Gastrodiae Rhizoma Water Extract Ameliorates Hypothalamic–Pituitary–Adrenal Axis Hyperactivity and Inflammation Induced by Chronic Unpredictable Mild Stress in Rats

Gastrodiae Rhizoma is a highly valuable traditional herbal medicine commonly used to treat neurological disorders. The present study is designed to determine the antidepressant-like effect of the Gastrodiae Rhizoma water extract (GRWE) on a depression model and the potential mechanisms. The chronic unpredictable mild stress (CUMS) rat model was used to induce depression. The sucrose preference test, open field test, forced swimming test, and tail suspension test were performed to assess the depressive-like behaviors, respectively. Hypothalamic–pituitary–adrenal (HPA) function was measured via plasma corticosterone (CORT), adrenocorticotrophic hormone (ACTH), hypothalamic corticotropin-releasing factor (CRF), and glucocorticoid receptor (GR) concentrations. Plasma concentrations of proinflammatory cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were also evaluated. The results showed that GRWE significantly attenuates the behavioral abnormalities in CUMS rats, as shown by elevated sucrose consumption, raised locomotor activity, and reduced immobility duration. Moreover, GRWE treatment reduced CORT, ACTH, CRF, and GR levels and decreased the plasma IL-1β, IL-6, and TNF-α concentrations. These findings indicate that GRWE improves depressive behaviors in a chronic stress model of rats; its effect may be ascribed to the modulation of the HPA axis activity and inflammatory response.

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ANTIDEPRESSANT-LIKE ACTIVITY OF FLOWERS OF TECOMELLA UNDULATA IN MICE SUBJECTED TO CHRONIC UNPREDICTABLE MILD STRESS

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v12i1.28981 ◽

2019 ◽

Vol 12 (1) ◽

pp. 130

Author(s):

Dinesh Dhingra ◽

Deepak Deepak

Keyword(s):

Young Male ◽

Ethanol Extract ◽

Preference Test ◽

Tail Suspension Test ◽

Plasma Corticosterone ◽

Sucrose Preference ◽

Mild Stress ◽

Chronic Unpredictable Mild Stress ◽

Tecomella Undulata ◽

Plasma Nitrite

Objective: Flowers of Tecomella undulata have been reported to be a rich source of flavonoids such as rutin and quercetin. The present study was designed to evaluate the effect of ethanol extract of flowers of T. undulata on chronic unpredictable mild stress (CUMS)-induced depression in Swiss young male albino mice.Methods: The mice were subjected to CUMS for 21 successive days. Ethanol extract of the flowers (50, 100, and 200 mg/kg, p.o.) and fluoxetine (20 mg/kg, p.o.) per se was administered for 21 successive days to separate groups of unstressed and stressed mice. Tail suspension test (TST) and sucrose preference test were used to evaluate the effect of the extract on depression-like behavior in mice.Results: Extract of flowers of T. undulata (100 and 200 mg/kg) significantly decreased immobility period of stressed mice in TST, indicating significant antidepressant-like activity of the extract. Stress-induced reduced sucrose preference was significantly restored by the extract. There was no significant effect on locomotor activity of mice by the extract and fluoxetine. The extract significantly reversed stress-induced increase in brain malondialdehyde levels; plasma nitrite and corticosterone levels; and also significantly reversed the stress-induced decrease in reduced glutathione and catalase levels. There was no significant effect of the extract on brain MAO-A activity in both unstressed and stressed mice.Conclusion: These results indicated that ethanol extract of flowers of T. undulata showed significant antidepressant-like activity in mice subjected to CUMS, probably through alleviation of oxidative stress and decrease in plasma corticosterone levels.

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ANTIDEPRESSANT-LIKE ACTIVITY OF FLOWERS OF TECOMELLA UNDULATA IN MICE SUBJECTED TO CHRONIC UNPREDICTABLE MILD STRESS

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2019.v12i1.28981 ◽

2019 ◽

Vol 12 (1) ◽

pp. 130

Author(s):

Dinesh Dhingra ◽

Deepak Deepak

Keyword(s):

Young Male ◽

Ethanol Extract ◽

Preference Test ◽

Tail Suspension Test ◽

Plasma Corticosterone ◽

Sucrose Preference ◽

Mild Stress ◽

Chronic Unpredictable Mild Stress ◽

Tecomella Undulata ◽

Plasma Nitrite

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

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2019.v12i12.35542 ◽

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.

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Antidepressant Like Effect of Sodium Orthovanadate in A Mouse Model of Chronic Unpredictable Mild Stress.

