scholarly journals Zhile Capsule Exerts Antidepressant-Like Effects through Upregulation of the BDNF Signaling Pathway and Neuroprotection

2019 ◽  
Vol 20 (1) ◽  
pp. 195 ◽  
Author(s):  
Jiawei Wu ◽  
Tingting Zhang ◽  
Luping Yu ◽  
Shuai Huang ◽  
Yu Yang ◽  
...  
Keyword(s):  
Forced Swim Test ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Underlying Mechanism ◽  
Enzyme Linked Immunosorbent Assay ◽  
Common Disease ◽  
Therapeutic Effects ◽  
Mild Stress ◽  
Neuroprotective Effects ◽  
Sucrose Preference Test

Major depressive disorder is now becoming a common disease in daily life, and most patients do not have satisfactory treatment outcomes. We herein evaluated the therapeutic effects of Zhile capsule and clarified the molecular mechanism. A rat model of chronic unpredictable mild stress-induced depression was established to assess the antidepressant-like effects of Zhile by using the sucrose preference test, open field test, forced swim test, tail suspension test and HPLC. Systems pharmacology was then performed to unravel the underlying mechanism which was confirmed by western blot, enzyme-linked immunosorbent assay, and qPCR. Zhile alleviated depression-like behaviors by upregulating the cAMP-CREB-BDNF (brain-derived neurotrophic factor) axis to exert neuroprotective effects. It may be beneficial to depressive patients in clinical practice.

scholarly journals The Antidepressant-Like Effects of Shen Yuan in a Chronic Unpredictable Mild Stress Rat Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Ning Jiang ◽  
Haixia Wang ◽  
Hong Huang ◽  
Jingwei Lv ◽  
Guirong Zeng ◽  
...  
Keyword(s):  
Panax Ginseng ◽  
Forced Swim Test ◽  
Preference Test ◽  
Underlying Mechanism ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Oxidative Markers ◽  
Immobility Time ◽  
Polygala Tenuifolia ◽  
Sucrose Preference Test

Depression is a common yet severe neuropsychiatric condition that causes imposes considerable personal, economic, and social burdens worldwide. Medicinal plant species (e.g., Panax ginseng and Polygala tenuifolia) demonstrate potent antidepressant-like effects with less toxicity and other side effects. Shen yuan prescription (SY), composed of Panax ginseng (GT) and Polygala tenuifolia (YT). The present study aimed to elucidate the effects of SY treatment on chronic unpredictable mild stress (CUMS) rats and study the underlying mechanism. Our results indicated that SY (67.5, 135, or 270 mg/kg) significantly reverses the depressive-like behaviors in rats with a 5-week CUMS exposure, as demonstrated by increased sucrose consumption in the sucrose preference test, and decreased immobility time in the tail suspension and forced swim test. Moreover, SY altered serum corticosterone levels, pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α), and oxidative markers (SOD, CAT, and MDA), and increased the levels of hippocampal neurotransmitters (5-HT, DA, and NE) in rats exposed to CUMS. Furthermore, rats treated with SY showed a reduction in the protein expression of BDNF, p-TrkB, p-Akt, and p-mTOR proteins induced by CUMS exposure in the hippocampus. In conclusion, SY prevented depressive-like behaviors in CUMS-exposed rats by preventing hypothalamus-pituitary-adrenal axis dysfunction, decreasing the levels of the neurotransmitters, minimizing oxidative stress, suppressing neuroinflammation, and activating the PI3K/Akt/mTOR-mediated BDNF/TrkB pathway, all of which are the key players in the pathological basis of depression.

scholarly journals Buyang Huanwu Decoction Ameliorates Poststroke Depression via Promoting Neurotrophic Pathway Mediated Neuroprotection and Neurogenesis

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Lin Luo ◽  
Shuhua Deng ◽  
Jian Yi ◽  
Sainan Zhou ◽  
Yan She ◽  
...  
Keyword(s):  
Forced Swim Test ◽  
Chronic Mild Stress ◽  
Preference Test ◽  
Underlying Mechanism ◽  
Artery Occlusion ◽  
Mild Stress ◽  
Poststroke Depression ◽  
Buyang Huanwu Decoction ◽  
Sucrose Preference Test ◽  
Cerebral Artery Occlusion

