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 ◽  
...  

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.

2021 ◽  
Vol 12 ◽  
Author(s):  
Ning Jiang ◽  
Haixia Wang ◽  
Hong Huang ◽  
Jingwei Lv ◽  
Guirong Zeng ◽  
...  

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.


2019 ◽  
Vol 12 (2) ◽  
pp. 981-988
Author(s):  
Venkata Naveen Kumar P. ◽  
Elango P. ◽  
Asmathulla S. ◽  
Kavimani S

The present study aimed at evaluating the effects of lycopene on CMS-induced depressive-like behavioral changes in Wistar rats. In present study, rodents were selected randomly and grouped in to seven groups. Each group consists of six animals. All the groups are subjected to chronic mild stress in an unpredictable manner except the control group, which is free from stress. Behavioral changes induced during chronic mild stress were assessed by conducting the behavioral tests like forced swim test, sucrose preferences test, elevated plus maze test and open field tests in screening depressant and anxiety activity. The data analysis showed chronic mild stress produced depressive and anxiogenic behavior in the experimental rats. A significant increase in the immobility time and decrease in sucrose consumption in sucrose preference test are noted in CMS and vehicle groups. Similarly, in an elevated plus maze a significant decrease in the entries in the open arm and decrease in central square entries, and rearing behavior and increase in the duration of immobility were observed in open field test.Lycopene treatment for 6-weeks significantly decreased immobility time and increased in sucrose consumption observed in the forced swim test and sucrose preference test respectively. Lycopene significantly increased number of entries in the open arm of elevated plus maze and decreased grooming and freezing behavior in open field method. lycopene supplemented dose of 5mg/kg showed an insignificant results in all the behavioral models (p>0.05).The data were expressed as Mean±SD.Data were analyzed and differences between the means were determined by one-way analysis of variance (ANOVA) Using graph pad prism version 5.03 statistical software. In all the tests, differences were considered significant if p<0.05 to be a statistical significant. lycopene possesses antidepressant and mild- anxiolytic activity which may be due to its antioxidant effect that might warrant further studies.


2019 ◽  
Vol 20 (1) ◽  
pp. 195 ◽  
Author(s):  
Jiawei Wu ◽  
Tingting Zhang ◽  
Luping Yu ◽  
Shuai Huang ◽  
Yu Yang ◽  
...  

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.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Yuan Du ◽  
Jian Ruan ◽  
Leiming Zhang ◽  
Fenghua Fu

Jieyu Anshen granule (JY) is a traditional Chinese medicine formula for treating depression and anxiety. The aim of the study was to observe the effects of JY on poststroke depression (PSD) and investigate the underlying mechanism. PSD rat model was developed by middle cerebral artery occlusion following chronic unpredictable mild stress in conjunction with isolation rearing. We performed behavioral tests, Western blot, ELISA, and BrdU/NeuN staining. Treatment with JY showed significant antidepressant effect in open-field and sucrose preference tests, as well as significant improvement in beam-walking, cylinder, grip strength, and water maze tests. In addition, treatment with JY could restore the levels of neurotransmitters and decrease the levels of hormone and inflammation cytokines in serum and brain. Treatment with JY also showed significant regulation in the expression of neurotransmitter receptors and NF-κB/IκB-α signaling in the prefrontal cortex and hippocampus. Moreover, the numbers of newborn neurons in the hippocampus were increased by treatment with JY. Our results suggest that JY could ameliorate PSD and improve the neurological and cognitive functions. The antidepressive effect may be associated with the modulation of JY on monoamine system, neuroendocrine, neuroinflammation, and neurogenesis.


2022 ◽  
pp. 1-9
Author(s):  
Qi Wang ◽  
Hongsheng Bi ◽  
Hongfei Huang ◽  
Yitong Wang ◽  
Lili Gong ◽  
...  

<b><i>Background:</i></b> The precise physiological mechanisms of acupuncture in the treatment of depression are still unknown. This study aimed to observe the effects of electroacupuncture (EA) on depression-like behavior of mouse in chronic mild stress (CMS) model and explore the underlying mechanism. <b><i>Methods:</i></b> The depression model was established by using CMS method for 6 weeks. After the third week of the CMS paradigm, EA treatment was performed daily for 15 min over a period of 3 weeks. The antidepressant-like effects of EA were evaluated using the sucrose preference test and the forced swimming test (FST). The protein levels of the nuclear factor-kappa B (NF-κB), p-NF-κB, inhibitor of NF-κB, p-IκBα, NOD-like receptor protein 3, interleukin (IL)-6, IL-1β, IL-18, and tumor necrosis factor-α (TNF-α) in hippocampus of mice were detected. <b><i>Results:</i></b> Sucrose preference was decreased after 6 weeks of CMS and the effects of CMS was reversed by EA. CMS increased immobility time and decreased latency to the first immobility in the FST test, but these effects were reversed by EA. CMS-induced nuclear entry of NF-κB (nuclear/cytoplasmic ratio of NF-κB) with an increase in protein levels of p-NF-κB and p-IκBα in the hippocampus. The CMS also increased NLRP3 levels in the hippocampus. However, these effects were reversed by EA. In addition, the levels of IL-6, IL-1β, IL-18, and TNF-α in the hippocampus were increased by CMS, and these effects of stress were reversed by EA. <b><i>Conclusion:</i></b> EA prevented CMS-induced depressive-like behaviors by inhibiting NF-κB/NLRP3 inflammatory pathway.


