The effects of methylated flavonoids on depression-like activity and pro-inflammatory cytokine thresholds in mice induced by repeated finasteride administration

The aim of the study was to investigate the influence of naringenin (NGN) and its methylated derivatives (50 or 100 mg kg−1) on finasteride-caused depression-like performance in mice to identify the effects on behavior and biomarkers of inflammation in the management of depression. Depression-like behavior was induced by repeated dose of finasteride (100 mg kg−1, subcutaneously) in mice. The effects of the naringenin (50 or 100 mg kg−1) or its methylated derivatives (Ngn-M; 50 or 100 mg kg−1 or Ngn-DM; 50 or 100 mg kg−1) and duloxetine (DXT, 10 mg kg−1) were evaluated for the immobility time in tail suspension and forced swimming tests following finasteride pre-treatment. The levels of brain pro-inflammatory cytokines such as IL-1β and TNF-α were also measured by Enzyme-Linked Immunosorbent Assay to further evaluate the impact of naringenin and its methylated derivatives on inflammation. Pre-treatment with finasteride substantially increased both the immobility time spent in tail suspension and forced swimming tests and brain levels of IL-1β and TNF–α in mice. Doluxetine (DLX) was given at a dose of 10 mg kg−1, and Naringenin or its methylated derivatives were given at doses of 50 and 100 mg kg−1 orally. It reduced immobility time in both tests, restored the preference to sucrose solution, and normalized cytokine levels (p < 0.01) in mice. Similar effects were observed with DTX (10 mg kg−1) as positive control. The increased brain levels of malondialdehyde (MDA) or nitrite were considerably (p < 0.05) decreased while substantially (p < 0.05) increased glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) levels after finasteride pre-treatment relative to vehicle-control by naringenin or its methylated derivatives (50 or 100 mg kg−1). These findings demonstrated the potential for methylated flavonoids as safe and effective anti-depressive agents.

Download Full-text

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

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2020-0021 ◽

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.

Download Full-text

Impact of loganin on pro-inflammatory cytokines and depression- and anxiety-like behaviors in male diabetic rats

Physiology International ◽

10.1556/2060.105.2018.2.8 ◽

2018 ◽

Vol 105 (2) ◽

pp. 116-126 ◽

Cited By ~ 2

Author(s):

M Rajabi ◽

G Mohaddes ◽

F Farajdokht ◽

S Nayebi Rad ◽

M Mesgari ◽

...

Keyword(s):

Body Weight ◽

Blood Glucose ◽

Inflammatory Cytokines ◽

Diabetic Rats ◽

Assay Method ◽

Enzyme Linked Immunosorbent Assay ◽

Depression And Anxiety ◽

Tnf Α ◽

Immobility Time ◽

Pro Inflammatory Cytokines

Behavioral disturbances are observed in most patients suffering from diabetes. According to some evidence, pro-inflammatory cytokines have a key role both in diabetes and behavioral disorders, such as anxiety and depression. In this study, the effect of chronic administration of loganin, as a bioflavonoid, was investigated on pro-inflammatory cytokines and depression- and anxiety-like behaviors in streptozotocin-induced diabetes in male Wistar rats. Blood levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were assessed by enzyme-linked immunosorbent assay method. Depression- and anxiety-like behaviors were evaluated by forced swimming test (FST), elevated plus maze (EPM), and open field test (OFT), respectively. Body weight was also measured before the interventions and after the experiments in all groups. Our findings show that loganin-treated animals had significantly lower serum concentrations of IL-6 and TNF-α compared with the diabetic group. In the EPM test, loganin treatment significantly increased the percentage of the open arm time and open arm entries. Moreover, loganin treatment significantly decreased the grooming time and restored distance traveled and center crossing in the OFT. However, it decreased immobility time in the FST. Loganin treatment also significantly restored body weight gain and attenuated blood glucose changes in the diabetic rats. These results indicate that loganin possibly alleviates depression- and anxiety-like behaviors associated with diabetes through lowering the blood glucose and pro-inflammatory cytokine levels. More research is required to show the exact mechanism of antidepressant and anxiolytic effects of loganin in diabetes.