10.21203/rs.3.rs-643262/v1 ◽

2021 ◽

Author(s):

Angel Joshi ◽

Ansab Akhtar ◽

Priyanka Saroj ◽

Anurag Kuhad ◽

Sangeeta Pilkhwal Sah

Keyword(s):

Molecular Mechanisms ◽

Nitrosative Stress ◽

Tyrosine Phosphatase ◽

Preference Test ◽

Tail Suspension Test ◽

Mild Stress ◽

Chronic Unpredictable Mild Stress ◽

Sodium Orthovanadate ◽

Behavioral Tests ◽

Oxidative And Nitrosative Stress

Abstract Depression is a psychiatric disorder characterized by low esteem, anhedonia, social deficit, and lack of interest. Decreased BDNF and impaired TrKB signaling be associated with depression. In our study, depressive-like behavior was induced in mice by chronic unpredictable mild stress (CUMS) model. Various behavioral tests like tail suspension test (TST), open field test (OFT), and sucrose preference test (SPT); biochemical analyses for corticosterone, reduced glutathione (GSH), lipid peroxidation (LPO), superoxide dismutase (SOD), nitric oxide (NO) and ELISA for BDNF were performed. Body weight was measured every week. Depressive-like behavior was associated with increased oxidative stress in the brain and subsequent reduction of BDNF. Further, sodium orthovanadate (SOV), a protein tyrosine phosphatase inhibitor was used as a test drug as it is reported to stimulate BDNF levels. Sodium orthovanadate (SOV-5 mg/kg, 10 mg/kg) and fluoxetine (10 mg/kg) was given to mice orally for 21 days before 30 minutes of stress induction. The behavioral tests reflected depressive-like behavior in CUMS, which was attenuated by both SOV and fluoxetine. SOV at 10 mg/kg has demonstrated significant results in our study by decreasing malondialdehyde levels (MDA/LPO), NO levels, and increasing GSH and SOD in both the cortex and hippocampus. Besides, ELISA revealed the elevation of BDNF levels in the treatment groups (SOV-5 mg/kg, 10 mg/kg, and FLX-10 mg/kg) as compared with the disease group (CUMS). Therefore, the treatment with SOV appeared to reverse both oxidative and nitrosative stress. Decreased serum corticosterone levels (SOV-5 mg/kg, 10 mg/kg); FLX (10 mg/kg) + SOV (5 mg/kg); FLX-10 mg/kg and per-se) and elevated BDNF level (SOV-5 mg/kg, 10 mg/kg and FLX-10 mg/kg) were associated with attenuation of depressive-like behavior. The findings of this preliminary study indicate that SOV has the potential to restore antidepressant-like effect or prevention of stress-induced anhedonia and so further molecular mechanisms will be warranted for clinical translation.

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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

10.21203/rs.3.rs-1003374/v1 ◽

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.

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Antidepressant-Like Effects of Cordycepin in a Mice Model of Chronic Unpredictable Mild Stress

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2014/438506 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 34

Author(s):

Zhang Tianzhu ◽

Yang Shihai ◽

Du Juan

Keyword(s):

Preference Test ◽

Antidepressant Activity ◽

Tail Suspension Test ◽

Positive Control ◽

Mild Stress ◽

Chronic Unpredictable Mild Stress ◽

Mice Model ◽

Bdnf Expression ◽

Beneficial Effects ◽

Control Drug

Cordycepin (3′-deoxyadenosine), a major bioactive component isolated fromCordyceps militaris, has multiple pharmacological activities. This study is attempted to investigate whether cordycepin (COR) possesses beneficial effects on chronic unpredictable mild stress- (CUMS-) induced behavioral deficits (depression-like behaviors) and explore the possible mechanisms. ICR mice were subjected to chronic unpredictable mild stress for 42 consecutive days. Then, COR and fluoxetine (FLU, positive control drug) were administered for 21 consecutive days at the last three weeks of CUMS procedure. The classical behavioral tests, open field test (OFT), sucrose preference test (SPT), tail suspension test (TST), and forced swimming test (FST), were applied to evaluate the antidepressant effects of COR. Then the serotonin (5-HT) and noradrenaline (NE) concentrations in hippocampal were evaluated by HPLC; tumor necrosis factor-α(TNF-α) and interleukin-6 (IL-6) in hippocampal were evaluated, and the proteins of TNF-α, IL-6, NF-κBP65 5-HTreceptor (5-HTR), and brain-derived neurotrophic factor (BDNF) in hippocampal were evaluated by Western blot. Our results indicated that 6 weeks of CUMS exposure induced significant depression-like behavior, with low 5-HT and NE levels, high TNF-αand IL-6 in brain and high hippocampal TNF-α, IL-6, P-NF-κBP65, and 5-HTR levels, and low BDNF expression levels. Whereas, chronic COR (20, 40 mg/kg) treatments reversed the behavioral deficiency induced by CUMS exposure, treatment with COR normalized the change of TNF-α, IL-6, 5-HT, and NE levels, which demonstrated that COR could partially restore CUMS-induced 5-HT receptor impairments and inflammation. Besides, hippocampal BDNF expressions were also upregulated after COR treatments. In conclusion, COR remarkably improved depression-like behavior in CUMS mice and its antidepressant activity is mediated, at least in part, by the upregulating BDNF and downregulating 5-HTR levels and inflammation in hippocampus.

