Thymoquinone lipid nanoparticles cut the Gordian knots of depression via neuroprotective BDNF and downregulation of neuro-inflammatory NF-κB, IL-6, and TNF-α in LPS treated rats

2021 ◽  
Vol 22 ◽  
Author(s):  
Mahtab Alam ◽  
Md Noushad Javed ◽  
Abul Kalam Najmi ◽  
Farhan Jalees Ahmad ◽  
Syed Sarim Imam ◽  
...  

Background: In over 300 million clinical cases, antidepressant drugs seem to provide only symptomatic relief and limited protection in life-threatening depressive events. Objective: To compare neuronal-signaling mechanism and neuroprotective roles of Thymoquinone (TQ) suspension and its SLN (TQSLN) against standard antidepressant drug fluoxetine. Results: As compared to fluoxetine, TQ reporteda significantly better docking score (-6.83 v/s -6.22) and a better lower free binding energy of (-34.715 Kcal/mol v/s -28.537 Kcal/mol). While poorly oral bioavailable and P-gp substrate TQ reported approximately 250% higher gut permeation if delivered as TQSLN formulation. In locomotor studies, as compared to TQS, TQSLN favored more prominent (p < 0.010) elevation in average time, horizontal-activity, average-velocity, and total-movement with reduced rest time LPS treated groups. However, in the tail suspension test, TQSLN significantly reduced immobility time (p<0.010). Similarly, In the modified force swimming test, TQSLN also significantly reduced immobility time (p<0.010), but swimming time (p<0.010) and climbing time (p<0.050) were significantly elevated. Conclusion: Despite the poor bioavailability of TQ, TQSLN potentially attenuates neuroinflammatory transmitters and favors BDNF to modulate depressive neurobehavioral states.

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Daehyuk Jang ◽  
Hyun-ju Lee ◽  
Kyungjun Lee ◽  
Kyu-Ri Kim ◽  
Ran Won ◽  
...  

Postmenopausal depression is closely associated with depletion of estrogen which modulates transmission of 5-HT, a key neurotransmitter that regulates stress-managing circuits in the brain. In this study, antidepressive efficacy of white ginseng (Panax gingseng Meyer, WG) was evaluated in stressed ovariectomized rats. Female Sprague Dawley rats were ovariectomized and repeatedly restraint stressed for 2 weeks (2h/day). Thirty minutes before restraint stress, rats were administered saline (control), WG 200 mg/kg (p.o.), WG 400 mg/kg (p.o.), or fluoxetine (PC, 10 mg/kg, i.p.). Tail suspension test (TST) and forced swimming test (FST) were performed to assess antidepressant effect of WG. After behavioral tests, levels of serum corticosterone (CORT) and hippocampal 5-HT were measured. Significant decrease of immobility time in TST and FST was shown in rats administered with PC or WG 400 compared to the control. WG200-treated rats showed remarkable reduction in immobility time of TST. PC, WG 200, or WG 400-administred group exhibited significant reduction of CORT compared to the control. PC or WG-treated rats exhibited remarkable increase in hippocampal 5-HT concentration compared to the control. Hippocampal 5-HT levels in WG groups were higher than those in the PC group. The present study demonstrated that WG had antidepressant efficacy in an animal model of menopausal depression. Treatment with WG enhanced hippocampal 5-HT level while suppressing depressive symptom and serum CORT level. These results provide evidence that WG plays an important role in activating serotonergic neurons in stressful situation, suggesting that WG might be a reliable natural alternative of antidepressant drugs to treat menopausal depression.


2021 ◽  
Vol 10 (2) ◽  
pp. 01-08
Author(s):  
Mr. Bablu Malviya ◽  
Mr. Narendra Patel ◽  
Dr.C.K. Tyagi ◽  
Dr. Prabhakar Budholiya

According to Biological Conservation Letter, more than 7,000 species of plants found in various ecosystems are said to be medicinal in the country. So, India is one of the world’s richest sources of medicinal and aromatic plants. Desmodium gangeticum is an important medicinal plant. It is commonly used in ayurvedic formulations for the treatment of various disorders. Phytochemical evaluations, pharmacogonostic evaluation, organoleptic characters, TLC profile was carried out to set them as diagnostic indices for the identification/validation of the raw material and standardization of the formulations. Preliminary phytochemical analysis showed the presence of active constituents which is necessary for the pharmacological activity. Organoleptic properties, phyto-chemical studies, powder analysis, showed the presence of adulteration in the powder. Majority of the antidepressant drugs improve depressive symptoms, but they exert multiple undesirable side effects. The search for more productive and well tolerated drugs is in progress. Phytochemical analysis of Desmodium gangeticum revealed the presence of alkaloids, phenols, flavonoids, Saponins, Steroids. Desmodium gangeticum is a well known medicinal plant as anti-inflammatory, antimicrobial and nephroprotective etc. It is a very good drug for urinogenital problems, hepatic problems, oxidative stress etc. The present study was depict to evaluate the antidepressant activity of hydroalcoholic extract of Desmodium gangeticum in mice. It was evaluated using the Tail Suspension Test (TST) and Forced Swimming Test (FST) in mice. Desmodium gangeticum (200 and 400 mg/kg) was administered orally in separate groups of Swiss albino mice weighing 20-25 for 14 days in TST and FST tests.. The Leaves extract of Desmodium gangeticum showed a dose dependant reduction in duration of immobility in mice. The dose of 400 mg/kg of Leaves extract of Desmodium gangeticum significantly reduced the immobility time of mice in both FST and TST. The effectual of extract was found to be similar to fluoxetine (20 mg mg/kg, po). It was found to be toxicologically safe with no deaths of mice when administered orally at the dose of 2000 mg/kg. From the current study, it can be concluded that the Leaves extract of Desmodium gangeticum possess dominant antidepressant activity as reveal by the TST and FST tests and is toxicologically safe.


