scholarly journals Echinacoside exhibits antidepressant-like effects through AMPAR–Akt/ERK–mTOR pathway stimulation and BDNF expression in mice

2022 ◽  
Vol 17 (1) ◽  
Author(s):  
Han-Wen Chuang ◽  
Tse-Yen Wang ◽  
Chih-Chia Huang ◽  
I-Hua Wei
Keyword(s):  
Depressive Disorders ◽  
Neuroprotective Effect ◽  
Underlying Mechanism ◽  
Mtor Pathway ◽  
Antidepressant Effect ◽  
Bdnf Expression ◽  
Echinacea Angustifolia ◽  
Extracellular Signal ◽  
Wide Range ◽  
Swimming Test

Abstract Background Several natural products have been demonstrated to be effective in the treatment of depressive disorders. Echinacoside, a naturally occurring phenol extracted from Cistanche tubulosa, Echinacea angustifolia, and Cistanche spp, has a wide range of physiological effects, such as antioxidation, neuroprotection, anti-inflammatory, and immunoregulation, which are closely related to depression. In addition, echinacoside can activate protein kinase B (Akt), extracellular signal–regulated kinase (ERK), and brain-derived neurotrophic factor (BDNF) in the brain. A key downstream event of the Akt, ERK, and BDNF signaling pathways, namely mechanistic target of rapamycin (mTOR) signaling, plays a crucial role in generating an rapid antidepressant effect. Thus, echinacoside is a promising therapeutic agent for depression. However, research regarding the role of echinacoside in antidepressant effect and brain mTOR activation remains lacking. Materials and methods The forced swimming test and Western blot analysis in C57BL/6 mice was used to investigate the antidepressant-like activities of echinacoside and the underlying mechanism involved inα-amino3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)–Akt/ERK–mTOR pathway. Results We confirmed the suggestions by previous reports that echinacoside activates Akt/ERK signaling and further demonstrated that echinacoside could provide antidepressant-like effects in mice via the activation of AMPAR–Akt/ERK–mTOR pathway in the hippocampus. Conclusions To the best of our knowledge, our study is the first to reveal that echinacoside is a potential treatment for depressive disorders. Moreover, the present study suggests a mechanism for the neuroprotective effect of echinacoside.

scholarly journals Echinacoside Exhibits Antidepressant-like Effects Through AMPAR–Akt/ERK–mTOR Pathway Stimulation and BDNF Expression in Mice

2021 ◽  
Author(s):  
Han-Wen Chuang ◽  
Tse-Yen Wang ◽  
Chih-Chia Huang ◽  
I-Hua Wei
Keyword(s):  
Depressive Disorders ◽  
Neuroprotective Effect ◽  
Underlying Mechanism ◽  
Receptor Activation ◽  
Mtor Signaling ◽  
Erk Signaling ◽  
Antidepressant Effect ◽  
Bdnf Expression ◽  
Wide Range ◽  
Glutamatergic Signaling

Abstract Background: Several natural products have been demonstrated to be effective in the treatment of depressive disorders. Echinacoside, a naturally occurring phenol extracted from Cistanche tubulosa, Echinacea angustifolia, and Cistanche spp, has a wide range of physiological effects, such as antioxidation, neuroprotection, anti-inflammatory, and immunoregulation, which are closely related to depression. In addition, echinacoside can activate protein kinase B (Akt), extracellular signal–regulated kinase (ERK), and brain-derived neurotrophic factor (BDNF) in the brain. A key downstream event of the Akt, ERK, and BDNF signaling pathways, namely mechanistic target of rapamycin (mTOR) signaling, plays a crucial role in generating an antidepressant effect. Thus, echinacoside is a promising therapeutic agent for depression. However, research regarding the role of echinacoside in brain mTOR activation and antidepressant effect remains lacking. Materials and methods: The forced swimming test in C57BL/6 mice was used to investigate the antidepressant-like activities of echinacoside and the underlying mechanism involved in glutamatergic signaling. Results: We confirmed the suggestions by previous reports that echinacoside activates Akt/ERK signaling and further demonstrated that echinacoside triggers mTOR signaling and α-amino3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor activation in the Akt/ERK signaling pathway downstream and upstream, respectively, and upregulates BDNF in the hippocampus of mice to exhibit antidepressant-like activities. Conclusion: To the best of our knowledge, our study is the first to reveal that echinacoside is a potential treatment for depressive disorders. Moreover, the present study suggests a mechanism for the neuroprotective effect of echinacoside.