Objective.The aim of the present research is to investigate the therapeutic effect of Buyang Huanwu Decoction (BHD) in poststroke depression (PSD) animal model and illustrate its underlying mechanism via promoting neurotrophic pathway mediated neuroprotection and neurogenesis.Methods.To induce PSD rat model, isolation housed rats that received middle cerebral artery occlusion (MCAO) surgery successively suffered from chronic mild stress (CMS) treatment for consecutive twenty-one days. Meanwhile, rats were correspondingly given vehicle, BHD, and fluoxetine. Then, neurologic function was scored and depressive-like behaviors were assessed by sucrose preference test, locomotor activity, novelty-suppressed feeding test, and forced swim test. Thereafter, the neuroprotection and neurogenesis related molecular markers and signaling were detected.Results.We firstly observed a significant neurological function recovery and antidepressants effect of BHD after MCAO together with CMS treatment. Our study also found that treatment with BHD and fluoxetine can significantly rescue neurons from apoptosis and promote neurogenesis in the CA3 and DG regions in the hippocampus. Notably, BHD and fluoxetine treatment can activate BDNF/ERK/CREB signaling.Conclusion.The results suggest that BHD is a promising candidate for treating PSD. Its curative effects can be attributed to neurotrophic pathway mediated neuroprotection and neurogenesis.

Effect of (4a) a novel 5-HT3 receptor antagonist on chronic unpredictable mild stress induced depressive-like behavior in mice: an approach using behavioral tests battery

2015 ◽  
Vol 26 (1) ◽  
Author(s):  
Yeshwant Kurhe ◽  
Radhakrishnan Mahesh ◽  
Deepali Gupta ◽  
Devadoss Thangaraj
Keyword(s):  
Lipid Peroxidation ◽  
Forced Swim Test ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Brain Homogenate ◽  
Therapeutic Interventions ◽  
Mild Stress ◽  
Behavioral Alterations ◽  
Biochemical Alterations ◽  
Immobility Time

AbstractThe inconsistent therapeutic outcome necessitates designing and identifying novel therapeutic interventions for depression. Hence, the present study deals with the investigation of antidepressant-like effects of a novel 5-HTAnimals were subjected to different stressors for a period of 28 days. On day 15 after the subsequent stress procedure, mice were administered with (4a) (2 and 4 mg/kg p.o.), escitalopram (10 mg/kg p.o.), or vehicle (10 mL/kg p.o.) until day 28 along with the CUMS. Thereafter, behavioral battery tests like locomotor score, sucrose preference test, forced swim test (FST), tail suspension test (TST), and elevated plus maze (EPM) were performed. Biochemical assays like lipid peroxidation, nitrite levels, reduced glutathione (GSH), catalase, and superoxide dismutase (SOD) were estimated in the mice brain homogenate.(4a) Dose dependently attenuated the behavioral alterations by increasing the sucrose consumption, reducing the immobility time in FST and TST, increasing the open arm number of entries and time in EPM. Furthermore, biochemical alterations were reversed by (4a) as examined by reduced lipid peroxidation and nitrite levels and elevated antioxidant enzyme levels like GSH, catalase and SOD.(4a) exhibits antidepressant potential by reversing the CUMS induced behavioral and biochemical changes in mice.

scholarly journals ANTIDEPRESSANT-LIKE ACTIVITY OF TRANS-ANETHOLE IN UNSTRESSED MICE AND STRESSED MICE

2019 ◽  
pp. 121-127
Author(s):  
DINESH DHINGRA ◽  
SUDHA
Keyword(s):  
Preference Test ◽  
Tail Suspension Test ◽  
Plasma Corticosterone ◽  
Monoamine Oxidase A ◽  
Sucrose Preference ◽  
Mild Stress ◽  
Male Mice ◽  
Mao A ◽  
Sucrose Preference Test ◽  
Plasma Nitrite

