Antidepressant Effects Research Articles

A metabolomics approach reveals the pharmacological effects and mechanisms of Cistanche tubulosa stems and its combination with fluoxetine on depression in comorbid with sexual dysfunction

Ethnopharmacological relevanceThe dried succulent stems of Cistanche tubulosa (Schenk) Wight are utilized in traditional medicine for tonifying kidney yang, which have shown to be effective in alleviating depression-like behaviors or male sexual dysfunction, respectively. However, the pharmacological effects and mechanisms of C. tubulosa and its combinations in the treatment of depression in comorbid with sexual dysfunction remain unclear. Aim of the studyThis study aims to elucidate the pharmacological effects and mechanisms of C. tubulosa aqueous extract (CTE) and its combination with fluoxetine (FLX) on depression in comorbid with sexual dysfunction. Materials and methodsA mouse model of depression in comorbid with sexual dysfunction was created using the chronic unpredictable mild stress (CUMS) procedure. The therapeutic effects of CTE and its combination with FLX were assessed using depressive-like and mating behavior experiments, histopathological analysis, and hypothalamic-pituitary-gonadal (HPG) axis function evaluation. The mechanisms were explored by integrated serum and testicular metabolomics combined with network correlation analysis. ResultsCTE was confirmed to significantly improve depressive-like behaviors, reduce mating abilities, testicular histopathological damage, and HPG axis hormone secretion disorders in CUMS mice. Subsequently, mechanism exploration findings indicated that CTE might exert its effect by regulating potential efficacy-related biomarkers (isobutyrylglycine, citric acid, D-galactose) to improve certain metabolic pathways centered around steroid hormone biosynthesis and tricarboxylic acid (TCA) cycle. Furthermore, the combination of CTE and FLX exhibited stronger antidepressant effects than FLX alone, and ameliorated the exacerbated sexual dysfunction induced by FLX. These effects were achieved through the regulation of potential efficacy-related biomarkers (17α-hydroxypregnenolone, tetrahydrodeoxy-corticosterone, sphingosine, cortol, thymine, and L-histidine), thereby improving disorders in glycerophospholipid and histidine metabolism. ConclusionIn conclusion, the amelioration effects of CTE and its combination with FLX on depression in comorbid with sexual dysfunction were confirmed for the first time. This key mechanism may be achieved by modulating the levels of potential efficacy-related biomarkers, and then emphatically intervene in steroid hormone biosynthesis, TCA cycle, glycerophospholipid and histidine metabolism. The study offers a new perspective for the development and utilization of C. tubulosa.

Reveal the potent antidepressant effects of Zhi-Zi-Hou-Pu Decoction based on integrated network pharmacology and DDI analysis by deep learning

Reveal the potent antidepressant effects of Zhi-Zi-Hou-Pu Decoction based on integrated network pharmacology and DDI analysis by deep learning

Comparison of the Patient Health Questionnaire-9 and Quick Inventory of Depressive Symptomatology-Self Report in assessing the antidepressant effects of Transcranial Magnetic Stimulation: Sensitivity to change