Cellular and molecular mechanisms of the brain-derived neurotrophic factor in physiological and pathological conditions

2016 ◽  
Vol 131 (2) ◽  
pp. 123-138 ◽  
Author(s):  
Veronica Begni ◽  
Marco Andrea Riva ◽  
Annamaria Cattaneo
Keyword(s):  
Synaptic Plasticity ◽  
Stress Response ◽  
Neurotrophic Factor ◽  
Molecular Mechanisms ◽  
Depressive Disorders ◽  
Brain Derived Neurotrophic Factor ◽  
Mitogen Activated Protein Kinase ◽  
Bdnf Expression ◽  
Pathological Conditions ◽  
Wide Range

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a key role in the central nervous system, promoting synaptic plasticity, neurogenesis and neuroprotection. The BDNF gene structure is very complex and consists of multiple 5′-non-coding exons, which give rise to differently spliced transcripts, and one coding exon at the 3′-end. These multiple transcripts, together with the complex transcriptional regulatory machinery, lead to a complex and fine regulation of BDNF expression that can be tissue and stimulus specific. BDNF effects are mainly mediated by the high-affinity, tropomyosin-related, kinase B receptor and involve the activation of several downstream cascades, including the mitogen-activated protein kinase, phospholipase C-γ and phosphoinositide-3-kinase pathways. BDNF exerts a wide range of effects on neuronal function, including the modulation of activity-dependent synaptic plasticity and neurogenesis. Importantly, alterations in BDNF expression and function are involved in different brain disorders and represent a major downstream mechanism for stress response, which has important implications in psychiatric diseases, such as major depressive disorders and schizophrenia. In the present review, we have summarized the main features of BDNF in relation to neuronal plasticity, stress response and pathological conditions, and discussed the role of BDNF as a possible target for pharmacological and non-pharmacological treatments in the context of psychiatric illnesses.

scholarly journals Differentiated approach and indications for optimization of agomelatine therapy for endogenous depression

2019 ◽  
Vol 11 (2) ◽  
pp. 71-77
Author(s):  
L. I. Abramova ◽  
G. P. Panteleeva ◽  
I. Yu. Nikiforova ◽  
T. E. Novozhenova
Keyword(s):  
Depressive Disorders ◽  
Rating Scales ◽  
Rating Scale ◽  
Treatment Cycle ◽  
Endogenous Depression ◽  
Good Effect ◽  
Antidepressant Effect ◽  
Antidepressive Effect ◽  
Wide Range ◽  
Days Of Therapy