Objectives: The present study was undertaken to investigate the antidepressant potential of trans-anethole in unstressed and stressed male mice. Methods: Swiss albino male mice were exposed to chronic unpredictable mild stress for 21 successive days. Simultaneously, trans-anethole (12.5 mg/kg, 25 mg/kg, and 50 mg/kg) and fluoxetine (20 mg/kg) per se were administered for 21 successive days to separate groups of unstressed and stressed mice. The effect of drugs on depressive-like behavior of mice was tested by tail suspension test (TST) and sucrose preference test. Results: Trans-anethole (25 mg/kg) and fluoxetine significantly decreased the immobility period of unstressed and stressed mice in TST as compared to their respective control. These drugs significantly restored the reduced sucrose preference (%) in stressed mice. Trans-anethole did not show any significant effect on locomotor activity of mice. Antidepressant-like activity of trans-anethole (25 mg/kg) was found to be comparable to fluoxetine. Trans-anethole and fluoxetine significantly inhibited brain monoamine oxidase-A (MAO-A) activity, decreased plasma nitrite, brain malondialdehyde, and increased brain reduced glutathione levels and catalase activity in unstressed and stressed mice. The drugs significantly reversed stress-induced increase in plasma corticosterone levels. Conclusion: Trans-anethole produced significant antidepressant-like activity in unstressed and stressed mice, possibly through inhibition of brain MAO-A activity and alleviation of oxidative stress. Reversal of stress-induced increase in plasma corticosterone levels might also be responsible for antidepressant-like activity of trans-anethole in stressed mice.

scholarly journals Crassifoside H ameliorates depressant behavior in chronic unpredictable mild stress rats by improving HPA axis dysfunction and inhibiting inflammation in hippocampus

2020 ◽  
Vol 19 (8) ◽  
pp. 1693-1699
Author(s):  
Huina Li ◽  
Kefan Wu ◽  
Yue Zhang ◽  
Ning Li ◽  
Kaijin Wang
Keyword(s):  
Hpa Axis ◽  
Mechanism Of Action ◽  
Therapeutic Potential ◽  
Preference Test ◽  
Antidepressant Effect ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Tnf Α ◽  
Sucrose Preference Test

Purpose: To investigate the antidepressant mechanism of action of Crassifoside H (CH) from the rhizomes of Curculigo glabrescens (Hypoxidaceae) in chronic unpredictable mild stress (CUMS)-induced rats.Methods: CUMS-induced rat depressant model was established. Behavioral tests, viz, sucrose preference test (SPT), open field test (OFT) and forced swimming test (FST) were applied to assess the antidepressant effect of CH. Enzyme linked immunosorbent assay (ELISA) was used to assess thelevels of corticosterone (CORT), TNF-α and IL-1β in serum. Protein expressions of TNF-α, IL-1β and NLRP3 in rat hippocampus were determined by Western blot.Results: Crassifoside H significantly ameliorated CUMS-induced depressant-like behavior as the serum CORT level of CUMS rats. CH remarkably decreased TNF-α and IL-1β levels in serum and hippocampus of CUMS rats. Moreover, Crassifoside H significantly inhibited NLRP3 activation inhippocampus.Conclusion: The findings demonstrate that Crassifoside H has antidepressant effect on CUMS rats. The mechanism of action of CH may be at least partly due to the improvement of hypothalamic-pituitaryadrenal (HPA) axis dysfunction by decreasing serum CORT. These findings suggest that Crassifoside H has a therapeutic potential for the management of depression. Keywords: Crassifoside H, Antidepression, Curculigo glabrescens, Hypoxidaceae, Hypothalamicpituitary- adrenal axis, Inflammation, Corticosterone

scholarly journals Jianpi Jieyu Decoction, An Empirical Herbal Formula, Exerts Psychotropic Effects in Association With Modulation of Gut Microbial Diversity and GABA Activity

2021 ◽  
Vol 12 ◽  
Author(s):  
Lanying Liu ◽  
Zhilu Zou ◽  
Jiangwei Yang ◽  
Xiaoqi Li ◽  
Boran Zhu ◽  
...  
Keyword(s):  
Serum Level ◽  
Gut Microbiota ◽  
Forced Swim Test ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Antidepressant Effect ◽  
Mild Stress ◽  
Gamma Aminobutyric Acid ◽  
Object Recognition Test ◽  
Microbial Distribution