BackgroundThe PHQ-9 and QIDS-SR are widely used assessment tools but have not been compared in sensitivity to the antidepressant effects of TMS. MethodsThe PHQ-9 and QIDS-SR were administered to 578 patients with MDD treated at a large TMS practice in Southern California. At baseline patients scored ≥ 10 on both instruments and received ≥ 36 TMS sessions (Mn=38.9, SD=5.3). Response was defined on each scale as ≥ 50 % reduction in scores and remission as a post-TMS score ≤ 5. ResultsBaseline symptom severity was greater on the PHQ-9 (Mn=19.1, SD=4.2) than QIDS-SR (Mn=18.2, SD=3.7), P < 0.0001. Both the change in scores from baseline to post-TMS [PHQ-9 (Mn=10.1, SD=6.8); QIDS-SR (Mn=8.4, SD=5.9), P < 0.0001] and percent change [PHQ-9 (Mn=52.1 %, SD=33.5); QIDS-SR (Mn=45.4 %, SD=30.2), P < 0.0001] were greater for the PHQ-9 than the QIDS. The remission rate was 10 % greater with the PHQ-9 than QIDS-SR (37.5 % vs. 27.9 %), P < 0.0001, while the nonresponse rate was greater on the QIDS-SR (49.7 % vs. 42.9 %), P < 0.0001. Effect sizes for differences in effectiveness among 3 TMS protocols were greater for the PHQ-9 than QIDS-SR. The PHQ-9 also showed greater internal consistency and higher loadings on a single depression severity factor. LimitationsThese are real world data, and the order of scale administration was unconstrained. ConclusionsThe PHQ-9 and QIDS-SR were highly correlated at baseline and following TMS. Nonetheless, the PHQ-9 was more sensitive to symptom change and appeared to assess more consistently a single dimension of depression severity.

Effect of antidepressants on ejaculation dysfunction in patients with depression and anxiety: A systematic review and network meta-analysis.

Antidepressants may lead to a series of sexual adverse effects (SAEs), among which ejaculation dysfunction (EjD) is often overlooked by clinicians. The purpose of the present network meta-analysis was to assist drug adjustment by comparing and ranking the incidence of EjD among various antidepressants. Relevant studies were retrieved from PubMed, Embase, Scopus, Web of Science, ClinicalTrials.gov, and other additional records. Eligible randomized controlled trials (RCTs) assessed the rate of EjD in patients with major depressive disorder (MDD) and anxiety disorder after taking anti-depressants. The incidences of EjD, erectile dysfunction (ED), decreased libido (DL), adverse events (AE), withdrawal due to adverse events (WDAE) and withdrawal due to lack of efficacy (WDLE) were pooled using odds ratio (OR) with their 95% confidence intervals (CI). The values of surface under the cumulative ranking curve (SUCRA) helped to rank the risk of each outcome in different antidepressants. Thirty RCTs comprising 18,157 patients were included. Results of all node-splitting analysis demonstrated no statistical inconsistency (all P>0.05). Clomipramine (OR 42.11, 95% CI [9.90, 179.08]), WS5570 (OR 28.99, 95% CI [1.48, 568.97]) and paroxetine (OR 18.63, 95% CI [9.33, 37.23]) had significant risk of EjD comparing to placebo. Additionally, duloxetine (OR 7.37, 95% CI [2.61, 20.78]), clomipramine (OR 5.29, 95% CI [1.72, 16.25]), paroxetine (OR 3.75, 95% CI [1.37, 10.26]) and escitalopram (OR 3.04, 95% CI [1.20, 7.71]) presented higher risk of ED comparing to placebo. Agomelatine, levomilnacipran, vortioxetine, trazodone, vilazodone, fluvoxamine and imipramine exhibited similar incidence of EjD with placebo (all P>0.05). Besides, trazodone, vilazodone and vortioxetine had the top-five SUCRA values in each of SAEs (EjD, ED and DL), and agomelatine might be alternative in EjD and DL. Considering about AE, WDAE and WDLE, vilazodone appeared to offer more satisfactory performance across all these aspects. For patients undergoing SAEs following the administration of antidepressants, trazodone, vortioxetine, vilazodone and agomelatine are alternative antidepressants.

Tofacitinib prevents depressive-like behaviors through decreased hippocampal microgliosis and increased BDNF levels in both LPS-induced and CSDS-induced mice.