Objective: to develop and justify differentiated indications for the use of agomelatine (valdoxan) to treat the typological variants of endogenous depressions with varying severity on the basis of an analysis of its therapeutic efficacy.Patients and methods. An open prospective study was conducted using the clinical, psychopathological, and psychometric rating scales: the Hamilton Depression Rating Scale (HAMD-21); Udvalg for Kliniske Undersњgelser Scale (UKU); the Snaith-Hamilton Pleasure Scale (SHAPS) for assessing anhedonic disorders, and statistical methods. Examinations were made in 56 patients (mean age, 34.9 years) with moderate and severe endogenous depression within affective psychosis (n=42) and shift-like schizophrenia (n=14) (ICD-10 items F31.3–4; F32.1–2, and F33.1–2). The patients received a cycle treatment with agomelatine (valdoxan) 25–50 mg once a day in the evening for 4–8 weeks. The patients' status was evaluated over time on fixed days from a reduction in the mean total score (MTS) of the respective scales as insignificant (less than 19% reduction in disorders), moderate (20–49%), good (50–69%), and excellent (70% or more) effects. The effect of agomelatine was analyzed in two patient groups. The specific features of the antidepressive effect and its dynamics in the presence of endogenous depressions of different typologies (melancholic, anxious, and adynamic depressions) were studied in Group 1 (n=26); the effect of agomelatine on anhedonic endogenous depressions and manifestations of anhedonia in different mental activity areas (interests, social activity, emotional engagement and eating/drinking) was investigated in Group 2 (n=30).Results and discussion. There was a good tolerance and a high antidepressant activity of agomelatine during its treatment cycle for moderate and severe endogenous depressions. A significant improvement (an 84.4% reduction in HAMD-21 MTS) was noted in patients at 3 and 4 weeks of the treatment cycle and consistently persisted at a subsequent follow-up. Agomelatine showed a good effect (a 50% or more reduction in HAMD-21 MTS) just at 14 days of therapy. The drug was observed to have a balanced antidepressant effect, significant thymoleptic, stimulant, anxiolytic, and antianhedonic activities (reductions in the MTS of depressive disorders by 90.83, 84.9, 82.39, and 78.9%, respectively).Conclusion. The universal spectrum of the antidepressive effect of agomelatine, its good tolerability, high efficacy, and rapid improvement makes it the drug of choice in treating a wide range of psychopathological endogenous depressions: melancholic, apatho-adynamic, anxious, and anhedonic ones.

scholarly journals Secondary metabolismin in Annonaceae: potencial source of drugs

2014 ◽  
Vol 36 (spe1) ◽  
pp. 141-146
Author(s):  
Mariano Martínez-Vázquez ◽  
Rosa Estrada-Reyes
Keyword(s):  
Depressive Disorders ◽  
Forced Swimming Test ◽  
Antidepressant Drugs ◽  
Hplc Method ◽  
Antidepressant Effect ◽  
Repeated Treatment ◽  
Dopaminergic Transmission ◽  
Aerial Parts ◽  
Annona Cherimola ◽  
Swimming Test

Several species of Annona (Annonaceae) are used in traditional Mexican medicine by their anti-anxiety, anticonvulsant and tranquilizing properties. It has been reported that the alkaloids isolated from some species of the Annona have affinity to serotonergic 5-HT1A receptors and modulate dopaminergic transmission, which is involved in depressive disorders. In this review it is showed the results of the antidepressant-like effect of an alkaloid extract from the aerial parts of Annona cherimola (TA) in mice. The antidepressant-like effect was evaluated in the forced swimming test. To elucidate a possible mechanism of action, experiments of synergism with antidepressant drugs, such as imipramine (IMI), clomipramine (CLIMI), and fluoxetine (FLX), were carried out. The neurotransmitter content (DA: dopamine, 5HT: serotonin and its metabolites, HVA: homovanillic acid and 5HIAA:5-hydroxyindoleacetic) in the whole brain of mice were also determined by HPLC method. The results showed that repeated treatment with TA produced antidepressant-like effects in mice. This effect was not related to an increase in locomotor activity. Administration of TA facilitated the antidepressant effect of IMI and CLIMI as well as increased the turnover of DA and 5-HT. The alkaloids: 1,2-dimethoxy-5, 6.6 to 7-tetrahydro-4H-dibenzoquinoline-3,8,9,10-tetraol, anonaine, liriodenine, and nornuciferine were the main constituents of TA.

scholarly journals Investigation of the antidepressant effects of Shu-Gan-Jie- Yu granule and its mechanism of action

2020 ◽  
Vol 19 (9) ◽  
pp. 1927-1931
Author(s):  
Li-shu Gao ◽  
Min Wu ◽  
Yue Gao ◽  
En-ping Xu ◽  
Jian Xie
Keyword(s):  
Forced Swimming Test ◽  
Open Field Test ◽  
Tail Suspension Test ◽  
Antidepressant Effect ◽  
Bdnf Expression ◽  
Mobility Performance ◽  
Antidepressant Effects ◽  
Swimming Test ◽  
Mice Brain ◽  
The Brain