Author(s):  
P. P. Mshelia ◽  
M. I. A. Saleh ◽  
O. O. Omodara ◽  
A. A. Madaki

Depression is a state of mood or energy level that includes lack of motivation, a sense of hopelessness and a loss of physical energy. The World Health Organization revealed that depression is one of the leading causes of ill health and disability worldwide. More than 300 million people are living with depression. Many of the currently available antidepressant drugs have proven to be effective but they are burdened with some disadvantages such as various adverse effects, problematic interactions and relatively low response. Therefore the need to utilize a natural agent in the management of depression is paramount. The aim of this study was to investigate the effects of chronic administration of extract of Allium sativum and Enriched environment in depression. 42 albino mice were used and divided into seven groups of five mice each. Group 1 was given distilled water; groups 2 and 3 received 200 mg/kg and 400 mg/kg of aqueous extract of Allium sativum respectively; while groups 4 and 5 were in addition to receiving 200 mg/kg and 400 mg/kg of the extract, housed in an enriched cage. Group 6 was only housed in an enriched cage and group 7 receives 10 mg/kg of imipramine. The experiment lasted for six weeks after which Force Swimming Test, Tail Suspension Test and Sucrose Preference test were conducted. The mice were sacrificed and their brain isolated, homogenized and centrifuged. The supernatant was used for biochemical assays (MDA, SOD, GPx, BDNF & TNF-α). The results showed that Allium sativum and Enriched Environment helped in mitigating depressive disorders. Therefore, conducive environment and garlic extract could be used in the management of depression.


2020 ◽  
Vol 16 (9) ◽  
pp. 1319-1327
Author(s):  
Ferdous Khan ◽  
Syed A. Kuddus ◽  
Md. H. Shohag ◽  
Hasan M. Reza ◽  
Murad Hossain

Background: An imbalance between pro-oxidants and antioxidants determines the level of oxidative stress which is implicated in the etiopathogenesis of various neuropsychiatric disorders including depression. Therefore, treatment with antioxidants could potentially improve the balance between pro-oxidants and antioxidants. Objective: The objective of this study was to evaluate the ability of astaxanthin, a potential antioxidant, to reduce reserpine-induced depression in BALB/c mice (Mus musculus). Methods: On the behavioral level, antidepressant property of astaxanthin (50 mg/kg, orally) on reserpine (2 mg/kg, subcutaneously) induced depressed mice was evaluated by Forced Swim Test (FST) and Tail Suspension Test (TST). In the biochemical level, the ability of astaxanthin to mitigate reserpine-induced oxidative stress was evaluated by the measurement of Malondialdehyde (MDA) and nitric oxide (NO) in brain, liver and plasma samples. On the other hand, the efficiency of astaxanthin to replenish glutathione depletion and antioxidant enzyme activity augmentation in the same samples were also investigated. Results: Astaxanthin was able to lower reserpine induced immobility time significantly (p<0.05) in FST and TST. Mice treated with astaxanthin showed significantly (p<0.05) low level of oxidative stress markers such as Malondialdehyde (MDA), Nitric Oxide (NO). Consistently, the level of reduced Glutathione (GSH), and the activity of Superoxide Dismutase (SOD) and catalase were augmented due to the oral administration of astaxanthin. Conclusion: This study suggests that astaxanthin reduces reserpine-induced oxidative stress and therefore might be effective in treating oxidative stress associated depression.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii86-ii86
Author(s):  
Dorothee Gramatzki ◽  
James Rogers ◽  
Marian Neidert ◽  
Caroline Hertler ◽  
Emilie Le Rhun ◽  
...  