Depressive disorders are a global mental health challenge that is closely linked to inflammation, especially in the post-COVID-19 era. The JAK-STAT pathway, which is primarily associated with inflammatory responses, is not fully characterized in the context of depressive disorders. Recently, a phase 3 retrospective cohort analysis heightened that the marketed JAK inhibitor tofacitinib is beyond immune diseases and has potential for preventing mood disorders. Inspired by these clinical facts, we investigated the role of the JAK-STAT signaling pathway in depression and comprehensively assessed the antidepressant effect of tofacitinib. We found that aberrant activation of the JAK-STAT pathway is highly conserved in the hippocampus of classical depressive mouse models: LPS-induced and chronic social defeat stress (CSDS)-induced depressive mice. Mechanistically, the JAK-STAT pathway mediates proinflammatory cytokine production and microgliosis, leading to synaptic defects in the hippocampus of both depressive models. Remarkably, the JAK inhibitor tofacitinib effectively reverses these phenomena, contributing to its antidepressant effect. These findings indicate that the JAK/STAT pathway could be implicated in depressive disorders, and suggest that the JAK inhibitor tofacitinib has a potential translational implication for preventing mood disorders far beyond its current indications.

The Interplay between MiR-134/BDNF and LKB1/AMPK/SIRT1 Accentuates the Antidepressant Efficacy of Empagliflozin in Ovariectomized Rats.

Major depressive disorder (MDD) is considered a major cause of suicide worldwide. As previous studies revealed that neuroinflammation is a significant factor in the etiology of MDD, this study proposed to unravel the possible antidepressant effect of Empagliflozin (EMPA) through targeting miRNA-134 (miR-134)/brain-derived neurotrophic factor (BDNF) and liver kinase B1 (LKB1)/adenosine 5'-monophosphate-activated protein kinase (AMPK)/silent information regulator 1 (SIRT1) axes in ovariectomized (OVX) female rats. Rats were assigned randomly to four groups: Sham operation (SO), OVX, OVX + EMPA (10 mg/kg/day, p.o.), and OVX + EMPA + Dorsomorphin (DORSO) (25 μg/day/rat, i.v.). Drugs were administered for 28 days after 2 weeks of surgery. EMPA debilitated OVX-induced depressive-like behavior by mitigating the immobility time in the tail suspension test and forced swimming test. Moreover, EMPA curtailed OVX-induced alterations of serum estradiol, hippocampal serotonin, miR-134 expression, as well as BDNF. EMPA also dwindled OVX-induced changes of hippocampal p-LKB1/LKB1, p-AMPK/AMPK, SIRT1, and inflammatory markers (nuclear factor-kappa-B, interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha). Additionally, the EMPA-treated group exhibited marked improvement in different brain regions' histopathology. However, DORSO coadministration reversed most of EMPA's beneficial effects. The current study displayed the modulatory role of EMPA on miR-134/BDNF and LKB1/AMPK/SIRT1 axes, thus offering a partial explanation of its antidepressant efficacy and proposing EMPA as a novel therapeutic avenue for MDD.

Exploring the Potential of Saffron as a Therapeutic Agent in Depression Treatment: A Comparative Review.

Depression is a significant mental health challenge globally. While traditional antidepressants are effective, they often have unwanted side effects. Saffron, a natural spice derived from Crocus sativus L., has emerged as a potential alternative therapy for depression. Researchers have found that its components such as crocin, crocetin, and safranal have been found to mitigate depressive symptoms through neurotransmitter regulation, anti-inflammatory effects, and neuroprotection. Clinical trials suggest that the effectiveness of saffron in treating mild to moderate depression is comparable to that of standard medications, and animal studies support these results, showing behavioral improvements with saffron treatment. Saffron is particularly appealing due to its safety and lower incidence of side effects, making it suitable for those sensitive to conventional drugs. Additionally, its antioxidant properties may offer further health benefits. However, challenges such as determining the appropriate dosage, prohibitive cost, and the limited availability of quality saffron need to be addressed. Most research on saffron's efficacy is short-term; thus, long-term studies are essential to understand its full therapeutic potential and ongoing antidepressant effects. While saffron is safe in terms of its culinary value, higher therapeutic doses require careful monitoring for drug interactions and side effects. In summary, saffron represents a promising direction in depression treatment, with benefits potentially matching those of standard treatments and a better safety profile. However, further research is necessary to establish clear guidelines for its use, optimize dosing, and assess long-term outcomes. Saffron offers a natural treatment path for depression, but its use must be controlled and supported by scientific evidence.