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Huanglian-Wendan Decoction Inhibits NF-κB/NLRP3 Inflammasome Activation in Liver and Brain of Rats Exposed to Chronic Unpredictable Mild Stress

Mediators of Inflammation ◽

10.1155/2018/3093516 ◽

2018 ◽

Vol 2018 ◽

pp. 1-15 ◽

Cited By ~ 10

Author(s):

Ke-Ke Jia ◽

Hong Ding ◽

Han-Wen Yu ◽

Tie-Jun Dong ◽

Ying Pan ◽

...

Keyword(s):

Nlrp3 Inflammasome ◽

Inflammatory Responses ◽

Common Mental Disorder ◽

Interleukin 1 ◽

Water Extract ◽

Inflammasome Activation ◽

Mild Stress ◽

Chronic Unpredictable Mild Stress ◽

Nlrp3 Inflammasome Activation ◽

Anti Inflammation

Depression is a common mental disorder in modern society. A traditional Chinese medicine Huanglian-Wendan decoction with potential anti-inflammation is used as a clinical antidepressant. Our previous study showed central and peripheral inflammatory responses in a rat model of depression developed by chronic unpredictable mild stress (CUMS). Here, we investigated the anti-inflammatory activity and mechanism of Huanglian-Wendan decoction in CUMS rats. LC-MS/MS and HPLC were performed to determine the major compounds in water extract of this decoction. This study showed that Huanglian-Wendan decoction significantly increased sucrose consumption and reduced serum levels of interleukin-1 beta (IL-1β), IL-6, and alanine aminotransferase (ALT) in CUMS rats. Moreover, this decoction inhibited nuclear entry of nuclear factor-kappa B (NF-κB) with the reduction of phosphorylated protein of NF-κB (p-NF-κB) and inhibitor of NF-κB alpha (p-IκBα) and downregulated protein of nod-like receptor family pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), cysteinyl aspartate-specific proteinase-1 (Caspase-1), and IL-1β in liver and brain regions of CUMS rats. These findings demonstrated that Huanglian-Wendan decoction had antidepressant activity with hepatoprotection in CUMS rats coinciding with its anti-inflammation in both periphery and central. The inhibitory modulation of NF-κB and NLRP3 inflammasome activation by Huanglian-Wendan decoction may mediate its antidepressant action.

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Neuroprotective Potential of Sodium Orthovanadate in a Mouse Model of Chronic Unpredictable Mild Stress.

10.21203/rs.3.rs-498351/v1 ◽

2021 ◽

Author(s):

Angel Joshi ◽

Ansab Akhtar ◽

Anurag Kuhad ◽

Sangeeta Pilkhwal Sah

Keyword(s):

Molecular Mechanisms ◽

Nitrosative Stress ◽

Preference Test ◽

Tail Suspension Test ◽

Mild Stress ◽

Chronic Unpredictable Mild Stress ◽

Sodium Orthovanadate ◽

Oxidative And Nitrosative Stress ◽

Behavioral Studies ◽

Biochemical Analyses

Abstract Depression is a psychiatric disorder characterized by low-esteem, anhedonia, social deficit, and lack of interest. Decreased BDNF and impaired TrKB signaling have been found to be associated in depression. Moreover, oxidative stress in the brain and subsequent reduction of BDNF have a prominent role in psychiatric disorders. In our study, depressive-like behavior was induced in mice by chronic unpredictable mild stress (CUMS) model. Further, sodium orthovanadate (SOV), a protein tyrosine phospahatase was used as a test drug as it is reported to stimulate BDNF levels. Sodium orthovanadate (SOV-5 mg/kg, 10 mg/kg) and fluoxetine (10 mg/kg) were given to mice orally for 21 days prior 30 minutes of stress induction. Various behavioral studies like tail suspension test (TST), open field test (OFT), and sucrose preference test (SPT); biochemical analyses for corticosterone, reduced glutathione (GSH), lipid peroxidation (LPO), superoxide dismutase (SOD), nitric oxide (NO) and ELISA for BDNF were performed. Body weight was measured on a weekly basis. The behavioral tests reflected depressive-like behavior in CUMS, which was attenuated by SOV and fluoxetine. SOV (10 mg/kg) significantly decreased malondialdehyde levels, NO, whereas increased GSH and SOD in both the cortex and hippocampus. Besides, ELISA revealed the elevation of BDNF levels in the treatment groups compared with the disease group (CUMS). Therefore, the treatment with SOV appeared to reverse both oxidative and nitrosative stress. Elevated BDNF level was associated with attenuation of depressive-like behaviors and serum corticosterone levels. The findings of this preliminary study indicates that SOV has potential to restore mood and social interaction in depression and so further molecular mechanisms will be warranted for clinical translation.

