Selanylimidazopyridine Prevents Lipopolysaccharide-Induced Depressive-Like Behavior in Mice by Targeting Neurotrophins and Inflammatory/Oxidative Mediators

Domingues, Micaela; Casaril, Angela Maria; Birmann, Paloma T.; Lourenço, Darling de Andrade; Vieira, Beatriz; Begnini, Karine R.; Lenardão, Eder J.; Collares, Tiago; Seixas, Fabiana Kömmling; Savegnago, Lucielli

doi:10.3389/fnins.2018.00486

Cited by 32 publications

(16 citation statements)

References 45 publications

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“…In the search for new potential antidepressant-like compounds, the same group synthesized and demonstrated the antidepressant activity of another N -heterocycle derivative, 3-(( p -methoxyphenyl)selanyl)-2-phenylimidazo[1,2-a]pyridine (Domingues et al 2018 , 2019 ). Very recently, an isoquinoline derivative has been reported as an antidepressant-like compound that selectively and reversibly inhibited cerebral monoamino oxidase (MAO) B activity in C57Bl/6 mice (Sampaio et al 2016 , 2020 ).…”

Section: Pharmacology Of Organoselenium Compoundsmentioning

confidence: 99%

Toxicology and pharmacology of synthetic organoselenium compounds: an update

2021

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Here, we addressed the pharmacology and toxicology of synthetic organoselenium compounds and some naturally occurring organoselenium amino acids. The use of selenium as a tool in organic synthesis and as a pharmacological agent goes back to the middle of the nineteenth and the beginning of the twentieth centuries. The rediscovery of ebselen and its investigation in clinical trials have motivated the search for new organoselenium molecules with pharmacological properties. Although ebselen and diselenides have some overlapping pharmacological properties, their molecular targets are not identical. However, they have similar anti-inflammatory and antioxidant activities, possibly, via activation of transcription factors, regulating the expression of antioxidant genes. In short, our knowledge about the pharmacological properties of simple organoselenium compounds is still elusive. However, contrary to our early expectations that they could imitate selenoproteins, organoselenium compounds seem to have non-specific modulatory activation of antioxidant pathways and specific inhibitory effects in some thiol-containing proteins. The thiol-oxidizing properties of organoselenium compounds are considered the molecular basis of their chronic toxicity; however, the acute use of organoselenium compounds as inhibitors of specific thiol-containing enzymes can be of therapeutic significance. In summary, the outcomes of the clinical trials of ebselen as a mimetic of lithium or as an inhibitor of SARS-CoV-2 proteases will be important to the field of organoselenium synthesis. The development of computational techniques that could predict rational modifications in the structure of organoselenium compounds to increase their specificity is required to construct a library of thiol-modifying agents with selectivity toward specific target proteins.

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Section: Pharmacology Of Organoselenium Compoundsmentioning

confidence: 99%

Toxicology and pharmacology of synthetic organoselenium compounds: an update

2021

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“…BDNF is a major representative of the brain neurotrophic factors, which are involved in cognition control. Cognitive dysfunction in depressive patients is due to decreased levels of BDNF (Domingues et al, 2018), and BDNF has been suggested to influence the response to antidepressant treatment (Hennings et al, 2019). Therefore, the effect of rhFGF21 on BDNF expression was measured.…”

Section: Exogenous Rhfgf21 Could Function Through Fgfr1 Activationmentioning

confidence: 99%

“…Several hypotheses to explain the pathology of depression, including glutamatergic excitotoxicity, monoamine system impairment, hypothalamic-pituitary-adrenal axis dysfunction, neuroinflammation, and neural plasticity and neurogenesis disruption, have emerged (Taniguti et al, 2019). Among these hypotheses, inflammatory processes have been suggested to be involved in the etiology of depression in many studies (Domingues et al, 2018). Increasing amounts of preclinical and clinical research have shown that proinflammatory cytokines might contribute to depression.…”

Section: Introductionmentioning

confidence: 99%

“…Nuclear factor-kB (NF-kB), a major transcription factor, is involved in the activation of an exceptionally large number of genes in response to inflammation. Once stimulated by LPS, NF-kB translocates to the nucleus and regulates the expression of inflammatory cytokines such as TNF-a, interleukin-1b (IL-1b), and IL-6 (Lin et al, 2007;Domingues et al, 2018;Muhammad et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

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FGF21 Attenuated LPS-Induced Depressive-Like Behavior via Inhibiting the Inflammatory Pathway

Wang

Zhu

et al. 2020

Front. Pharmacol.