Molecular Docking Insights into Gatifloxacin Derivatives as Prospective Antidepressant Agents

ABSTRACT: The current focus in drug discovery aims to identify promising therapeutic candidates for further research. Depression, a significant public health issue, is closely linked to low serotonin levels. Researchers are investigating novel antidepressant agents through chemical modifications and protein analysis. The various derivatives are assessed for their antidepressant activity through in silico molecular docking simulations by using AutoDock and ADME analysis. Autodock includes formation of PDBQT files, docking of converted ligands and protein forms, formation of 9 different positions of docked molecules results into binding score, 2D image and 3D images of same one. Docking studies reveal molecular interactions between biological macromolecules (8FSB) and ligands, with strong protein-ligand interactions potentially inhibiting the reuptake of serotonin at the post-synaptic nerve, thereby increasing serotonin availability and exerting antidepressant effects. Gatifloxacin derivatives demonstrated higher binding affinities with 8FSB, Gati I (-11.4 kcal/mol), Gati II (-11.1 kcal/mol), Gati III (-8.2 kcal/mol), Gati IV (-7.9 kcal/mol), Gati V (-9.5 kcal/mol), and Gati VI (-9.7 kcal/mol), all exceeding gatifloxacin (-6.9 kcal/mol). These findings suggest that gatifloxacin derivatives may serve as potent antidepressants of drug discovery lies in the synergistic use of in vitro and in vivo studies, leveraging technological advancements to develop safer and more effective therapies. The findings related to gatifloxacin derivatives highlight the potential of these approaches in identifying novel antidepressants, paving the way for further research and clinical trials.

Synaptic basis of rapid antidepressant action.

The discovery of ketamine's rapid antidepressant action has generated intense interest in the field of neuropsychiatry. This discovery demonstrated that to alleviate the symptoms of depression, treatments do not need to elicit substantive alterations in neuronal circuitry or trigger neurogenesis, but rather drive synaptic plasticity mechanisms to compensate for the underlying pathophysiology. The possibility of a rapidly induced antidepressant effect makes therapeutic pursuit of fast-acting neuropsychiatric medications against mood disorders plausible. In the meantime, the accumulating clinical as well as preclinical observations raise critical questions on the nature of the specific synaptic plasticity events that mediate these rapid antidepressant effects. This work has triggered the current growing interest in alternative psychoactive compounds that are thought to have similar properties to ketamine and its action. This review covers our insight into these questions based on the work our group has conducted on this topic in the last decade.

In vitro and in vivo pharmacological evaluation of polygonum persicaria l.

The present study was designed to investigate the in vitro antioxidant, cytotoxic, anthelmintic and in vivo analgesic, anti-diarrheal, hypoglycemic and CNS anti-depressant properties of different solvent fractions of methanol extract of leaf and flower of Polygonum persicaria L., a notable medicinal plant in Bangladesh. The crude methanol extracts were partitioned separately to petroleum-ether, carbon tetrachloride, chloroform and aqueous fractions. In DPPH scavenging assay for antioxidant test, the aqueous fraction of flower extract showed maximum antioxidant activity with IC50 of 0.60 μg/ml. Most of the fractions revealed prominent lethality (LC50) against brine shrimp nauplii. The test samples also exhibited dose-dependent anthelmintic activity against Pheretima posthuma. The leaf extract and flower extract (200-and 400 mg/kg b.w.) can decrease the painful sensation in mice. Leaf extracts and flower extracts displayed 57.69 and 50% reduction of diarrhea induced by castor oil in mice, respectively. The plant samples exhibited hypoglycemic effect and CNS anti-depressant effect in mice. Based on the possibility of bioactivity, the plant can be thoroughly examined to determine its potential efficacy and to support its traditional uses. Bangladesh J. Bot. 53(3): 475-485, 2024 (September)