Download Full-text

Apigenin Acts as Anti-inflammatory Compound through Reducing IL-1β, IL-6 and TNF-α in LPS-induced Inflammation; in-vivo Study

10.21203/rs.3.rs-867818/v1 ◽

2021 ◽

Author(s):

Sanaz Jamshidi ◽

Mohammad Sofiabadi ◽

Mina Eslami ◽

Farshad Foroughi

Keyword(s):

Positive Control ◽

Enzyme Linked Immunosorbent Assay ◽

Tnf Α ◽

Male Wistar Rats ◽

Steroid Drug ◽

Spss Software ◽

Anti Inflammatory ◽

Α Level ◽

Control Sham

Abstract Background: Consumption of herbal flavonoids instead of chemical drugs has increased in recent years due to fewer side effects and affordability. In this study, the effect of apigenin was investigated on inflammation induced by lipopolysaccharide in male rat's serum by measuring the pro-inflammatory cytokines, i.e., IL-1β, IL-6, and TNF-α.Methods: 90 male Wistar rats weighing 200 ±2 grams were used and divided into control, sham (solvent), and positive control (dexamethasone 15 mg/kg. ip), and 3 experimental groups which received 5, 15 or 30 mg/kg of apigenin, intraperitoneally. In 30 minutes after interventions, lipopolysaccharide (LPS) [30 μg/kg. ip] was injected. Then, at 4, 12- and 24-hour intervals, rats were anesthetized, and blood samples were prepared intracardially. Samples were centrifuged, and serums were separated and stored at -80 ° C. Measurement of IL-1β, IL-6, and TNF-α were conducted by the enzyme-linked immunosorbent assay (ELISA) method. Data were analyzed using the SPSS software version 19.Results: Pre-injection of apigenin at 5 mg/kg dosage were reduced TNF-α and IL-1β levels at 24-hours after LPS injection, compared to control (for both P <0.05). Pre-injection of 15 mg/kg of apigenin was reduced IL-6 level at 24-hours after LPS injection (P <0.05). Pre-injection of 30 mg/kg of apigenin were reduced TNF-α level at 4- (P <0.05), 12- (P <0.01) and 24- (P <0.01) hours, IL-1β level at 24-hours (P <0.01), and IL-6 level at 4- (P <0.05) and 24- (P <0.01) hours after LPS injection.Conclusions: Apigenin reduces proinflammatory cytokines in serum in acute inflammation induction. This impact is close to the dexamethasone effect as an anti-inflammatory steroid drug.

Download Full-text

Characterization of the Plasmacytoid Dendritic Cell Response to Transmitted/Founder and Nontransmitted Variants of HIV-1

Journal of Virology ◽

10.1128/jvi.00157-18 ◽

2018 ◽

Vol 92 (19) ◽

Cited By ~ 4

Author(s):

Jordan Ari Schwartz ◽

Hongliang Zhang ◽

Zachary Ende ◽

Martin J. Deymier ◽

Terry Lee ◽

...

Keyword(s):

Dendritic Cell ◽

Plasmacytoid Dendritic Cell ◽

Female Genital Tract ◽

Enzyme Linked Immunosorbent Assay ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

