Anti-depressant Activity of Hydroalcoholic Extract of Asperula odorata L. in Mice

Background: The relationship between the treatment of depression and plant-derived substances (e.g., flavonoids, coumarin, and scopoletin) has been demonstrated through interference with the monoamine system. The present study was planned to evaluate the anti-depressant effects of Asperula odorata L. plant through behavioral tests in mice. Material and Methods: In this experimental study, 35 male Syrian mice weighing 30-40 g were examined in five groups (n=7) as follow: received oral distilled water gavage (control), 10 mg/kg of fluoxetine solution gavage (reference standard), 10, 5, and 2.5 mg/kg of A. odorata L. extract gavage (treatment groups). After one week, all behavioral tests, including tail suspension test (TST), forced swimming test (FST), open field test (OFT), elevated plus maze test (EPMT), and fractionation tests were performed each morning for 4-6 h within five days. Results: The hydroalcoholic extract of A. odorata contained phenolic and flavonoid substances (Shinoda test confirmed flavonoid family). Administration of extract (10 and 5 mg/kg doses) versus fluoxetine (10 mg/kg dose) reduced the immobility of animals in both FST and TST (P<0.05). At the OFT, the administered extract increased the number of central square entries of animals with higher mobility (P<0.05). At a 10 mg/kg dose, the active flavonoid ingredients increased the mice's incline to entre and spent more time within no wall parts of EPMT (P<0.05). Conclusion: Our study suggests that the hydroalcoholic extract of A. odorata L. could have significant anti-depressant activity. [GMJ.2021;10:e2206]

Evaluation of Antidepressant-like Effect of Clitoria ternatea Linn.

Depressive disorder is a prevalent psychiatric disorder, which affects 21% of the world population. The presently using drugs can impose a variety of side-effects including cardiac toxicity, hypopiesia, sexual dysfunction, body weight gain, and sleep disorder. Ayurvedic medicine may be a powerful weapon given by our nature to cure disease. Considering the importance of plants as sources of drugs even today people are adopting different herbal drugs for the treatment of assorted diseases. During the last decade, there is a growing interest in the therapeutic effects of natural products on mental disorders. This study planned to assess antidepressant like activity of methanolic extract of Clitoria ternatea Linn. (fabaceae). Soxhlet extraction method was used for methanolic extraction. Antidepressant activity was studied using forced swimming test (FST) and tail suspension test (TST). Two doses 200 and 400 mg/kg of methanolic extract of flower were selected for testing. Imipramine (10 mg/kg, i.p.) were used as the reference standard drugs. Methanolic extract of Clitoria ternatea flower significantly reduced immobility time in both TST and FST. Extract increased the climbing behavior in FST, which is similar to effect observed with imipramine. The results of this study suggest that antidepressant like effect of Clitoria ternatea seems to be mediated by an increase in norepinephrine level in synapses. However further study is needed to understand mechanism of action and to isolate the active component responsible for antidepressant like activity.

Design, Synthesis, and Antidepressant Activity Study of Novel Aryl Piperazines Targeting Both 5-HT1A and Sigma-1 Receptors

A total of 20 novel aryl piperazine derivatives were designed and synthesized, and their structures were confirmed by mass spectrometry and nuclear magnetic resonance analyses. Their 5-HT1A and sigma-1 receptor affinities were determined, and six of them showed high affinities (K i < 20 nmol/L) to both 5-HT1A and sigma-1 targets. Then, metabolic stability (T 1/2) tests of six compounds in rat and human liver microsomes were performed. Our data indicated that compound 27 has both high affinity for 5-HT1A and sigma-1 receptors (5-HT1A: K i = 0.44 nmol/L; sigma-1: K i = 0.27 nmol/L), and good metabolic stability (T 1/2 values are 21.7 and 24.6 minutes, respectively). Interestingly, results from the forced swimming test, mouse tail suspension test, and preliminary pharmacokinetic test suggested the marked antidepressant activity, good pharmacokinetic characteristics, and low toxicity of compound 27 in the two models. In conclusion, compound 27 has great value of further study as an active molecule of antidepressant drugs.