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Oral supplementation with geranium oil or anise oil ameliorates depressed rat-related symptoms through oils antioxidant effects

Journal of Complementary and Integrative Medicine ◽

10.1515/jcim-2019-0028 ◽

2019 ◽

Vol 17 (2) ◽

Cited By ~ 1

Author(s):

Karima A. El-Shamy ◽

Khaled M. M. Koriem ◽

Nevein N. Fadl ◽

Marwa H. A. El-Azma ◽

Mahmoud S. S. Arbid ◽

...

Keyword(s):

Cerebral Cortex ◽

Oral Intake ◽

Chronic Mild Stress ◽

Preference Test ◽

Tail Suspension Test ◽

Psychiatric Disease ◽

Albino Rats ◽

Mild Stress ◽

Immobility Time ◽

Antioxidant Effects

AbstractBackgroundDepression is a psychiatric disease condition and the chronic mild stress (CMS) model is a well-known and valuable animal model of depression. Geranium oil and anise oil were chosen for such a study. The aim of this research was to establish the geranium oil and anise oil effect to ameliorate CMS-related symptoms.MethodsThis research included 80 male albino rats each group of 10 rats and the animals were divided into two major groups: normal and CMS. The normal group was subdivided into four (control, geranium oil, anise oil and venlafaxine drug) subgroups treated orally with saline, geranium oil, anise oil and venlafaxine drug, respectively, for 4 weeks. The CMS group was subdivided into four (CMS without any treatment, CMS + geranium oil, CMS + anise oil and CMS + venlafaxine drug) subgroups treated orally with geranium oil, anise oil and venlafaxine drug, respectively, for 4 weeks.ResultsThe sucrose consumption in sucrose preference test, the distance traveled test and center square entries test were decreased, while center square duration test, immobility time in tail suspension test and floating time in forced swimming test were increased in CMS. The superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase and catalase levels decreased but malondialdehyde and nitric oxide levels increased in brain cerebral cortex and hippocampus areas in CMS. The oral intake of geranium oil and anise oil pushes all these parameters to approach the control levels. These results were supported by histopathological investigations of both brain cerebral cortex and hippocampus tissues.ConclusionsGeranium oil and anise oil ameliorate CMS-related symptoms and this effect were related to the antioxidant effects of oils.

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The Antidepressant Effect ofAngelica sinensisExtracts on Chronic Unpredictable Mild Stress-Induced Depression Is Mediated via the Upregulation of the BDNF Signaling Pathway in Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/7434692 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 14

Author(s):

Jun Shen ◽

Junjian Zhang ◽

Min Deng ◽

Yue Liu ◽

Yuan Hu ◽

...

Keyword(s):

Signaling Pathway ◽

Preference Test ◽

Camp Response Element Binding ◽

Sucrose Preference ◽

Antidepressant Effect ◽

Force Swim Test ◽

Mild Stress ◽

Chronic Unpredictable Mild Stress ◽

Traditional Chinese Herbal Medicine ◽

Bdnf Signaling

Angelica sinensis(AS), a traditional Chinese herbal medicine, has pharmaceutical effects on menstrual illness, cerebrovascular diseases, cardiovascular diseases, and cognitive impairments. However, until recently, few studies had explored its antidepressant effect. The current study attempts to investigate the effect of AS extracts on chronic unpredictable mild stress- (CUMS-) induced depression in rats. Male SD rats were exposed to a CUMS-inducing procedure for 5 weeks, resulting in rodent depressive behaviors that included reduced sucrose consumption and lessened sucrose preference ratios in sucrose preference test, prolonged immobility times and decreased struggling time in force swim test, and decreased locomotor activity in open field test. Moreover, the expression of brain derived neurotrophic factor (BDNF) and the phosphorylation of cAMP-response element binding protein (CREB) and extracellular signal-regulated protein kinase (ERK 1/2) were markedly decreased in the hippocampus in depressed rats. However, chronically treating the depressed rats with AS (1 g/kg) normalized their depression-related behaviors and molecular profiles. In conclusion, in the present study, we show that AS extracts exerted antidepressant effects that were mediated by the BDNF signaling pathway: in AS-treated depressed rats, the expression of the BDNF protein and the phosphorylation of its downstream targets (ERK 1/2, CREB) were upregulated in the hippocampus.

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