The Impact ◽

Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) infection often arises from a single transmitted/founder (TF) viral variant among a large pool of viruses in the quasispecies in the transmitting partner. TF variants are typically nondominant in blood and genital secretions, indicating that they have unique traits. The plasmacytoid dendritic cell (pDC) is the primary alpha interferon (IFN-α)-producing cell in response to viral infections and is rapidly recruited to the female genital tract upon exposure to HIV-1. The impact of pDCs on transmission is unknown. We investigated whether evasion of pDC responses is a trait of TF viruses. pDCs from healthy donors were stimulated in vitro with a panel of 20 HIV-1 variants, consisting of one TF variant and three nontransmitted (NT) variants each from five transmission-linked donor pairs, and secretion of IFN-α and tumor necrosis factor alpha (TNF-α) was measured by enzyme-linked immunosorbent assay (ELISA). No significant differences in cytokine secretion in response to TF and NT viruses were observed, despite a trend toward enhanced IFN-α and TNF-α production in response to TF viruses. NT viruses demonstrated polarization toward production of either IFN-α or TNF-α, indicating possible dysregulation. Also, for NT viruses, IFN-α secretion was associated with increased resistance of the virus to inactivation by IFN-α in vitro, suggesting in vivo evolution. Thus, TF viruses do not appear to preferentially subvert pDC activation compared to that with nontransmitted HIV-1 variants. pDCs may, however, contribute to the in vivo evolution of HIV-1. IMPORTANCE The plasmacytoid dendritic cell (pDC) is the first cell type recruited to the site of HIV-1 exposure; however, its contribution to the viral bottleneck in HIV-1 transmission has not been explored previously. We hypothesized that transmitted/founder viruses are able to avoid the pDC response. In this study, we used previously established donor pair-linked transmitted/founder and nontransmitted (or chronic) variants of HIV-1 to stimulate pDCs. Transmitted/founder HIV-1, instead of suppressing pDC responses, induced IFN-α and TNF-α secretion to levels comparable to those induced by viruses from the transmitting partner. We noted several unique traits of chronic viruses, including polarization between IFN-α and TNF-α production as well as a strong relationship between IFN-α secretion and the resistance of the virus to neutralization. These data rule out the possibility that TF viruses preferentially suppress pDCs in comparison to the pDC response to nontransmitted HIV variants. pDCs may, however, be important drivers of viral evolution in vivo.

Download Full-text

Alpha-terpineol: evaluation and pharmacological screening as an antidepressant agent

Research Society and Development ◽

10.33448/rsd-v10i11.19571 ◽

2021 ◽

Vol 10 (11) ◽

pp. e191101119571

Author(s):

Amanda Fonseca Costa Assunção ◽

Nícolas Davidson Sérvulo Rodrigues ◽

Andreia Viana da Costa Sampaio ◽

Karolinny dos Santos Silva ◽

Laryssa Roque da Silva ◽

...

Keyword(s):

Motor Coordination ◽

Forced Swimming Test ◽

Open Field Test ◽

Tail Suspension Test ◽

Experimental Tests ◽

Forced Swimming ◽

Tail Suspension ◽

Immobility Time ◽

Swimming Test ◽

Antidepressant Action

Objective: To evaluate the possible antidepressant effects of alpha-terpineol in rodents. Material and Methods: Depression levels were analyzed by comparing the total immobility time presented by the animals of the experimental groups in the test session, using the Forced Swimming Test and the Tail Suspension Test. The parameters of locomotion (central, peripheral and total) and motor coordination were evaluated in the Open Field Test and in the Rota Rod Test, respectively. In the second stage, the involvement of the noradrenergic system in the antidepressant action of alpha-terpineol in Forced Swimming Test was investigated. Results and Discussion: After performing the experimental tests, it was observed that the animals that received alpha-terpineol had reduced immobility time in Forced Swimming Test and Tail Suspension Test, compared to the other groups. In the Open Field Test and Rota-rod, the mice showed, respectively, good exploratory activity and motor coordination during the tests. In addition, the study of the Noradrenergic System proved to be a promising mechanism used during its antidepressant action. Conclusion: In view of the results of the experimental tests, alpha-terpineol presented similar responses to those found in other monoterpenes investigated in the literature. Thus, it is shown as a promising antidepressant to be used clinically in humans, with less side effects and low production cost.

Download Full-text

Impact of loganin on pro-inflammatory cytokines and depression- and anxiety-like behaviors in male diabetic rats

Physiology International ◽

10.1556/2060.105.2018.1.8 ◽

2018 ◽

Vol 105 (3) ◽

pp. 199-209 ◽

Cited By ~ 10

Author(s):

M Rajabi ◽

G Mohaddes ◽

F Farajdokht ◽

S Nayebi Rad ◽

M Mesgari ◽

...

Keyword(s):

Body Weight ◽

Blood Glucose ◽

Inflammatory Cytokines ◽

Diabetic Rats ◽

Assay Method ◽

Enzyme Linked Immunosorbent Assay ◽

Depression And Anxiety ◽

Tnf Α ◽

Immobility Time ◽

Pro Inflammatory Cytokines

Download Full-text

Effects of Electroacupuncture on Chronic Unpredictable Mild Stress Rats Depression-Like Behavior and Expression of p-ERK/ERK and p-P38/P38

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/650729 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 11

Author(s):

Jian Xu ◽

Yanling She ◽

Ning Su ◽

Ruixin Zhang ◽

Lixing Lao ◽

...

