Agomelatine, a MT1/MT2 melatonergic receptor agonist with serotonin 5-HT2C receptor antagonistic properties, suppresses Prevotella intermedia lipopolysaccharide-induced production of proinflammatory mediators in murine macrophages

Hyeon, Jin-Yi; Choi, Eun‐Young; Choe, So-Hui; Park, Hae Ryoun; Choi, Jeomil; Choi, Inhee; Kim, Sung-Jo

doi:10.1016/j.archoralbio.2017.05.015

Cited by 10 publications

(4 citation statements)

References 54 publications

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“…The fact that inflammatory macrophages promote development of diabetic encephalopathy suggests a bidirectional relationship between inflammation and T2DM . Agomelatine was found to down‐regulate significantly the generation of proinflammatory mediators as well as the expression of their mRNAs including IL‐1β in macrophages . According to these results, we hypothesized that agomelatine may exert its antidepressive and antiencephalopathic effects in diabetes by modulating proinflammatory factors.…”

Section: Introductionmentioning

confidence: 90%

Agomelatine pretreatment prevents development of hyperglycemia and hypoinsulinemia in streptozotocin‐induced diabetes in mice

Ozcan

Canpolat

Bulmuş

et al. 2018

Fundamemntal Clinical Pharma

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The main objective of this study was to investigate potential effectiveness of agomelatine pretreatment in the prevention of diabetes itself and encephalopathy, with a focus on brain tissue oxidative stress and inflammatory processes in streptozotocin (STZ)-induced diabetic mice. Interleukine-1β (IL-1β) and TACR1 (NK1), which is a tachykinine receptor, were used for the investigation of inflammation in the brain regions including raphe nucleus, periaqueductal gyrus (PAG), amygdala, and nucleus accumbens. The effects of agomelatine on total antioxidant capacity were also evaluated. In the in vitro part of the study, the effects of agomelatine on cell viability were investigated in dorsal root ganglion (DRG) neurons. Fasting blood glucose levels were measured 72 h after STZ injection to determine the diabetic condition. Agomelatine pretreatment prevented both hyperglycemia and hypoinsulinemia in STZ-treated mice. When STZ was injected to induce diabetes in mice, neither hyperglycemia nor hypoinsulinemia was developed in agomelatine pretreated mice and 6 weeks after development of diabetes, agomelatine treatment significantly decreased levels of IL-1β mRNA in raphe nucleus and nucleus accumbens. TACR1 mRNA levels were lower in raphe nucleus, PAG, and amygdala of agomelatine-treated diabetic mice. The increase in total antioxidant capacity after agomelatine administration may responsible for its beneficial effect in the prevention of diabetes. We showed that agomelatine reversed high glucose-induced cell viability decreases in DRG neurons. Both the antihyperglycemic and antioxidant effects of agomelatine might have contributed to the DRG neuron viability improvement. In conclusion, agomelatine seems to both prevent development of diabetes and reverse the encephalopathic changes caused by diabetes.

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Section: Introductionmentioning

confidence: 90%

Agomelatine pretreatment prevents development of hyperglycemia and hypoinsulinemia in streptozotocin‐induced diabetes in mice

Ozcan

Canpolat

Bulmuş

et al. 2018

Fundamemntal Clinical Pharma

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“…The NF-κB protein family plays an important role in the expression of several proinflammatory genes as a key transcription factor. Regulation of this pathway by bioactive substances may be a potential solution for treating inflammatory diseases [44]. NF-κB is a key mediator of chronic stress-induced depression-like behaviors [45].…”

Section: Plos Onementioning

confidence: 99%

Agomelatine prevented depression in the chronic restraint stress model through enhanced catalase activity and halted oxidative stress

Xu,

Zhu,

Jin

et al. 2024

PLoS ONE

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Background Agomelatine (AGO) is an antidepressant with unique pharmacological effects; however, its underlying mechanisms remain unknown. In this study, we examined agomelatine’s effects on catalase activity, oxidative stress, and inflammation. Methods Chronic restraint stress (CRS) model mice were established over 4 weeks, and AGO 50 mg/kg was administered to different groups alongside a deferasirox (DFX) 10 mg/kg gavage treatment. Behavioral tests were performed to assess the effect of AGO on the remission of depression-like behaviors. Meanwhile, the expression of CAT, the oxidative stress signaling pathway and inflammatory protein markers were assessed using ELISA, qRT-PCR, Western blot, and immunohistochemistry. Results Four weeks of AGO treatment significantly improved depression-like behavior in mice through the activation of catalase in the hippocampus and serum of the model mice, increased superoxide dismutase expression, reduced malondialdehyde expression, and reduced oxidative stress damage. Deferasirox was found to offset this therapeutic effect partially. In addition, the inflammatory pathway (including nuclear factor-κB and nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha) was not significantly altered. Conclusions AGO can exert antidepressant effects by altering oxidative stress by modulating catalase activity.