Purpose: To study the antidepressant effects of Shu-Gan-Jie-Yu granule (SJG) and its possible mechanisms in mice.Methods: The anti-depressive effects of SJG were evaluated by three techniques, viz, forced swimming test (FST), tail suspension test (TST) and open field test (OFT). The levels of the neurotransmitters norepinephrine (NE), DA, and 5-HT in the brains of depressive mice were determined using commercially available kits. In addition, the effects of SJG on the BDNF expression in the mice brain were determined by western blot.Results: Administration of SJG significantly reduced the duration time of immobility in the experiments of FST and TST. In addition, relative to the control mice, SJG (800 mg/kg) administration significantly affected the mobility performance (p < 0.05) of mice. The levels of the three  neurotransmitters (DA, NE and 5-HT) and BDNF in the brains of depressive mice were increased by treatment with SJG at the doses of 200, 400 and 800 mg/kg (p < 0.05). The results suggested that SJG exerted a significant antidepressant effect, which could be attributed to increases in the levels of neurotransmitters, and the up-regulation of BDNF expression.Conclusion: The results suggested that SJG exerted a significant antidepressant effect, most probably via regulation of related neurotransmitters (including DA, NE, and 5-HT) and BDNF in the brain. Keywords: Shu-Gan-Jie-Yu granule, Antidepressant, dopamine, norepinephrine, 5-hydroxytryptamine, brain-derived neurotrophic factor

scholarly journals Beneficial Effects of Crocin against Depression via Pituitary Adenylate Cyclase-Activating Polypeptide

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Linyu Lu ◽  
Die Wu ◽  
Kai Wang ◽  
Juanjuan Tang ◽  
Gang Chen
Keyword(s):  
Adenylate Cyclase ◽  
Pc12 Cells ◽  
Neuroprotective Effect ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Adenosine Monophosphate ◽  
Underlying Mechanism ◽  
Antidepressant Effect ◽  
Mild Stress ◽  
Pituitary Adenylate Cyclase

Depression is one of the foremost psychological illness, and the exact mechanism is unclear. Recent studies have reported that the pituitary adenylate cyclase-activating polypeptide (PACAP) signaling pathway is involved in the progression of depression. In the present study, we extracted crocin from the traditional Chinese medicine (TCM), Gardenia jasminoides Ellis, to evaluate its antidepressant effect and clarify the underlying mechanism. Here, we established a chronic unpredictable mild stress (CUMS) mouse model to assess whether crocin can improve depression-like behavior in an open field test (OFT), tail suspension test (TST), forced swimming test (FST), and sucrose preference test (SPT). A corticosterone (CORT) model of PC12 was set up to explore the antidepressant mechanism of crocin. We pretreated PC12 cells with crocin for 1 hour and then stimulated the cells with CORT for 24 hours. Cell survival was detected by Hoechst staining and MTT assay. The expression of PACAP, cyclic adenosine monophosphate (cAMP) response element binding protein (CREB), and extracellular regulated protein kinases (ERK) were analyzed by western blotting. PACAP RNAi was used to interfere with PC12 cells to downregulate the content of PACAP. The results showed that crocin (30 mg/kg) significantly reversed the decrease of body weight and elevation of serum CORT, mitigated CUMS induced depression-like behaviors of mice, and crocin (12.5 μmol/L) protected PC12 cells against CORT (200 μmol/L)-induced injury. Furthermore, crocin greatly increased the protein expression of PACAP and phosphorylation of ERK and CREB in the CORT model. PACAP RNAi cancelled the neuroprotective effect of crocin. In conclusion, these results indicated that crocin exerted an antidepressant effect via upregulating PACAP and its downstream ERK and CREB signaling pathways.

scholarly journals Aerobic Exercise Prevents Depression via Alleviating Hippocampus Injury in Chronic Stressed Depression Rats

2020 ◽  
Vol 11 (1) ◽  
pp. 9
Author(s):  
Jie Kang ◽  
Di Wang ◽  
Yongchang Duan ◽  
Lin Zhai ◽  
Lin Shi ◽  
...  
Keyword(s):  
Aerobic Exercise ◽  
Mild Stress ◽  
Glutamatergic System ◽  
Sprague Dawley ◽  
Bdnf Expression ◽  
Sprague Dawley Rats ◽  
Immobility Time ◽  
Neurotoxic Effects ◽  
Swimming Test ◽  
Underlying Mechanisms