Effects of adjunctive esketamine on depression in elderly patients undergoing hip fracture surgery: a randomized controlled trial

BackgroundDepression is a prevalent perioperative psychiatric complication among elderly hip fracture patients. Esketamine has rapid and robust antidepressant effects. However, it is unknown whether it can alleviate depressive symptoms in elderly patients who undergo hip fracture surgery. This study aimed to explore whether the adjunctive esketamine in patient-controlled intravenous analgesia (PCIA) could improve depressive symptoms in elderly patients undergoing hip fracture surgery.MethodsA single-center, prospective, double-blind and randomized controlled clinical trial was carried out from July 2022 to August 2023 at the Wenzhou People’s Hospital among 90 patients, aged ≥ 65 years with hip fracture undergoing elective surgery. Participants were randomly allocated to either the esketamine group (group S) or the control group (group C). In Group S, patients were administered 0.5 mg/kg of esketamine as a PCIA adjuvant for 48 h, while the control group received saline. The primary outcome was the assessment of depressive symptoms using the Geriatric Depression Scale-15 (GDS-15) on postoperative day 2. The secondary outcomes were assessments of depressive symptoms on postoperative day 7 and postoperative day 30, serum levels of brain-derived neurotrophic factor (BDNF) and 5-hydroxytryptamine (5-HT), postoperative pain intensity, the number of effective PCIA presses, sufentanil consumption, and adverse events.ResultsThe prevalence and GDS-15 scores of depression were significantly lower in group S on postoperative day 2 (28.6% vs. 53.5%; 3.5 ± 1.8 vs. 4.3 ± 1.7, P < 0.05). In group S, the number of effective PCIA presses was significantly lower on postoperative day 2 than that in group C [2(1–4) vs. 1(0–2), P<0.05]. Higher levels of BDNF (23.8 ± 1.7 ng/mL vs. 25.3 ± 2.0 ng/mL, P < 0.05) and 5-HT (219.5 ± 19.5 ng/mL vs. 217.0 ± 22.2 ng/mL, P < 0.05) in the blood were observed on postoperative day 2 in group S.ConclusionIn elderly patients aged ≥ 65 years undergoing hip fracture surgery, the administration of adjunctive esketamine in PCIA could improve depressive symptoms and increase levels of BDNF and 5-HT in the blood.Trial registrationChinese Clinical Trial Registry, ChiCTR2200061956 (Date: 13/07/2022).

Mirtazapine blood levels and antidepressant response

Objective Therapeutic drug monitoring (TDM) is an important tool for treatment optimisation. Its usefulness has recently been demonstrated for some first-line antidepressants; however, few studies have been reported on the relationship between blood levels of mirtazapine and its antidepressant effects. The aim of this study was to investigate the association between blood concentration of mirtazapine and antidepressant response. Methods 59 outpatients treated with mirtazapine for depression were recruited and followed up for three months in a naturalistic setting. Hamilton Depression Rating Scale-21 (HAMD-21) was administered at baseline, month 1, and month 3 to assess antidepressant response. Mirtazapine serum concentration was measured at steady state. Linear regression analysis and nonlinear least-squares regression were used to estimate association between serum concentration of mirtazapine and antidepressant response. Results Our results showed no overall association between serum concentration of mirtazapine and symptom improvement at month 1 and month 3. A marginally significantly higher serum concentration of mirtazapine was found in responders vs non-responders at month 3. Conclusions The study suggests that serum concentration of mirtazapine is not strongly associated with the antidepressant efficacy of mirtazapine. This is probably attributed to its pharmacodynamic profile, even though higher blood levels seem to be marginally more effective.

