ERK1/2 phosphorylation is involved in the antidepressant-like action of 2,5-diphenyl-3-(4-fluorophenylseleno)-selenophene in mice

Gai, Bibiana Mozzaquatro; Sanna, Maria Domenica; Stein, André L.; Zeni, Gilson; Galeotti, Nicoletta; Nogueira, Cristina W.

doi:10.1016/j.ejphar.2014.04.033

Cited by 9 publications

(2 citation statements)

References 43 publications

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“…Rats undergoing long-term corticosterone treatment showed decreased phosphorylation of ErK1/2 in the hippocampus, suggesting a possible role of ErK1/ErK2 in stress and depression (Gourley et al, 2008;Gai et al, 2014;Leem et al, 2014;Wang et al, 2014). Moreover, Shp-2 was found to play an important role in microglial activation.…”

Section: Discussionmentioning

confidence: 98%

The neuroprotective effects and possible mechanism of action of a methanol extract from Asparagus cochinchinensis: In vitro and in vivo studies

et al. 2016

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Extracts of Asparagus cochinchinensis (AC) have antitumor, anti-inflammatory, and immunostimulant effects. The neurobiological mechanisms underlying the effects of AC have not been sufficiently explored. Thus we performed in vivo and in vitro experiments to further characterize potential therapeutic effects and to clarify the underlying mechanisms. In the tail suspension test immobility time was significantly reduced after administration of AC which suggests antidepressant-like activity without effect on body core temperature. Moreover, in animals pretreated with AC infarct size after occlusion of the middle cerebral artery was reduced. In vitro experiments confirmed neuroprotective effects. Total saponin obtained from AC significantly inhibited H2O2-induced cell death in cultured cortical neurons. The survival-promoting effect by AC saponins was partially blocked by inhibitors for extracellular signal-regulated kinase (ErK) and phosphoinositide 3-kinase Akt (PI3K/Akt) cascades, both of which are known as survival-promoting signaling molecules. Furthermore, phosphorylation of Scr homology-2 (SH2) domain-containing phosphatase 2 (Shp-2) was induced by AC, and the protective effect of AC was abolished by NSC87877, an inhibitor for Shp-2, suggesting an involvement of Shp-2 mediated intracellular signaling in AC saponins. Moreover, AC-induced activation of pShp-2 and ErK1/2 were blocked by NSC87877 indicating that activation of these signaling pathways was mediated by the Shp-2 signaling pathway. These effects appear to be associated with activation of the Shp-2, ErK1/2 and Akt signaling pathways. Our results suggest that AC has antidepressant-like and neuroprotective (reducing infarct size) effects and that activation of pShp-2 and pErK1/2 pathways may be involved in the effects.

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Section: Discussionmentioning

confidence: 98%

The neuroprotective effects and possible mechanism of action of a methanol extract from Asparagus cochinchinensis: In vitro and in vivo studies

et al. 2016

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“…In this context, selenophenes and their derivatives have been widely studied due to their intrinsic biological activity [22], such as antidepressant [23][24][25][26][27][28], antioxidant [29][30][31][32][33][34][35], anticonvulsant [36,37], antibacterial [38], antitumor [39][40][41][42][43][44][45][46][47], antinociceptive [48], hepatoprotective [49,50] and antiapoptotic agents [51]. Besides, they have also played an important role in the materials science field, being used to build organic light emitting diodes (OLEDs) [52][53][54][55][56][57][58], organic field effect transistors (OFETs) [59][60][61][62][63][64][65][66][67][68]…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in the Synthesis of Selenophenes and Their Derivatives

et al. 2020

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The selenophene derivatives are an important class of selenium-based heterocyclics. These compounds play an important role in prospecting new drugs, as well as in the development of new light-emitting materials. During the last years, several methods have been emerging to access the selenophene scaffold, employing a diversity of cyclization-based synthetic strategies, involving specific reaction partners and particularities. This review presents a comprehensive discussion on the recent advances in the synthesis of selenophene-based compounds, starting from different precursors, highlighting the main differences, the advantages, and limitations among them.

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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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ERK1/2 phosphorylation is involved in the antidepressant-like action of 2,5-diphenyl-3-(4-fluorophenylseleno)-selenophene in mice

Cited by 9 publications

References 43 publications

The neuroprotective effects and possible mechanism of action of a methanol extract from Asparagus cochinchinensis: In vitro and in vivo studies

The neuroprotective effects and possible mechanism of action of a methanol extract from Asparagus cochinchinensis: In vitro and in vivo studies

Recent Advances in the Synthesis of Selenophenes and Their Derivatives

Toxicology and pharmacology of synthetic organoselenium compounds: an update

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