depression by modulating the gut microbiota-brain axis. These findings offer promise for fucoidan as a natural compound to manage both IBD and associated depressive symptoms.