Triagem in silico de compostos com atividade ansiolítica encontrados na espécie Magnolia obovata

Magnolia obovata, known as “Japanese cucumber”, is a deciduous tree of Asian origin, constituting a medicinal plant due to its anti-inflammatory, anxiolytic, antidepressant effects, among other central effects, already demonstrated in the literature. The objective of this study was to suggest the mechanisms of action for the effects on the central nervous system of the compounds identified in the species M. obovata, especially regarding the anxiolytic effect currently sought with the use of the plant. Nineteen compounds present in M. obovata were identified, with only 2 molecules (alpha-eudesmol and gamma-eudesmol) showing in silico pharmacokinetic and toxicological properties favorable to anxiolytic bioactivity. Such molecules inhibit acylcarnitine hydrolase and increase free acylcarnitine, possibly generating an anxiolytic effect. Pharmacophoric modeling of those molecules showed 6 interaction points with the 5 most potent known ligands of acylcarnitine hydrolase and such structural similarity is promising for acting on this target. There are advantages of the alternative mechanism of action of this compound in relation to current anxiolytics, which could be used to formulate new therapies in the treatment of anxiety disorders. The results obtained here open perspectives for tests in in vitro and in vivo models, aiming to confirm the results of the computational analyses.

Investigating the modulatory effects of lactoferrin on depressed rats through 16S rDNA gene sequencing and LC-MS metabolomics analysis.

Lactoferrin is a natural multifunctional glycoprotein with potential antidepressant-like effects. However, the mechanism of its antidepressant effect has not been explored from the perspective of gut flora metabolism. Therefore, we employed both 16S rDNA gene sequencing and LC-MS metabolomics analysis to investigate the regulatory effects and mechanisms of lactoferrin in a rat model of depression. After one week of acclimatization, twenty-four 7-week-old male Sprague-Dawley rats were randomly and equally assigned into three groups: the control group, the model group, and the lactoferrin intervention group. The control group rats were housed under standard conditions, while the rats in the model and lactoferrin intervention groups were individually housed and exposed to chronic unpredictable mild stress for 44days simultaneously. The lactoferrin intervention group was provided with water containing 2% lactoferrin (2g/100ml). Behavioural tests were conducted at week 7. Upon completion of the behavioral tests, the rats were anesthetized with isoflurane, humanely euthanized using a rat guillotine, and tissue samples were collected for further experiments. The results indicated that lactoferrin intervention led to an increase in sucrose solution consumption, horizontal movement distance, number of cross platforms, and residence time in the target quadrant. Additionally, it resulted in an increase in jejunal tight junction protein ZO-1 expression and a suppression of serum expression of inflammatory factors, Lipopolysaccharide and Diamine oxidase. In summary, lactoferrin can regulate the metabolic disorder of intestinal flora, reduce intestinal permeability, and further regulate the metabolic balance of hippocampal tissues through the microbiota-gut-brain axis. This process ultimately alleviates the depression-like behavior in rats.

The Effectiveness of Ketamine Treatment on Depression

As the diagnosis rate of depression continues to rise, effective treatment options for this condition have become one of the most researched areas in the field. Earlier antidepressants were primarily developed based on mechanisms that involve regulating imbalanced neurotransmitters. For example, the widely known Selective Serotonin Reuptake Inhibitors (SSRIs) and various tricyclic antidepressants work by adjusting the concentration of different neurotransmitters, such as dopamine and norepinephrine, in the synaptic cleft to alleviate depressive symptoms. Additionally, many therapeutic approaches have been developed and applied based on the widely accepted hormone hypothesis and neurotrophic factor hypothesis. Ketamine, a drug traditionally used as an anesthetic, has recently been discovered to possess antidepressant properties. Its efficacy and underlying neuroscientific mechanisms are currently under investigation. Unlike earlier antidepressants, Ketamine produces significant antidepressant effects within a short time after administration. Multiple studies have suggested that Ketamine's rapid and effective therapeutic results may be based on entirely new antidepressant mechanisms and targets that have yet to be fully understood. This provides a new solution for the treatment of treatment-resistant depression and offers new hope to patients who have tried various treatments without success. In this literature review, Ketamine's therapeutic effects and its underlying mechanisms will be thoroughly examined. The content will be divided into three sections: significant antidepressant effects, underlying principles and mechanisms, and factors relevant to the improvement of Ketamine therapy.

