scholarly journals Repurposing of the Nootropic Drug Vinpocetine as an Analgesic and Anti-Inflammatory Agent: Evidence in a Mouse Model of Superoxide Anion-Triggered Inflammation

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Yuri Lourenco-Gonzalez ◽  
Victor Fattori ◽  
Talita P. Domiciano ◽  
Ana C. Rossaneis ◽  
Sergio M. Borghi ◽  
...  
Keyword(s):  
Mouse Model ◽  
Mrna Expression ◽  
Superoxide Anion ◽  
Spontaneous Pain ◽  
Direct Role ◽  
Superoxide Anion Production ◽  
Nootropic Drug ◽  
Potassium Superoxide ◽  
Anti Inflammatory ◽  
Endogenous Antioxidant

Clinically active drugs for the treatment of acute pain have their prescription limited due to the significant side effects they induce. An increase in reactive oxygen species (ROS) has been linked to several conditions, including inflammation and pain processing. Therefore, new or repurposed drugs with the ability of reducing ROS-triggered responses are promising candidates for analgesic drugs. Vinpocetine is a clinically used nootropic drug with antioxidant, anti-inflammatory, and analgesic properties. However, the effects of vinpocetine have not been investigated in a model with a direct relationship between ROS, inflammation, and pain. Based on that, we aimed to investigate the effects of vinpocetine in a model of superoxide anion-induced pain and inflammation using potassium superoxide (KO2) as a superoxide anion donor to trigger inflammation and pain. In the KO2 model, vinpocetine dose-dependently reduced pain-like behaviors (spontaneous pain and hyperalgesia), paw edema, and neutrophil and mononuclear cell recruitment to the paw skin (assessed by H&E staining, fluorescence, and enzymatic assays) and to the peritoneal cavity. Vinpocetine also restored tissue endogenous antioxidant ability and Nrf2 and Ho-1 mRNA expression and reduced superoxide anion production and gp91phox mRNA expression. We also observed the inhibition of IκBα degradation by vinpocetine, which demonstrates a reduction in the activation of NF-κB explaining the diminished production of IL-33, IL-1β, and TNF-α. Collectively, our data show that vinpocetine alleviates pain and inflammation induced by KO2, which is a mouse model with a direct role of ROS in triggering pain and other inflammatory phenomena. Thus, the results suggest the repurposing of vinpocetine as an anti-inflammatory and analgesic drug.

scholarly journals Effects of PDE4 inhibitors on lipopolysaccharide-induced priming of superoxide anion production from human mononuclear cells

2001 ◽  
Vol 10 (3) ◽  
pp. 117-123 ◽  
Author(s):  
Noëlla Germain ◽  
Marianne Corbel ◽  
Chantal Belleguic ◽  
Elisabeth Boichot ◽  
Vincent Lagente
Keyword(s):  
Cyclic Amp ◽  
Superoxide Anion ◽  
Mononuclear Cells ◽  
Adenosine Monophosphate ◽  
Interleukin 10 ◽  
Superoxide Anion Production ◽  
Peripheral Blood Mononuclear ◽  
Human Mononuclear Cells ◽  
Anion Production ◽  
Anti Inflammatory

Aims: Phosphodiesterase 4 (PDE4) inhibitors have been described as potent anti-inflammatory compounds, involving an increase in intracellular levels of cyclic 3',5'-adenosine monophosphate (AMP). The aim of this study was to compare the effects of selective PDE4 inhibitors, rolipram and RP 73-401 with the cell permeable analogue of cyclic AMP, dibutyryl-cyclic AMP (db-cAMP) and the anti-inflammatory cytokine interleukin-10 (IL-10) on superoxide anion production from peripheral blood mononuclear cells preincubated with lipopolysaccharide (LPS).Major findings: We report that, after incubation of the cells with LPS, a large increase in superoxide anion production was observed. Rolipram or RP 73-401 (10-8to 10-5M) induced significant reductions of fMLP-induced superoxide anion production in cells incubated with or without LPS. The db-cAMP (10-5to 10-3M) also elicited dose-dependent inhibitions of the fMLP-induced superoxide anion production. In contrast, IL-10 (1 or 10 ng/ml) did not elicit a reduction in fMLP-induced superoxide anion production in both conditions.Principal conclusion: These results suggest that the inhibitory activity of PDE4 inhibitors on fMLPinduced production of superoxide anion production is mediated by db-cAMP rather than IL-10.

scholarly journals New Anti-Inflammatory Aporphine and Lignan Derivatives from the Root Wood of Hernandia nymphaeifolia

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2286 ◽  
Author(s):  
Chuan-Yen Wei ◽  
Shih-Wei Wang ◽  
Jin-Wang Ye ◽  
Tsong-Long Hwang ◽  
Ming-Jen Cheng ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Superoxide Anion ◽  
Cytochalasin B ◽  
Human Neutrophils ◽  
Superoxide Anion Production ◽  
Natural Sources ◽  
Spectroscopic Analyses ◽  
Anion Production ◽  
Ic50 Values ◽  
Anti Inflammatory

A new aporphine, 3-hydroxyhernandonine (1) and a new lignin, 4′-O-demethyl-7-O-methyldehydropodophyllotoxin (2), have been isolated from the root wood of Hernanadia nymphaeifolia, together with thirteen known compounds (3–15). The structures of these compounds were determined through mass spectrometry (MS) and spectroscopic analyses. The known isolate, 2-O-methyl-7-oxolaetine (3), was first isolated from natural sources. Among the isolated compounds, 3-hydroxyhernandonine (1), 4′-O-demethyl-7-O-methyldehydropodophyllotoxin (2), hernandonine (4), oxohernangerine (5), and oxohernagine (6) displayed inhibition (IC50 values ≤5.72 μg/mL) of superoxide anion production by human neutrophils in response to formyl-l-methionyl-l-leucyl-l-phenylalanine/cytochalasin B (fMLP/CB). In addition, 3-hydroxyhernandonine (1), 4′-O-demethyl-7-O-methyldehydropodophyllotoxin (2), oxohernangerine (5), and oxohernagine (6) suppressed fMLP/CB-induced elastase release with IC50 values ≤5.40 μg/mL.