Evaluation of the Therapeutic Potential of Oral Phycocyanin-Rich Spirulina Extract in Neuropsychiatric Disorders.

Aim: Spirulina is a microalga that is widely used as a food supplement and is regarded as having performance enhancing and health promoting properties. We conducted a preliminary evaluation of the possible antidepressant, anti-anxiety, pro-socialization and cognition-enhancing effects of Spirulina in mouse models Methods: Sixty male BalbC mice aged 3 weeks were administered phycocyanin-rich Spirulina extract [PRSE, 545 mg/kg], fluoxetine [20 mg/kg] or water orally for 5 weeks. During the last 2 weeks of the experiment a series of behavioral-cognitive tests was performed to evaluate motor activity, antidepressant and anti-anxiety effects, socialization and cognitive effects. Effects of PRSE and fluoxetine were compared to those of water. Results: There was a significant effect of PRSE in the activity domain, manifesting as an increase in velocity in the open field [p=0.0007 vs. water]. Fluoxetine significantly enhanced immobility in the tail suspension test and the forced swim test reflecting the known antidepressant effect of this compound, but not PRSE. There were no significant effects of PRSE in tests of anxiety, socialization or cognition. Conclusions: The most striking observation in this study was that PRSE significantly enhanced activity in the open field test. Further studies are indicated to confirm and extend this finding and investigate possible mechanisms of action. The results of the current study do not support sporadic reports of possible antidepressant or cognition-enhancing effects of PRSE. Nevertheless, additional studies are indicated using depression models rather than naïve mice, alternative mouse strains, using additional cognitive tests, and administering higher PRSE doses.

Saccharina japonica Ethanol Extract Ameliorates Depression/Anxiety-Like Behavior by Inhibiting Inflammation, Oxidative Stress, and Apoptosis in Dextran Sodium Sulfate Induced Ulcerative Colitis Mice

Saccharina japonica is a common marine vegetable in East Asian markets and has a variety of health benefits. This study was focused on the anti-depressant/anxiety effects of Saccharina japonica ethanol extract (SJE) on dextran sodium sulfate (DSS)-induced mice and its potential mechanism in their brain. Male C57BL/6 mice were treated with mesalazine and various doses of SJE (1, 2, and 4 g/kg body weight) for 2 weeks, followed by DSS treatment at the second week. The DSS-induced mice showed depression/anxiety-like behavior, which included shorter path length in the open field test and longer immobility time in the tail suspension test. L-SJE alleviated the depression-like behaviors. In the DSS-induced mice, reduced synaptic plasticity activated microglia, increased proinflammatory cytokines, decreased anti-inflammatory cytokine, and increased expression levels of Toll-like receptors-4, nuclear factor kappa-B, NOD-like receptors 3, apoptosis-associated speck-like protein, and Caspase-1 were observed, most of which were alleviated by SJE treatment. Furthermore, all the SJE groups could significantly enhance superoxide dismutase activity, while the L-SJE treatment decreased the contents of malondialdehyde, and the H-SJE treatment inhibited apoptosis. All these results showed that the SJE might serve as a nutritional agent for protecting the brain in ulcerative colitis mice.

Evaluation of Anti-depressant, Anti-anxiety and Muscle Relaxant Activity of Hydroalcoholic Extract of Aerva javanica Roots