2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Tao Li ◽  
Dou Wang ◽  
Bingbing Zhao ◽  
Yongmei Yan

Background.The neurotrophic pathway regulated by the brain-derived neurotrophic factor (BDNF) plays a crucial role in the pathogenesis of poststroke depression (PSD). How the traditional Chinese medicine compound preparation Xingnao Jieyu (XNJY) decoction regulates the neurotrophic pathway to treat PSD is unclear.Objective.This study aimed to investigate the antidepressant effect of XNJY decoction on a rat model of PSD and the molecular mechanism intervening in the neurotrophic pathway.Methods.After a middle cerebral artery occlusion model was established, chronic unpredictable mild stress was applied for 21 days to prepare a PSD model. XNJY groups and a fluoxetine (Flu) group of rats were intragastrically administered with XNJY and Flu, respectively, for 21 consecutive days. Depressive-like behaviors, including sucrose preference, open field test, and forced swimming test, were assessed. The survival and apoptosis of cortical and hippocampal neurons were evaluated by immunofluorescence assay and TUNEL staining. The contents of serotonin (5-HT), norepinephrine (NE), and BDNF in the cortex and hippocampus were determined by ELISA. The protein levels of BDNF, p-ERK/ERK, and p-CREB/CREB in the cortical and hippocampal regions were tested by Western blot.Results.The depressive-like behaviors markedly improved after XNJY and Flu treatment. XNJY and Flu promoted neuronal survival and protected cortical and hippocampal neurons from apoptosis. XNJY also increased the contents of 5-HT, NE, and BDNF and recovered the protein levels of p-ERK/ERK, p-CREB/CREB, and BDNF in the cortical and hippocampal regions.Conclusion.These results indicated that the XNJY decoction exerts an obvious antidepressant effect, which may be due to the regulation of the BDNF/ERK/CREB signaling pathway.


2021 ◽  
Author(s):  
Teng Zhang ◽  
Can Yang ◽  
Jiang Chu ◽  
Linna Ning ◽  
Peng Zeng ◽  
...  

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.


Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 516 ◽  
Author(s):  
Te-Hsuan Tung ◽  
Yu-Tang Tung ◽  
I-Hsuan Lin ◽  
Chun-Kuang Shih ◽  
Ngan Thi Kim Nguyen ◽  
...  

Background: This study investigated the effects of fish oil and olive oil in improving dysbiosis and depressive-like symptoms. Methods and results: Male rats were fed normal, fish oil-rich or olive oil-rich diets for 14 weeks. Chronic mild stress (CMS) was administered from week 2. The sucrose preference test (SPT) and forced swimming test (FST) were used to determine depressive-like behavior. The SPT results revealed that the CMS, CMS with imipramine (CMS+P) treatment, and CMS with olive oil diet (CMS+O) groups exhibited significantly reduced sucrose intake from week 8, whereas the fish oil diet (CMS+F) group exhibited significantly reduced sucrose intake from week 10. The FST results showed that the immobile time of the CMS+F group was significantly less than that of the CMS-only group. Next generation sequencing (NGS) results showed CMS significantly reduced the abundance of Lactobacillus and increased that of Marvinbryantia and Ruminiclostridium_6. However, the CMS+F group showed an increase in the abundance of Eisenbergiella, Ruminococcaceae_UCG_009, and Holdemania, whereas the CMS+O group showed an increase in the abundance of Akkermansia. Conclusions: CMS stimuli altered the gut microbiome in depressed rats. Fish oil and olive oil exerted part of a prebiotic-like effect to ameliorate dysbiosis induced by CMS. However, only fish oil ameliorated depressive-like symptoms.


Author(s):  
Alisha Abbas ◽  
Narendra Kumar ◽  
Sarvesh Singh ◽  
Rahul Kumar ◽  
Akhlaque Ahmad ◽  
...  

Background: Depression was seen to be associated with an increased level of inflammatory biomarkers along with the disturbance in the monoamine neurotransmitter system. Current therapies are mostly focussed on the neurotransmitters imbalance but due to increasing cases of treatment failure there is a need to shift our treatment focus to other potential therapies. This study aimed to evaluate the preventive role of aspirin and metformin in stress induced model of depression in wistar rats.Methods: Fifty four wistar rats were randomly divided into nine groups as normal control, experimental control, aspirin (30 mg/kg, 60 mg/kg), metformin (50 mg/kg, 100 mg/kg), two combination groups and imipramine (15 mg/kg). Depression model was created by the induction of chronic unpredictable mild stress (CUMS) for consecutive 28 days. Behavioural assessment was done by evaluating immobility time in forced swim test (FST) and sucrose preference ratio (SPR) in sucrose preference test. The data were analysed by analysis of variance (ANOVA) test using SPSS software. P<0.05 was considered to be statistically significant.Results: The CUMS led to an increase in immobility time and decrease in SPR. Aspirin and Metformin alone and their combinations showed statistically significant response in preventing the immobility time to increase (p<0.001) and SPR to decrease (p<0.001). However the response of Aspirin was comparable with Imipramine but the response of Metformin was not as significant as of Imipramine (p>0.05).Conclusions: Aspirin and metformin might have a potential role in the prevention of depression.


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