Keyword(s):

Forced Swimming Test ◽

Sucrose Solution ◽

Chronic Mild Stress ◽

Forced Swimming ◽

Mild Stress ◽

Chronic Unpredictable Mild Stress ◽

Sprague Dawley ◽

Unpredictable Chronic Mild Stress ◽

Immobility Time ◽

Swimming Test

We investigate the antidepressant-like effect and mechanism of electroacupuncture (EA) on a chronic unpredictable mild stress rats depression-like behavior. In our study, depression in rats was induced by unpredictable chronic mild stress (UCMS) and isolation for four weeks. Male Sprague-Dawley rats were randomly divided into four groups: Normal, Model, EA, and Sham EA. EA treatment was administered for two weeks, once a day for five days a week. Two acupoints, Yintang (EX-HN3) and Baihui (GV20), were selected. For sham EA, acupuncture needles were inserted shallowly into the acupoints: EX-HN3 and GV20. No electrostimulator was connected. The antidepressant-like effect of the electroacupuncture treatment was measured by sucrose intake test, open field test, and forced swimming test in rats. The protein levels of phosphorylated extracellular regulated protein kinases (p-ERK1/2)/ERK1/2 and p-P38/P38 in the hippocampus (HP) were examined by Western blot analysis. Our data demonstrate that EA treatment decreased the immobility time of forced swimming test and improved the sucrose solution intake in comparison to unpredictable chronic mild stress and placebo sham control. Electroacupuncture may act on depression by enhancing p-ERK1/2 and p-p38 in the hippocampus.

Download Full-text

Antidepressant-like Effect of Baccharis Ilimita in the Forced Swimming Test in Mice

European Psychiatry ◽

10.1016/s0924-9338(09)70885-5 ◽

2009 ◽

Vol 24 (S1) ◽

pp. 1-1 ◽

Cited By ~ 1

Author(s):

A. Kikko ◽

P. Koerich ◽

E. Bondan ◽

F. Nunes ◽

M. Pizzolatti ◽

...

Keyword(s):

Secondary Metabolites ◽

Open Field ◽

Leaf Extract ◽

Forced Swimming Test ◽

Positive Control ◽

Forced Swimming ◽

Control Group ◽

Swiss Mice ◽

Immobility Time ◽

Swimming Test

The aim of the present work was to investigate if flowers extract (FE) and leaf extract (LE) of Baccharis ilimita (Asteraceae) induced antidepressant-like effect. Previous phytochemical investigations have shown the presence of structurally and biogenetically diverse secondary metabolites in this gene, such as flavonoids, diterpenes and triterpenes. Male Swiss mice were injected with FE and LE (12.5; 25.0 or 50.0 mg/kg; i.p.) or saline (S) and after 30 min, they were tested in the forced swimming test (FST). The results showed that FE and LE (50 mg/kg) decreased the duration of immobility time in comparison to the control group (S: 114.8s ± 10.23; FE50: 47.52s ± 9.45; LE50: 53.36s ± 10.38). However, the 12.5 and 25.0 mg/kg doses had no effect on the immobility time in comparison to the control group. The FE and LE did not produce any change in ambulation in mice when tested in an open field. The imipramine (IMP; 15.0 mg/kg i.p.) was used as the positive control. Our results suggested that FE and LE of Baccharis ilimita presents antidepressant-like effect in mice. Such results suggest that the antidepressant-like effect may be attributed at lest partially the flavonoids or the interaction of the active(s) principle(s) present in this plant.Descritores:Baccharis ilimita. Forced swimming test. Depression. Mice.