Aims: To evaluate anti-depressant, anti-anxiety and muscle relaxant activity of hydroalcoholic extract of Aerva javanica roots in various experimental animal models. Study Design: Animal study. Place and Duration of Study: The study was conducted in Bilwal Medchem and Research Laboratory, Jaipur from July 2021-August 2021. Methodology: The root powder of Aerva javanica was extracted with hydroalcoholic solvent (70% ethanol). The hydroalcoholic extract at three doses 100 mg/kg, 200 mg/kg, and 400 mg/kg was checked for anti-depressant and skeletal muscle relaxant activity in the experimental animal models. To determine the anti-depressant activity tail suspension test, locomotor activity, open field test, and MAO inhibitor assay were done; to determine the anti-anxiety activity hole board test was used; and to determine the skeletal muscle relaxant activity rotarod test, grip strength test, and chimney test were done. Results: In the tail suspension test, the extract at 200 mg/kg and 400 mg/kg significantly reduced the duration of immobility compared to normal control (p<0.0001). The extract at dose 400 mg/kg significantly reduced MAO-A and MAO-B activity compared to the normal control group (p<0.01 and p<0.05, respectively). The extract at 200 mg/kg and 400 mg/kg were able to decrease locomotor activity in actophotomoter and increased time spent in centre square in open field test revealing the sedative effect of the extract. In hole board test, the extract at dose 400 mg/kg and 200 mg/kg significantly increased number of head dip count (p<0.0001 and p<0.001) respectively. In the rotarod test, the extract at dose 200 and 400 mg/kg decreased the time spent on the rotating rod (p<0.0001), compared to normal control. Similarly, in the grip strength test the extract at dose 200 and 400 mg/kg decreased the time spend on suspended wire revealing the skeletal muscle relaxant property of the test extract. Conclusion: Based on the result, it can be concluded that the extract exert anti-depressant, anti-anxiety and skeletal muscle relaxant like activity in the experimental rat which was hypothesized to be attributed to the flavonoids present in the hydroalcoholic root extract of Aerva javanica.

Analysis of Antidepressant-like Effects and Action Mechanisms of GSB-106, a Small Molecule, Affecting the TrkB Signaling

Induction of BDNF-TrkB signaling is associated with the action mechanisms of conventional and fast-acting antidepressants. GSB-106, developed as a small dimeric dipeptide mimetic of BDNF, was previously shown to produce antidepressant-like effects in the mouse Porsolt test, tail suspension test, Nomura water wheel test, in the chronic social defeat stress model and in the inflammation-induced model of depression. In the present study, we evaluated the effect of chronic per os administration of GSB-106 to Balb/c mice under unpredictable chronic mild stress (UCMS). It was observed for the first time that long term GSB-106 treatment (1 mg/kg, 26 days) during ongoing UCMS procedure ameliorated the depressive-like behaviors in mice as indicated by the Porsolt test. In addition, chronic per os administration of GSB-106 resulted in an increase in BDNF levels, which were found to be decreased in the prefrontal cortex and hippocampus of mice after UCMS. Furthermore, prolonged GSB-106 treatment was accompanied by an increase in the content of pTrkB706/707 in the prefrontal cortex and by a pronounced increase in the level of pTrkB816 in both studied brain structures of mice subjected to UCMS procedure. In summary, the present data show that chronic GSB-106 treatment produces an antidepressant-like effect in the unpredictable chronic mild stress model, which is likely to be associated with the regulation of the BDNF-TrkB signaling.

Strain-, Sex-, and Time-Dependent Antidepressant-like Effects of Cannabidiol

Cannabidiol (CBD) is a non-intoxicating compound extracted from Cannabis sativa, showing antidepressant-like effects in different rodent models. However, inconsistent results have been described depending on the species and the strain used to assess depressive-like behavior. Moreover, only a few studies investigated the effect of CBD in female rodents. Therefore, we aimed to (i) investigate the effects of CBD in two different strains of mice (Swiss and C57BL/6) and a rat model of depression based on selective breeding (Flinders Sensitive and Resistant Lines, FSL and FRL) subjected to tests predictive of antidepressant-like effects and (ii) investigate the influence of sex in the effects of CBD in both mice and rats. CBD induced an antidepressant-like effect in male Swiss but not in female Swiss or C57BL/6 mice in the tail suspension test (TST). In male FSL rats, CBD produced an antidepressant-like effect 1 h post injection. However, in female FSL, CBD induced a bimodal effect, increasing the immobility time at 1 h and decreasing it at 2 h. In conclusion, strain, sex, and administration time affect CBD’s behavioral response to rodents exposed to tests predictive of antidepressant effects.