Background: Recent studies suggest that gut microbiota was associated with the bidirectional gut-brain axis which could modulate neuropsychological functions of the central nervous system. Gut microbiota could produce gamma aminobutyric acid (GABA) that could modulate the gut–brain axis response. Jianpi Jieyu (JPJY) decoction, a traditional Chinese formula, is mainly composed of Astragalus membranaxeus and Radix Pseudostellariae. Although the JPJY decoction has been used to treat the depression in China, the potential action of its antidepressant has not been well understood. Thus this study was aim to investigate the role of JPJY improve gut microbiota homeostasis in the chronic stress induced depressive mice.Methods: The antidepressant effect of JPJY on chronic unpredictable mild stress (CUMS) mice was evaluated by using sucrose preference test, tail suspension test and forced swim test. Fatigue-like behaviors were evaluated using degree of redness, grip strength test, and exhaustive swimming test. The new object recognition test was used to evaluate cognition performance. Fecal samples were collected and taxonomical analysis of intestinal microbial distribution was conducted with 16S rDNA. Serum level of GABA was measured using high performance liquid chromatography (HPLC). The expression of GluR1 and p-Tau protein in the hippocampus was determined using Western blotting.Results: The dose of 9.2 g/kg JPJY produced antidepressant-like effects. JPJY and its major components also modulated gut microbiota diversity in the CUMS mice. Serum level of GABA and the expressions of hippocampal GluR1 and p-Tau were reversed after the administration of JPJY in CUMS mice.Conclusion: JPJY regulates gut microbiota to produce antidepressant-like effect and improve cognition deficit in depressive mice while its molecular mechanism possibly be enhanced NR1 and Tau expression in hippocampus and increased GABA in serum.

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

2021 ◽  
Author(s):  
Teng Zhang ◽  
Can Yang ◽  
Jiang Chu ◽  
Linna Ning ◽  
Peng Zeng ◽  
...  
Keyword(s):  
Psychosocial Stress ◽  
Inflammatory Responses ◽  
Glycogen Synthase ◽  
Preference Test ◽  
Underlying Mechanism ◽  
Related Factor ◽  
Mild Stress ◽  
Nissl Staining ◽  
Force Swimming Test ◽  
Sucrose Preference Test

Abstract 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.

scholarly journals FGF21 restores hippocampual mitochondrial dysfunction via enhancing Nrf2/HO-1 and AMPK/SirT1/PGC-1α signaling pathways to alleviate chronic unpredictable mild stress induced depressive like behaviors in mice

2021 ◽  
Author(s):  
Yun-Tao Zhao ◽  
Ling Shen ◽  
Yong-Ping Zhang ◽  
Lulu Zhang ◽  
Leigang Jin ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Signaling Pathways ◽  
Forced Swim Test ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Expression Level ◽  
Fibroblast Growth Factor 21 ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Immobility Time

Abstract Mitochondrial dysfunction plays a key role in the pathogenesis of depression. Ample research proves mitochondria are a promising target for depression. Fibroblast growth factor 21 (FGF21) exerts roles in neuroprotection and could enhance mitochondria function. Here, the anti-depressive effect of FGF21 was evaluated on a chronic unpredictable mild stress (CUMS)- induced model of depression. The depressive-like behaviors were assessed using sucrose preference test (SPT), forced swim test (FST) and tail suspension test (TST). The results showed that treatment of FGF21 significantly attenuated the decrease in SPT, and dramatically reduced the immobility time in the TST and FST. These effects were associated with enhanced hippocampal mitochondrial function, reflected by FGF21-induced increases in mitochondrial ATP concentration, mitochondrial membrane potential (MMP), and decrease of reactive oxygen species (ROS) levels. At the same time, FGF21 ameliorated oxidative stress in CUMS-exposed mice by enhancing superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase activities, and reducing malondialdehyde (MDA) level in the hippocampus. Mechanistically, we found that CUMS treatment decreased expression level of mitochondrial fusion protein 1 (MFN1), and increased expression level of mitochondrial dynamin-related protein 1 (DRP1). FGF21 administration increased expression of MFN1, and reduced expression of DRP1. Meanwhile, FGF21 treatment promoted the expression levels of Nrf2, HO-1, phosphorylated AMPK, SirT1, PGC-1a in the hippocampus. This study revealed that FGF21 alleviates CUMS induced depressive like behaviors by restoring mitochondria function via enhancing Nrf2/HO-1 and AMPK/SirT1/PGC-1α signaling pathways. It suggested that FGF21 would be a potential therapeutic agent in the management of depression.