Role of antioxidant activity of taurine in diabetesThis article is one of a selection of papers from the NATO Advanced Research Workshop on Translational Knowledge for Heart Health (published in part 1 of a 2-part Special Issue).

2009 ◽  
Vol 87 (2) ◽  
pp. 91-99 ◽  
Author(s):  
Stephen W. Schaffer ◽  
Junichi Azuma ◽  
Mahmood Mozaffari
Keyword(s):  
Antioxidant Activity ◽  
Respiratory Chain ◽  
Superoxide Anion ◽  
Hypochlorous Acid ◽  
Antioxidant Defenses ◽  
Ros Generation ◽  
Superoxide Anion Production ◽  
Taurine Deficiency ◽  
Respiratory Chain Activity ◽  
Endogenous Antioxidant

The unifying hypothesis of diabetes maintains that reactive oxygen species (ROS) generated in the mitochondria of glucose-treated cells promote reactions leading to the development of diabetic complications. Although the unifying hypothesis attributes the generation of oxidants solely to impaired glucose and fatty acid metabolism, diabetes is also associated with a decline in the levels of the endogenous antioxidant taurine in a number of tissues, raising the possibility that changes in taurine status might also contribute to the severity of oxidant-mediated damage. There is overwhelming evidence that taurine blocks toxicity caused by oxidative stress, but the mechanism underlying the antioxidant activity remains unclear. One established antioxidant action of taurine is the detoxification of hypochlorous acid. However, not all of the antioxidant actions of taurine are related to hypochlorous acid because they are detected in isolated cell systems lacking neutrophils. There are a few studies showing that taurine either modulates the antioxidant defenses or blocks the actions of the oxidants, but other studies oppose this interpretation. Although taurine is incapable of directly scavenging the classic ROS, such as superoxide anion, hydroxyl radical, and hydrogen peroxide, there are numerous studies suggesting that it is an effective inhibitor of ROS generation. The present review introduces a novel antioxidant hypothesis, which takes into consideration the presence of taurine-conjugated tRNAs in the mitochondria. Because tRNA conjugation is required for normal translation of mitochondrial-encoded proteins, taurine deficiency reduces the expression of these respiratory chain components. As a result, flux through the electron transport chain decreases. The dysfunctional respiratory chain accumulates electron donors, which divert electrons from the respiratory chain to oxygen, forming superoxide anion in the process. Restoration of taurine levels increases the levels of conjugated tRNA, restores respiratory chain activity, and increases the synthesis of ATP at the expense of superoxide anion production. The importance of this and other actions of taurine in diabetes is discussed.

scholarly journals Tempol, a Superoxide Dismutase Mimetic Agent, Inhibits Superoxide Anion-Induced Inflammatory Pain in Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Catia C. F. Bernardy ◽  
Ana C. Zarpelon ◽  
Felipe A. Pinho-Ribeiro ◽  
Cássia Calixto-Campos ◽  
Thacyana T. Carvalho ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Superoxide Dismutase ◽  
Mrna Expression ◽  
Inflammatory Pain ◽  
Superoxide Anion ◽  
Thermal Hyperalgesia ◽  
Mechanical Hyperalgesia ◽  
Antioxidant Defenses ◽  
Paw Edema ◽  
Anti Inflammatory

The present study evaluated the anti-inflammatory and analgesic effects of the superoxide dismutase mimetic agent tempol in superoxide anion-induced pain and inflammation. Mice were treated intraperitoneally with tempol (10–100 mg/kg) 40 min before the intraplantar injection of a superoxide anion donor, potassium superoxide (KO2, 30 μg). Mechanical hyperalgesia and thermal hyperalgesia, paw edema, and mRNA expression of peripheral and spinal cord mediators involved in inflammatory pain, TNFα, IL-1β, IL-10, COX-2, preproET-1, gp91phox, Nrf2, GFAP, and Iba-1, were evaluated. Peripheral and spinal cord reductions of antioxidant defenses and superoxide anion were also assessed. Tempol reduced KO2-induced mechanical hyperalgesia and thermal hyperalgesia and paw edema. The increased mRNA expression of the evaluated mediators and oxidative stress in the paw skin and spinal cord and increased mRNA expression of glial markers in the spinal cord induced by KO2 were successfully inhibited by tempol. KO2-induced reduction in Nrf2 mRNA expression in paw skin and spinal cord was also reverted by tempol. Corroborating the effect of tempol in the KO2 model, tempol also inhibited carrageenan and CFA inflammatory hyperalgesia. The present study demonstrates that tempol inhibits superoxide anion-induced molecular and behavioral alterations, indicating that tempol deserves further preclinical studies as a promising analgesic and anti-inflammatory molecule for the treatment of inflammatory pain.

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