Download Full-text

Antidepresant effects of Cinnamon (Cinnamomum burmannii) extract in depressed induced rats using 3-minutes Tail Suspension method

BioScientia Medicina ◽

10.32539/bsm.v3i3.91 ◽

2019 ◽

Vol 3 (3) ◽

pp. 1-8

Author(s):

Nita Parisa ◽

Mayasari Mayasari ◽

Nia Savitri Tamzil ◽

Bintang Arroyantri ◽

Ziske Maritska

Keyword(s):

Animal Model ◽

Positive Control ◽

Control Group ◽

P Value ◽

Tail Suspension ◽

Treatment Groups ◽

Cinnamon Extract ◽

Immobility Time ◽

Cinnamomum Burmannii ◽

One Way Anova

Abstract Background. The increasing prevalence of depression gives rise to challenges in not only elucidating its diverse causes, but also in finding an effective treatment. One of the factors linked to depression is the imbalance of serotonin, norepinephrine, and dopamine neurotransmitters. Cinnamon (Cinnamomum burmannii) as one of the worldâ€™s wellknown cooking ingredients is believed to be able to regulate the neurotransmitters imbalance with the help of terpenoids and flavonoid polyphenols as one of its content. Objective. This study aims to determine the effectiveness of cinnamon extract as an antidepressant in depressed induced animal model. Methods. An experimental in vivo with pre-post control group design was conducted in twenty five Wistar strain white rats that were divided into 5 treatment groups that received fluoxetine as positive control, aquades, and different dose of cinnamon extracts (50 mg/kgBW, 100 mg/kgBW, and 200 mg/kgBW). Depression induction method used was 3-minute Tail Suspension Test, done for 14 days. The antidepressant effectiveness test was carried out by calculating the immobility time duration with Forced Swimming Test method and was further analyzed using one-way ANOVA test. Results. One-way ANOVA test results showed that there were differences in the mean duration of immobility time between treatment groups after being given cinnamon extract (p value = 0,000). Groups that were given 100 mg/kgBW cinnamon extract and 200 mg /kgBW showed a p value>0.05 when compared with positive control group receiving Fluoxetine although displayed a similar reduced immobility time. Conclusion. Cinnamon (Cinnamomum burmannii) extract showed a promising potential as an effective antidepressant tested in animal model. Keywords: cinnamon, extract, depression, immobility time, rat

Download Full-text

Assessment of the Antioxidant Potential of Hypoestes rosea Leaf in Lead-acetate-induced Albino Rats

Journal of Complementary and Alternative Medical Research ◽

10.9734/jocamr/2020/v9i130135 ◽

2020 ◽

pp. 45-55

Author(s):

F. K. Uwikor ◽

E. O. Nwachuku ◽

F. Igwe ◽

E. S. Bartimaeus

Keyword(s):

Oxidative Stress ◽

Lead Acetate ◽

Positive Control ◽

Post Treatment ◽

Albino Rats ◽

Oxidative Stress Markers ◽

Stress Markers ◽

Pre Treatment ◽

The Impact ◽

Dose Dependent

Hypoestes rosea has been used as a traditional medicine in the Niger delta for dysfunction of the endocrine system. However, there has been no known study on the effects of hypoestes rosea on oxidative stress. In this study we evaluated the effect of aqueous extract of Hypoestes rosea (AEHR) leaf on oxidative stress markers of lead acetate induced male and female albino rats at acute and sub-chronic stages in pre-treatment and post-treatment phases. Animals were divided into 17 groups of five each for both sexes in the treatment groups, while the positive control group had 10 animals in each sex. 8 groups were for the acute phase of the study for 21 days in each sex, while 8 were for 35 days for the sub chronic stage of the study. Negative Control (NC) group received rat feed only, Experimental (EC) group received 100 mg/kg bwt/day for 21 days at acute and 35 days for sub chronic. Positive Control (PC) group received 60mg/kg b.wt per day of lead acetate for 35 days. The other 3 groups received 100 mgkg, 200 mg/kg and 300 mg/kg b. wt respectively for 14 and 28 days either as pre treatment or post treatment, for both sexes of the albino rats. Samples were taken at the end of the study period through the jugular vein under chloroform anaesthesia. Results showed lead acetate induced oxidative stress in the rats, evidenced by the significantly decreased (p < 0.05) Superoxide Dismutase (SOD) and Total Antioxidant Capacity (TAC) between the NC and PC groups. The plant in a dose dependent pattern was able to significantly (p < 0.05), reverse the effect of lead acetate in the Post and pre treatment phases. Our study also shows that dose dependent AEHR extract significantly reduced the impact of lead in oxidative stress markers. In conclusion, consumption of AEHR by albino rats could help protect against lead acetate induced oxidative stress.

Download Full-text