Abstract PURPOSE Antidepressant drugs have shown anti-tumor activity in preclinical glioblastoma studies. Antidepressant drug use, as well as its association with survival, in glioblastoma patients has not been well characterized on a population level. METHODS Patient characteristics, including the frequency of antidepressant drug use, were assessed in a glioblastoma cohort diagnosed in a 10-year time-frame between 2005 and 2014 in the Canton of Zurich, Switzerland. Cox proportional hazards regression models were applied for multivariate analysis. Kaplan-Meier survival curves were used to estimate overall survival data and the log-rank test was performed for comparisons. RESULTS Four hundred four patients with isocitrate dehydrogenase (IDH) wildtype glioblastoma were included in this study. Sixty-five patients (16.1%) took antidepressant drugs at some point during the disease course. Patients were most commonly prescribed selective serotonin reuptake inhibitors at any time (N=46, 70.8%). Nineteen patients (29.2%) were on antidepressant drugs at the time of their tumor diagnosis. No differences were observed in overall survival between those patients who had taken antidepressants at some point in their disease course and those who had not (p=0.356). These data were confirmed in a multivariate analysis including age, Karnofsky performance status, gender, extent of resection, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and first-line treatment as cofounders (p=0.315). Also, there was no association of use of drugs modulating voltage-dependent potassium channels (citalopram; escitalopram) with survival (p=0.639). CONCLUSIONS This signal-seeking study does not support the hypothesis that antidepressants have antitumor efficacy in glioblastoma on a population level.


Author(s):  
Hossein Omidi-Ardali ◽  
Abolfazl Ghasemi Badi ◽  
Elham Saghaei ◽  
Hossein Amini-Khoei

AbstractObjectivesPrevious studies have suggested antidepressant properties for modafinil; however, the underlying mechanisms mediating the antidepressant effect of modafinil have not been well recognized in clinical and animal studies. Nitric oxide (NO) is involved in the pathophysiology of depression. We attempted to investigate the possible role of NO in the antidepressant-like effect of modafinil in mouse forced swimming test (FST) and tail suspension test (TST).MethodsThe antidepressant-like effect of modafinil (25, 50 and 75 mg/kg), alone and in combination with l-arginine, l-arg, (100 mg/kg) and NG-l-arginine methyl ester, l-NAME (5 mg/kg), was evaluated using FST and TST. Following behavioral tests, the hippocampi were dissected out to measure nitrite levels.ResultsFindings suggested that administration of modafinil at doses of 50 and 75 mg/kg significantly reduced immobility time in the FST and TST. Furthermore, administration of l-arg and l-NAME increased and decreased, respectively, the immobility time in the FST and TST. We showed that co-administration of a sub-effective dose of modafinil (25 mg/kg) plus l-NAME potentiated the antidepressant-like effect of the sub-effective dose of modafinil. In addition, co-treatment of an effective dose of modafinil (75 mg/kg) with l-arg attenuated the antidepressant-like effect of the effective dose of modafinil. We showed that the antidepressant-like effect of modafinil is associated with decreased nitrite levels in the hippocampus.ConclusionsOur findings for the first time support that the modulation of NO, partially at least, is involved in the antidepressant-like effect of modafinil in mouse FST and TST.


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Heba H El-Morsy ◽  
Wesam El-Bakly ◽  
Amany H Hasanin ◽  
May Hamza ◽  
M Abdel-Bary

Abstract Clinical observations recognized the co-existence and interactions of pain and depression a long time, ago. The aim of this work was to study the effect of ibuprofen and fluoxetine on BCGinduced depressive-like behaviour, on formalin-induced pain, as well as on mechanical allodynia after planter incision in mice. BCG induced a depressive behaviour that was seen in the forced swim test (FST) and the tail suspension test (TST). It also induced a decrease in pain-related behaviour in the formalin test, and an increase in the baseline in mechanical allodynia test compared to the control group. Fluoxetine (80 mg/L of drinking water) showed a significant decrease in the immobility time in the FST and TST and enhanced pain related behaviour in formalin test in the BCG-inoculated group. However, it did not affect the increase in the pain threshold in the planter incision allodynia model. Adding ibuprofen to drinking water (0.2 g/L of drinking water), reversed the depressive like behaviour induced by BCG and enhanced pain-related behaviour in formalin test, in both the total pain-related behaviour and phase 2. It also prevented the increase in the base line induced by BCG. On the other hand, the incisional pain model was not affected by BCG inoculation except at the 2-hour time point, where it showed hypoalgesia, as well.


Author(s):  
Chiranjeevi Bonda ◽  
Sudhir Pawar ◽  
Jaisen Lokhande

Background: The aim of the study was to evaluate the antidepressant effect of opioid analgesic tramadol using forced swim test and tail suspension test models.Methods: The antidepressant effect was assessed by recording the immobility time in Forced swim test (FST) and Tail suspension test (TST). The mice were randomly divided into five groups. Mice belonging to group I was given normal saline (0.1ml/kg) which acted as control. Group II received imipramine (15mg/kg) considered as the standard drug tramadol was given in graded dose (10, 20 and 40 mg/kg) to mice of groups III, IV, V respectively. All drugs were administered intraperitoneally for seven successive days; test was done on 7th day.Results: Tramadol and Imipramine showed antidepressant activity when compared to control. There is dose dependent increase in antidepressant activity of tramadol. The antidepressant activity of imipramine was significantly (P<0.05) more than tramadol at dose 10 and 20 mg/kg but antidepressant activity with tramadol 40mg/kg was comparable to imipramine treated mice.Conclusions: The results of this study indicated the presence of antidepressant activity of tramadol at 40mg/kg.


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