PET imaging assist investigation of HDAC6 expression change in MDD and evaluating antidepressant efficacy of a newly developed HDAC6 inhibitor

The histone deacetylase 6 (HDAC6) is closely related to the pathogenesis of depression in epigenetic regulation. However, it remains unclear how HDAC6 expression changes in depression pathophysiology and whether it is a target for antidepressant treatment. Herein, we investigate the expression change of HDAC6 in major depressive disorder (MDD) and evaluate the efficacy of a novel HDAC6 inhibitor, PB200, using positron emission tomography (PET) imaging. PET imaging studies with an HDAC6 PET probe [18F]Bavarostat allied with in vitro experiments demonstrated significantly increased HDAC6 expression in the brains of MDD mice. To investigate if pharmacological inhibition of HDAC6 can exert antidepressant effects, a series of naphthyridine-based HDAC6 inhibitors were designed and synthesized, among which PB200 demonstrated high selectivity and inhibitory activity against HDAC6, favorable metabolic stability, and excellent brain uptake. Moreover, PB200 exhibited significant antidepressant effects by restoring abnormal HDAC6 expression level and alleviating neuroinflammation. These results imply that targeting HDAC6 shows promise as a therapeutic strategy for depression, and PB200 is a potential therapeutic option for treating MDD.

Unveiling the therapeutic potentialities and chemical characterization of methanolic Merremia vitifolia (Burm.f) Hallier f. stem extract: A Multi-faceted investigation via in vitro, in vivo, and in silico approaches

Current study focused on Merremia vitifolia an ethnomedicinal plant, aiming to explore its medicinal properties comprehensively. Through qualitative and quantitative analysis, the study investigated the phytochemical components of M. vitifolia stem extract and assessed its antioxidant, anti-inflammatory, analgesic, antidepressant, anxiolytic, locomotor, and antidiarrheal activities. The evaluation involved a combination of in vitro, in vivo, and in silico approaches.In-vitro antioxidant activity was determined using the DPPH scavenging assay, while anti-inflammatory activity was assessed via a protein denaturation assay. In-vivo experiments included tests for antidepressant effects (FST, TST), anxiolytic effects (EPM, HBT), locomotor effects (OFT, HCT), and analgesic activity (formalin-induced licking test and acetic acid-induced writhing test). Additionally, the antidiarrheal effect was evaluated through castor oil-induced diarrhea and gastrointestinal motility tests. Fifteen bioactive compounds were identified based on their biological activities from GC/MS data and subjected to in silico molecular docking; ADME/T profiling and pass prediction.MEMVS had an IC50 value of 74.97 μg/mL and MEMVS elicited 77.17 ± 0.39 % inhibition protein denaturation compared to standard (87.23 ± 0.30 %) at 500 μg/mL. In addition, MEMVS induced a dose-dependent reduction in analgesic, neuropharmacological assay, inhibition in diarrheal feces count, and intestinal motility with a significant value (aP< 0.001). In computer-aided investigation, all compounds adhere to Lipinski's rule of five and demonstrate highest binding affinity to isolates compared to standard drugs, confirming laboratory findings.Research findings suggest that MEMVS holds promising potential, as a multifaceted therapeutic agent, exhibiting antioxidant, analgesic, anti-inflammatory, anti-diarrheal and neuropharmacological properties. However, further investigation is needed to fully harness its medicinal benefits.