Asperosaponin VI Ameliorates The CMS-Induced Depressive-Like Behaviors By Inducing A Neuroprotective Microglial Phenotype To Restore Hippocampal Synaptic Plasticity Via PPAR-γ Pathway

Background: The natural compound asperosaponin VI has shown potential as an antidepressant, but how it works is unclear. Here we explored its effects on mice exposed to chronic mild stress (CMS) and the underlying molecular pathways.Methods: Mice were exposed to CMS for three weeks followed by asperosaponin VI (40 mg/kg) or imipramine (20 mg/kg) for another three weeks. Depression-like behaviors were assessed in the forced swimming test, sucrose preference test, tail suspension test, open field test and novelty-suppressed feeding test. Microglial phenotype and synaptic plasticity were evaluated using immunofluorescence staining, real-time quantitative PCR and enzyme-linked immunosorbent assays in hippocampus of mice. In some experiments, stressed animals were treated with the PPAR-γ antagonist GW9622 to examine its involvement in the effects of asperosaponin VI.Results: Asperosaponin VI ameliorated depression-like behaviors of CMS mice based on all three behavioral tests, and this was associated with a switch of hippocampal microglia from a pro-inflammatory (iNOS+-Iba1+) to neuroprotective (Arg-1+-Iba1+) phenotype. The natural compound also promoted interactions between hippocampal microglia and neurons by enhancing CX3CL1/CX3CR1 and CD200/CD200R, and preserved synaptic plasticity based on PSD95 and CamKIIa levels. These effects of asperosaponin VI were blocked by GW9662. Conclusion: CMS in mice induces a proinflammatory microglial phenotype, disrupting neuron-microglia communication and synaptic function in hippocampus, ultimately leading to depression-like behaviors. Asperosaponin VI may ameliorate the effects of CMS by inducing microglia to adopt a PPAR-γ-dependent neuroprotective phenotype.

P2Y12 receptor as a new target for electroacupuncture relieving comorbidity of visceral pain and depression of inflammatory bowel disease

Background The P2Y12 receptor is a kind of purinoceptor that is engaged in platelet aggregation, and P2Y12 inhibitors have been used in clinical antithrombotic therapy. The P2Y12 receptor in microglia induces interleukin-1β (IL-1β) expression, which is a key mediator of depression in the brain. Although peripheral P2Y12 is involved in neuropathic pain, whether P2Y12 expression in the medial prefrontal cortex (mPFC) is associated with comorbidities of visceral pain and depression remains unclear. Accumulating evidence suggests that electroacupuncture (EA) is effective in treating inflammatory bowel disease (IBD), but its mechanism is unknown. This study aimed to determine whether P2Y12 expression in the mPFC is associated with comorbidities of visceral pain and depression in IBD and whether EA treats IBD by targeting the P2Y12 receptor. Methods We used 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced IBD mice. P2Y12 short hairpin RNA (shRNA) was stereotaxically injected into the bilateral mPFC. EA was performed on bilateral “Dachangshu” (BL25) acupoints once a day for 7 days. Von Frey filaments and colorectal distension were used to detect the mechanical pain threshold and visceral pain sensitivity. The sucrose preference test, tail suspension test and forced swimming test were used to evaluate depression in mice. Western blotting was used to test the expression of P2Y12 and IL-1β. Immunofluorescence staining was used to assess microglial activity. Results We found that IBD mice presented visceral pain and depression associated with increased P2Y12 expression in the mPFC. P2Y12 shRNA significantly attenuated visceral pain and depression in IBD mice. P2Y12 shRNA significantly downregulated IL-1β expression and inhibited the activation of microglia in the mPFC of IBD mice. Meanwhile, EA played a similar role of P2Y12 shRNA. EA significantly downregulated P2Y12 expression, weakened the activation of microglia, and then inhibited IL-1β expression in the mPFC, thus relieving visceral pain and depression in IBD mice. Conclusion The present study provided new ideas that the P2Y12 receptor in the mPFC could be a new target for the treatment of comorbid visceral pain and depression by EA. This may not only deepen our understanding of the analgesic and antidepressant mechanisms of EA but also promote the application of EA to treat IBD.