Albiflorin Ameliorates Depressive-like Behaviors in Mice Induced by Chronic Unpredictable Mild Stress

2019 ◽  
Vol 18 (1) ◽  
pp. 102-107
Author(s):  
Wang Jun ◽  
Wan Yanfang ◽  
Zheng Nan
Keyword(s):  
Forced Swim Test ◽  
Tail Suspension Test ◽  
Underlying Mechanism ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Tail Suspension ◽  
Sucrose Consumption ◽  
Swim Test ◽  
Forced Swim ◽  
Suspension Test

Depression is a common psychiatric disorder with a high recurrence rate leading to suicidal thoughts in some cases. Albiflorin is a monoterpene glycoside that is commonly used in the treatment of psychiatric disorders. However, the underlying mechanism of albiflorin on depression is unclear and remains to be investigated. To this end, a mouse model of depression was established via chronic unpredictable mild stress treatment. Next, the effects of albiflorin on depression in these mice were evaluated using the sucrose preference test, forced swim test, tail suspension test, and open field test. The results showed that chronic unpredictable mild stress decreased sucrose consumption, while albiflorin (10 mg/kg) treatment significantly increased sucrose consumption just as fluoxetine (10 mg/kg), a drug commonly used to treat depression. Moreover, both albiflorin and fluoxetine demonstrated significant decrease in immobility time in the forced swim test and tail suspension test with no change in spontaneous locomotor activities. Finally, the underlying mechanism of albiflorin was evaluated using western blot. Results showed an up-regulation of phospho-Akt without changing total-Akt, indicating that albiflorin improved the depression symptoms via inactivation of the Akt signaling pathway. Therefore, albiflorin might be a potential therapeutic treatment for depression.

Gemfibrozil has antidepressant effects in mice: Involvement of the hippocampal brain-derived neurotrophic factor system

2018 ◽  
Vol 32 (4) ◽  
pp. 469-481 ◽  
Author(s):  
Yu-Fei Ni ◽  
Hao Wang ◽  
Qiu-Yan Gu ◽  
Fei-Ying Wang ◽  
Ying-Jie Wang ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
Forced Swim Test ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Brain Derived Neurotrophic Factor ◽  
Peroxisome Proliferator ◽  
Mild Stress ◽  
Peroxisome Proliferator Activated Receptor ◽  
Antidepressant Effects ◽  
Bdnf Signaling

Major depressive disorder has become one of the most serious neuropsychiatric disorders worldwide. However, currently available antidepressants used in clinical practice are ineffective for a substantial proportion of patients and always have side effects. Besides being a lipid-regulating agent, gemfibrozil is an agonist of peroxisome proliferator-activated receptor-α (PPAR-α). We investigated the antidepressant effects of gemfibrozil on C57BL/6J mice using the forced swim test (FST) and tail suspension test (TST), as well as the chronic unpredictable mild stress (CUMS) model of depression. The changes in brain-derived neurotrophic factor (BDNF) signaling cascade in the brain after CUMS and gemfibrozil treatment were further assessed. Pharmacological inhibitors and lentivirus-expressed short hairpin RNA (shRNA) were also used to clarify the antidepressant mechanisms of gemfibrozil. Gemfibrozil exhibited significant antidepressant actions in the FST and TST without affecting the locomotor activity of mice. Chronic gemfibrozil administration fully reversed CUMS-induced depressive-like behaviors in the FST, TST and sucrose preference test. Gemfibrozil treatment also restored CUMS-induced inhibition of the hippocampal BDNF signaling pathway. Blocking PPAR-α and BDNF but not the serotonergic system abolished the antidepressant effects of gemfibrozil on mice. Gemfibrozil produced antidepressant effects in mice by promoting the hippocampal BDNF system.

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