Structural characteristics and potential antidepressant mechanism of a water-insoluble β-1,3-glucan from an edible fungus Wolfiporia cocos

A water-insoluble β-1,3-glucan (Wβ) with a molecular weight of 8.12 × 104 Da was extracted from an edible fungus Wolfiporia cocos. Its backbone was composed of 1,3-β-linked Glcp branched at the C-2, C-4, and C-6 positions, connecting more 1,3-β-linked Glcp with a triple helical structure. Wβ effectively ameliorated depressive symptoms, abnormality of neurotransmitters and inflammatory factors in chronic unpredictable mild stress (CUMS)-induced rats. Wβ also altered the composition of gut microbiota, especially Romboutsia, norank_f_Muribaculaceae and Ruminococcus. Integration of untargeted and targeted metabolomics and Western blotting analysis suggested that the short-chain fatty acids (SCFAs) and tryptophan metabolites were the most important metabolites involved in Wβ mediation. Wβ significantly modulated the levels of 7 SCFAs and 7 tryptophan metabolites, as well as the protein expression of two related enzymes (indoleamine-2,3-dioxygenase: IDO; kynurenine-3-monooxygenase: KMO). Our results suggest that Wβ exerts its antidepressant effect by influencing neurotransmitters and inflammatory factors through interactions between the gut microbiota, SCFA and tryptophan metabolites. The findings offer new insights into water-insoluble polysaccharides, especially β-glucan in structure analysis and utilization, and provide evidence that Wβ, a novel glucan from the often-discarded water-insoluble part of Wolfiporia cocos, has potential application in antidepressant health products.

Alpinia zerumbet Anxiolytic and Antidepressant Effects: A Literature Review

Studies demonstrated that many elderly individuals suffer from depressive and anxiety disorders. The drugs used to treat these disorders cause adverse effects such as sedation, gastrointestinal discomfort, and locomotor deficits, which are often responsible for treatment abandonment. Literature data also describe that older people may be refractory to pharmacological treatments used to combat depressive and anxiety disorders, which is potentially worrying due to the suicide risk associated with these conditions. Previous research reported the medicinal plant's beneficial potential in psychiatric disease treatment due to its antioxidant, anti-inflammatory, and antiapoptotic actions. This paper reviews the Alpinia zerumbet actions, a medicinal plant with antidepressant and anxiolytic effects, through increases in noradrenergic neurotransmission and decreases oxidative stress on the central nervous system by increasing antioxidant activity. Moreover, Alpinia zerumbet also causes a reduction in IL-6 and elevates BDNF levels in the hippocampus, contributing to its antidepressant, anxiolytic, and anti-inflammatory actions. The adverse effects reduction, combined with the fact that there is no toxicity when ingested by humans and increased longevity, suggests that this medicinal plant is promising for older individuals treatment who suffer from depression and anxiety.

Antidiabetic activity and Safety evaluation of Triticum aestivum (wheatgrass) extract in Alloxan-induced diabetic rats model.

Triticum aestivum (wheatgrasses) extract was studied for antidiabetic activity using alloxan-induced diabetes mellitus in rats. Triticum aestivum at 50, 100, and 200 mg/kg showed significant antidiabetic activity; it effected profound reductions in blood glucose over 28 days, especially the higher doses of 100 and 200 mg/kg, which were more effective than Glibenclamide. At 2000 mg/kg, the extract did not lower the blood glucose of normoglycemic rats- an indication of its safety and lack of hypoglycemic responses under non-diabetic conditions. It would appear that the antidiabetic activity of Triticum aestivum is through the protection and regeneration of beta cells that enhance insulin secretion, which in turn increases the utilization of glucose and normalizes carbohydrate, fat, and protein metabolism. This gradual lowering of blood glucose levels brought on by Triticum aestivum is clinically highly desired. The elicited antidepressant effect of Triticum aestivum was very likely due to its antioxidant effects and beta-cell regeneration activity. Thus, Triticum aestivum can meet the demand for a nontoxic, safe alternative to orthodox antidiabetic agents. Triticum aestivum, antidiabetic activity, alloxan-induced diabetes, insulin secretion, beta-cell regeneration, glucose metabolism, safety, and Glibenclamide.