(1) Background: Depression is one of the overwhelming public health problems. Alleviating hippocampus injury may prevent depression development. Herein, we established the chronic unpredictable mild stress (CUMS) model and aimed to investigate whether aerobic exercise (AE) could alleviate CUMS induced depression-like behaviors and hippocampus injury. (2) Methods: Forty-eight healthy male Sprague-Dawley rats (200 ± 20 g) were randomly divided into 4 groups (control, CUMS, CUMS + 7 days AE, CUMS + 14 days AE). Rats with AE treatments were subjected to 45 min treadmill per day. (3) Results: AE intervention significantly improved CUMS-induced depressive behaviors, e.g., running square numbers and immobility time assessed by the open field and forced swimming test, suppressed hippocampal neuron apoptosis, reduced levels of phosphorylation of NMDA receptor and homocysteine in hippocampus, as well as serum glucocorticoids, compared to the CUMS rats. In contrast, AE upregulated phosphorylation of AMPAR receptor and brain-derived neurotrophic factor (BDNF) hippocampus in CUMS depression rats. The 14 day-AE treatment exhibited better performance than 7 day-AE on the improvement of the hippocampal function. (4) Conclusion: AE might be an efficient strategy for prevention of CUMS-induced depression via ameliorating hippocampus functions. Underlying mechanisms may be related with glutamatergic system, the neurotoxic effects of homocysteine, and/or influences in glucocorticoids-BDNF expression interaction.

scholarly journals lncRNA CASC19 Contributes to Radioresistance of Nasopharyngeal Carcinoma by Promoting Autophagy via AMPK-mTOR Pathway

2021 ◽  
Vol 22 (3) ◽  
pp. 1407
Author(s):  
Hongxia Liu ◽  
Wang Zheng ◽  
Qianping Chen ◽  
Yuchuan Zhou ◽  
Yan Pan ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Cell Line ◽  
Malignant Tumors ◽  
Underlying Mechanism ◽  
Mtor Pathway ◽  
Rna Seq ◽  
Cellular Autophagy ◽  
First Time

Nasopharyngeal carcinoma (NPC) is one of the most frequent head and neck malignant tumors and is majorly treated by radiotherapy. However, radiation resistance remains a serious obstacle to the successful treatment of NPC. The aim of this study was to discover the underlying mechanism of radioresistance and to elucidate novel genes that may play important roles in the regulation of NPC radiosensitivity. By using RNA-seq analysis of NPC cell line CNE2 and its radioresistant cell line CNE2R, lncRNA CASC19 was screened out as a candidate radioresistance marker. Both in vitro and in vivo data demonstrated that a high expression level of CASC19 was positively correlated with the radioresistance of NPC, and the radiosensitivity of NPC cells was considerably enhanced by knockdown of CASC19. The incidence of autophagy was enhanced in CNE2R in comparison with CNE2 and another NPC cell line HONE1, and silencing autophagy with LC3 siRNA (siLC3) sensitized NPC cells to irradiation. Furthermore, CASC19 siRNA (siCASC19) suppressed cellular autophagy by inhibiting the AMPK/mTOR pathway and promoted apoptosis through the PARP1 pathway. Our results revealed for the first time that lncRNA CASC19 contributed to the radioresistance of NPC by regulating autophagy. In significance, CASC19 might be a potential molecular biomarker and a new therapeutic target in NPC.

Nitric oxide mediates the antidepressant-like effect of modafinil in mouse forced swimming and tail suspension tests

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Hossein Omidi-Ardali ◽  
Abolfazl Ghasemi Badi ◽  
Elham Saghaei ◽  
Hossein Amini-Khoei
Keyword(s):  
Nitric Oxide ◽  
Effective Dose ◽  
Animal Studies ◽  
Tail Suspension Test ◽  
Forced Swimming ◽  
Antidepressant Effect ◽  
Tail Suspension ◽  
Immobility Time ◽  
Swimming Test ◽  
Underlying Mechanisms

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.

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