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Major depressive disorder is a serious neuropsychiatric disorder with high rates of recurrence and mortality. Many studies have supported that inflammatory processes play a central role in the etiology of depression. Fibroblast growth factor 21 (FGF21), a member of the fibroblast growth factors (FGFs) family, regulates a variety of pharmacological activities, including energy metabolism, glucose and lipid metabolism, and insulin sensitivity. In addition, recent studies showed that the administration of FGF21, a regulator of metabolic function, had therapeutic effects on mood stabilizers, indicating that FGF21 could be a common regulator of the mood response. However, few studies have highlighted the antidepressant effects of FGF21 on lipopolysaccharide (LPS)induced mice, and the anti-inflammatory mechanism of FGF21 in depression has not yet been elucidated. The purpose of the current study was to determine the antidepressant effects of recombinant human FGF21 (rhFGF21). The effects of rhFGF21 on depression-like behaviors and the inflammatory signaling pathway were investigated in both an LPS-induced mouse model and primary microglia in vitro. The current study demonstrated that LPS induced depressive-like behaviors, upregulated proinflammatory cytokines, and activated microglia in the mouse hippocampus and activated the inflammatory response in primary microglia, while pretreatment with rhFGF21 markedly improved depression-like behavior deficits, as shown by an increase in the total distance traveled and number of standing numbers in the open field test (OFT) and a decrease in the duration of immobility in the tail suspension test (TST) and forced swimming test (FST). Furthermore, rhFGF21 obviously suppressed expression levels of the proinflammatory cytokines interleukin-1b (IL-1b), tumor necrosis factor-a (TNF-a), and interleukin-6 (IL-6) and inhibited microglial activation and the nuclear factor-kB (NF-kB) signing pathway. Moreover, coadministration of rhFGF21 with the fibroblast growth factor receptor 1 (FGFR1) inhibitor PD173074 significantly reversed these protective effects, indicating that the antidepressant effects of rhFGF21 occur through FGFR1 activation. Taken together, the results of the current study demonstrated for the first time that exogenous rhFGF21 ameliorated LPS-induced depressive-like behavior by inhibiting microglial Frontiers in Pharmacology | www.frontiersin.org February 2020 | Volume 11 | Article 154 1 expression of proinflammatory cytokines through NF-kB suppression. This new discovery suggests rhFGF21 as a new therapeutic candidate for depression treatment.

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“…Multiple administrations of LPS increase the expression of inflammatory related markers and lead the immune activation and ROS production in brain. These events are reported to accumulate beta amyloids (Aβs) in the cerebral cortex and hippocampus [29]. We found that, LPS-induced mice expressed high levels of malondialdehyde (MDA) that indicated the enhancement of lipid peroxidation and produced oxidative stress in the brain.…”

Section: Discussionmentioning

confidence: 94%

Neuroprotective Potential of Mahanimbine against Lipopolysaccharides (LPS)-Induced Neuronal Deficits on SK-N-SH Cells and Antioxidant Potentials in ICR Mice Brain

Azahan¹,

Mani²,

Ramasamy³

et al. 2019

JPRI

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Aims: Murraya koenigii commonly known as curry leaves, is traditionally used in India and other South Asian countries as a spice for its characteristic flavor and aroma. Mahanimbine is a major carbazole alkaloid derived from Murraya koenigii leaves. There are numerous reports that support the neuroprotective role of various alkaloids. The present study investigated the neuroprotective potential of mahanimbine against lipopolysaccharides (LPS)-induced neuronal deficits of SK-N-SH cells and antioxidant potentials in ICR mouse brain. Study Design: The targeted compound mahanimbine was subjected to both in vitro and in vivo studies. Place and Duration of Study: The study was conducted in Faculty of Pharmacy, Universiti Teknologi MARA, Malaysia and College of Pharmacy, Qassim University, Kingdom of Saudi Arabia between June 2015 and August 2017. Methodology: For the in vitro study, SK-N-SH cells were induced with the 100µg/ml of LPS. Then, neuroprotection and reactive oxygen species (ROS) assays were conducted to assess cell viability and the formation of ROS. On the other hand, ICR mice were being fed with mahanimbine (1, 2 and 5 mg/kg, p.o.) for 30 days for in vivo study. Neuroinflammation was thereafter induced by intraperitoneal injection of LPS (250 μg/kg) for 4 days. At the end of the treatment, the animals were sacrificed. The brain was collected for antioxidants assays, measuring oxidative biomarkers such as catalase, reduced glutathione, superoxide dismutase, glutathione reductase, and thiobarbituric acid (TBARs). Results: SK-N-SH cells exposed to 100 μg/ml LPS showed a significant cell viability loss and increased level of ROS. However, pre-treatment of SK-N-SH cells with mahanimbine significantly prevented cell loss and consequently attenuated LPS-induced ROS formation. In addition, mahanimbine also inhibited β-secretase (BACE50 = 4µg/mL) that is important for production of β-amyloid (Aβ). For in vivo study, the biochemical analysis of the whole brain detected increased catalase (CAT) and glutathione reductase (GRD) levels, and significantly decreased malondialdehyde (MDA) level in mahanimbine treated groups as compared to LPS-induced but untreated group. Conclusion: The overall findings supported the neuroprotective and antioxidant potential of mahanimbine against LPS-induced neurotoxicity.

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Selanylimidazopyridine Prevents Lipopolysaccharide-Induced Depressive-Like Behavior in Mice by Targeting Neurotrophins and Inflammatory/Oxidative Mediators

Cited by 32 publications

References 45 publications

Toxicology and pharmacology of synthetic organoselenium compounds: an update

Toxicology and pharmacology of synthetic organoselenium compounds: an update

FGF21 Attenuated LPS-Induced Depressive-Like Behavior via Inhibiting the Inflammatory Pathway

Neuroprotective Potential of Mahanimbine against Lipopolysaccharides (LPS)-Induced Neuronal Deficits on SK-N-SH Cells and Antioxidant Potentials in ICR Mice Brain

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