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“…Agomelatine decreases production of interleukin-1-beta (IL-1-beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha), the main mediators of the "cytokine storm" and septic shock). It also depresses the activity of NLRP3 inflammasome, induces autologous processes, prevents macrophage infiltration and microglial cell activation, and decreases cell apoptosis by its effect on the NF-kappa-signaling cascade (Molteni et al, 2013;Hyeon et al, 2017;Kalkman & Feuerbach, 2016). It is hypothesized that the above properties may underlie the antidepressive effectiveness of agomelatine against MDEs occurring after COVID-19.…”

Section: Safetymentioning

confidence: 99%

The effectiveness and tolerability of agomelatine in the treatment of depression after COVID-19 infection in Russian daily clinical practice (TELESPHOR study)

Medvedev,

Bogolepova,

Morozov

et al. 2024

Preprint

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Aim: Affective disorders such as depression and anxiety are one of the most prevalent symptoms observed in patients following coronavirus disease 2019 (COVID-19). The aim of the TELESPHOR study was to evaluate the antidepressant effectiveness and tolerability of agomelatine therapy in daily clinical practice in patients with major depressive episodes (MDE) post-COVID-19. Methods: This multicenter, observational study enrolled outpatients aged 18-65 years who experienced an MDE (17 item Hamilton Rating Scale for Depression [HAMD-17] total score of 8-24) within 3 months of laboratory confirmed SARS-CoV-2 infection and who had initiated treatment with agomelatine. Study visits occurred at weeks 2, 4 and 8. The primary outcome was the antidepressant effectiveness of agomelatine assessed by change in HAMD-17 total score at week 8. Secondary outcomes included changes in HAMD-17 item 10 (anxiety psychic) and item 11 (anxiety somatic), the proportion of responders (≥50% decrease in baseline HAMD-17) and remitters (HAMD-17 score ≤7 at week 8), and impact on quality of life (QoL) (Short Form Survey [SF-36] questionnaire). Tolerability was assessed at each study visit. Results: The full analysis set comprised 103 patients of whom 73 (70.9%) were women. Median age was 45 years, and in the past 3 months 81 (78.6%) had experienced mild and 22 (21.4%) moderate COVID-19. The mean time from onset of infection to study inclusion was 2.1±0.7 months. At study entry, 55 (53.4%) had mild and 48 (46.6%) had moderate MDE. Agomelatine was associated with a significant improvement in depression severity with decreases in mean total HAMD-17 score compared with baseline of 2.6±3.3, 6.7±5.3, and 10.9±4.9 at weeks 2, 4, and 8, respectively (P<0.0001 for all). Significant reductions in anxiety psychic and anxiety somatic were also observed. Mental and physical components of SF-36 were significantly improved compared with baseline (P<0.0001). The proportion of responders was 81.4% and the proportion of remitters was 71.6%. Agomelatine was well tolerated over the 8-week follow-up. Conclusion: Treatment with agomelatine was associated with rapid and significant antidepressive and anxiolytic effectiveness, improved QoL, and good tolerability in the treatment of patients with an MDE after COVID-19.

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Agomelatine, a MT1/MT2 melatonergic receptor agonist with serotonin 5-HT2C receptor antagonistic properties, suppresses Prevotella intermedia lipopolysaccharide-induced production of proinflammatory mediators in murine macrophages

Cited by 10 publications

References 54 publications

Agomelatine pretreatment prevents development of hyperglycemia and hypoinsulinemia in streptozotocin‐induced diabetes in mice

Agomelatine pretreatment prevents development of hyperglycemia and hypoinsulinemia in streptozotocin‐induced diabetes in mice

Agomelatine prevented depression in the chronic restraint stress model through enhanced catalase activity and halted oxidative stress

The effectiveness and tolerability of agomelatine in the treatment of depression after COVID-19 infection in Russian daily clinical practice (TELESPHOR study)

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