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

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.

Emodin Prevented Depression in Chronic Unpredicted Mild Stress-Exposed Rats by Targeting miR-139-5p/5-Lipoxygenase

BackgroundThe use of medicinal plant ingredients is one of the goals of developing potential drugs for treating depression. Compelling evidence suggests that anti-inflammatory medicines may block the occurrence of depression. We studied the effect of a natural compound, emodin, on the development of psychosocial stress-induced depression and the underlying mechanisms.MethodsChronic unpredicted mild stress (CUMS) for 7 weeks was performed to replicate psychosocial stress in rats. The sucrose preference test, force swimming test, and open field test were used to evaluate their behaviors. The differentially expressed proteins in the hippocampus were analyzed using proteomics. Nissl staining and Golgi staining were used to detect the loss of neurons and synapses, immunohistochemical staining was used to detect the activation of microglia, and the enzyme-linked immunosorbent assay was used to detect the levels of pro-inflammatory cytokines. Western blotting, immunofluorescence, and quantitative polymerase chain reaction were also performed.ResultsHippocampal inflammation with up-regulated 5-lipoxygenase (5-LO) was observed in the depressed rats after CUMS exposure. The upregulation of 5-LO was caused by decreased miR-139-5p. To observe the effect of emodin, we screened out depression-susceptible (DeS) rats during CUMS and treated them with emodin (80 mg/kg/day). Two weeks later, emodin prevented the depression behaviors in DeS rats along with a series of pathological changes in their hippocampi, such as loss of neurons and spines, microglial activation, increased interleukin-1β and tumor necrosis factor-α, and the activation of 5-LO. Furthermore, we demonstrated that emodin inhibited its excess inflammatory response, possibly by targeting miR-139-5p/5-LO and modulating glycogen synthase kinase 3β and nuclear factor erythroid 2-related factor 2.ConclusionThese results provide important evidence that emodin may be a candidate agent for the treatment of depression and established a key role of miR-139-5p/5-LO in the inflammation of depression.

Hippocampal Glycerol-3-Phosphate Acyltransferases 4 and BDNF in the Progress of Obesity-Induced Depression

BackgroundObesity has been reported to lead to increased incidence of depression. Glycerol-3-phosphate acyltransferases 4 (GPAT4) is involved in triacylglycerol synthesis and plays an important role in the occurrence of obesity. GPAT4 is the only one of GPAT family expressed in the brain. The aim of this study is to investigate if central GPAT4 is associated with obesity-related depression and its underlying mechanism.ResultsA high-fat diet resulted in increased body weight and blood lipid. HFD induced depression like behavior in the force swimming test, tail suspension test and sucrose preference test. HFD significantly up-regulated the expression of GPAT4 in hippocampus, IL-1β, IL-6, TNF-α and NF-κB, accompanied with down-regulation of BDNF expression in hippocampus and ventromedical hypothalamus, which was attributed to AMP-activated protein kinase (AMPK) and cAMP-response element binding protein (CREB).ConclusionOur findings suggest that hippocampal GPAT4 may participate in HFD induced depression through AMPK/CREB/BDNF pathway, which provides insights into a clinical target for obesity-associated depression intervention.

Ameliorative Effects of Enriched Environment and Chronic Administration of Aqueous-methanol Extract of Garlic (Allium sativum) on Mice Models of Depression

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.

Emodin Prevented Depression in Chronic Unpredicted Mild Stress Exposured Rats by Targeting MiR139-5p/5-Lipoxygenase

Background: Using ingredients of medicinal plants is one of the goals of developing potential drugs for treating depression. Compelling evidences suggested anti-inflammation might block the occurrence of depression. Here, the effect of a natural compound, emodin, on the developing of psychosocial stress-induced depression and the underlying mechanism were studied.Methods: 7 weeks’ chronic unpredicted mild stress (CUMS) were performed to replicate psychosocial stress in rats, and sucrose preference test, force swimming test and open field test were used to evaluate their behaviors. The differentially expressed proteins in hippocampus were analyzed by proteomics. Nissl staining and Golgi staining were used to detect the losses of neurons and synapses, immunohistochemical staining was used to detect the activation of microglia, and ELISA was used to detect the levels of pro-inflammatory cytokines. Western blotting, immunofluorescence and quantitative PCR were also included.Results: Hippocampal inflammation with up-regulated 5-lipoxygenase (5-LO) was observed in the depressed rats after CUMS exposure. And the up-regulation of 5-LO was proved to be caused by the decrease of miR139-5p. To observe the effect of emodin, we screened out depression susceptible (DeS) rats during CUMS and treated them with emodin (80mg/kg/day). 2 weeks later, emodin obviously prevented the depression behaviors of DeS rats and a series of pathological changes in their hippocampi, such as losses of neurons and spines, microglia activation, increased interleukin-1b and tumor necrosis factor-a, and the activation of 5-LO. Furtherly, we demonstrated that emodin inhibited its excess inflammatory responses possibly by targeting miR139-5p/5-LO and modulating the downstream glycogen synthase kinase 3β and nuclear factor erythroid 2-related factor 2. Conclusions: These results provided an important evidence that emodin may be a candidate agent for the treatment of depression and established a key role of miR139-5p/5-LO in the inflammation of depression.

Antidepressant Activity of Some Fractions of The Basil Leaves [Ocimum Basilicum (L)] on The Swiss Webster Male Mice

Objectives : Determine the antidepressant activity of some fractions of the leaves of Ocimum basilicum L Methods : The experimental methods are using Force Swimming Test and Tail Suspension Test. The experiment was divided into seven groups. Negative control group (CMC 1 %), Positive control group (fluoxetine 0,052 mg/20 g BW of mice), test I group (fraction of n-hexane 50 mg/Kg BW), test II group (fraction of ethyl acetate 50 mg/Kg BW), test III group (fraction of ethanol 50 mg/Kg BW), test IV group (combination of cyproheptadine 0,0208 mg/20 g BW of mice and fluoxetine 0,052 mg/20 g BW of mice) and test V group (combination of cyproheptadine 0,0208 mg/20 g BW of mice and fraction of ethyl acetate 50 mg/Kg BW). Result : The Force Swimming Test and Tail Suspension Test showed the same result that ethyl acetate fraction was given significant difference (p<0,05) in immobilization time reduction compared to negative control and has a better immobility reduction time than other groups. Added on cyproheptadine to fluoxetine and ethyl acetate fraction groups showed an increased in immobilization time compared to fluoxetine and ethyl acetate fraction alone. Conclusion : Ethyl acetate fraction showed better antidepressant activity than another fraction through the role of serotonin.

Evaluation of antistress activity of Cassia auriculata seed extract

Objective: The present study was designed to investigate the anti-stress activity of Cassia auriculata ethanolic seed extract in mice. Methodology: The anti-stress effect was evaluated by using Elevated plus maze (EPM), Force swimming test (FST) and Tail suspension test (TST). The ECS at a doses (250,500 and 1000 mg/kg p.o.) and standard (diazepam 2 mg/kg i.p and fluoxetine 20 mg/kg i.p) was administered. Results: The extract showed the increased in the number of entries and time spent in open arm in Elevated plus maze and decreased in the immobility time in both Force swimming test and Tail suspension test. Conclusion: The effect of ESC on animal behavior was concordant with a significant regulation of GABA and stress hormones. Therefore, this study was attempted to demonstrate the preventive potential of ECS against stress disorders at in vivo levels