The β<sub>2</sub>-adrenoceptor agonist clenbuterol reduces the neuroinflammatory response, neutrophil infiltration and apoptosis following intra-striatal IL-1β administration to rats

Griffin, Éadaoin W.; Yssel, Justin; O’Neill, Eoin; Ryan, Katie J.; Boyle, Noreen; Harper, P. A. W.; Harkin, Andrew; Connor, Thomas J.

doi:10.1080/08923973.2017.1418882

Cited by 12 publications

(10 citation statements)

References 42 publications

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“…Inflammatory cytokines are now considered as important pro-apoptotic factors involved in the progression of neurological disorders (59). For example, intra-striatal IL-1β administration in rats, which triggers inflammatory responses, is subsequently accompanied with increased apoptosis 24 h post-injection, an effect which then promotes brain injury (60). In the present study, we found that the depression-like symptoms observed in rats following chronic stress were accompanied by a marked increasing in neuronal apoptosis within vmPFC regions.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Neuroprotective Effects of Ginsenoside-Rg1 Against Depression-Like Behaviors via Suppressing Glial Activation, Synaptic Deficits, and Neuronal Apoptosis in Rats

et al. 2018

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Depression is considered a neuropsychiatric disease associated with various neuronal changes within specific brain regions. We previously reported that ginsenoside-Rg1, a potential neuroprotective agent extracted from ginseng, significantly alleviated depressive-like disorders induced by chronic stress in rats. However, the mechanisms by which ginsenoside-Rg1 exerts its neuroprotective effects in depression remain largely uncharacterized. In the present study we confirm that ginsenoside-Rg1 significantly prevented the antidepressant-like effects in a rat model of chronic unpredictable mild stress (CUMS) and report on some of the underlying mechanisms associated with this effect. Specifically, we found that chronic pretreatment with ginsenoside-Rg1 prior to stress exposure significantly suppressed inflammatory pathway activity via alleviating the overexpression of proinflammatory cytokines and the activation of microglia and astrocytes. These effects were accompanied with an attenuation of dendritic spine and synaptic deficits as associated with an upregulation of synaptic-related proteins in the ventral medial prefrontal cortex (vmPFC). In addition, ginsenoside-Rg1 inhibited neuronal apoptosis induced by CUMS exposure, increased Bcl-2 expression and decreased cleaved Caspase-3 and Caspase-9 expression within the vmPFC region. Furthermore, ginsenoside-Rg1 could increase the nuclear factor erythroid 2-related factor (Nrf2) expression and inhibit p38 mitogen-activated protein kinase (p-p38 MAPK) and nuclear factor κB (NF-κB) p65 subunit activation within the vmPFC. Taken together, these results suggest that the neuroprotective effects of ginsenoside-Rg1, which may assume the antidepressant-like effect in this animal model of depression, appears to result from amelioration of a CUMS-dependent neuronal deterioration within the vmPFC. Moreover, they also provide support for the therapeutic potential of ginsenoside-Rg1 in the treatment of stress-related mental disorders.

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Section: Discussionmentioning

confidence: 99%

RETRACTED: Neuroprotective Effects of Ginsenoside-Rg1 Against Depression-Like Behaviors via Suppressing Glial Activation, Synaptic Deficits, and Neuronal Apoptosis in Rats

et al. 2018

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“…Our most recent data support this potential hypothesis [9]. Additionally, neutrophils are the innate immune response and thus, neutrophilic infiltration of tissues is involved in many inflammatory diseases [18,19]. In order to inhibit the neutrophilic infiltration from tissue injury (I/R injury, brain injury, ethanol feeding-induced liver injury), several inhibitors such as MgIG (Magnesium isoglycyrrhizinate), Clenbuterol, Phillyrin, or PAI-1 (Plasminogen activator inhibitor-1) have been widely studied [20,21].…”

Section: Discussionsupporting

confidence: 68%

Effects of Kav001 (A Kavain Analogue) on LPS-Induced Cytokines and Neutrophil Infiltration

Tang¹,

Alasiri

Tang

et al. 2019

LOJPCR

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Recently, we found that Kavain grants small amounts of toxicity to mammalian cells, most likely due to its insoluble chemical structure with hydrophobicity. To address this issue, we designed and synthesized compounds with the basic chemical structure of Kavain with a different number of hydrophilic bonds. One soluble compound (named Kav001) from the Kavain analogue was selected and further confirmed to have a stronger biological function than Kavain by in vitro/in vivo experiments such as CAIA mouse models or endotoxic shock [9]. In this paper, we further found that Kav001 not only inhibits TNF-α, but also IL-1β, IL-6, caspase 1 and neutrophil infiltration. However, this phenomenon cannot be observed when macrophages are treated with LPS plus Kavain. We believe that Kav001 may mediate a novel link between Kav001 and LPS-induced inflammation and may be used as a key inhibitor to LPS-induced inflammation/inflammatory disease. Materials and Methods Animals and cellsWild type mice (8-10 week-old C57BL/6, Jackson Labs) were maintained under strict specific pathogen-free (SPF) conditions. All protocols were approved by the Boston University Institutional Animal Care and Use Committee and were performed in compliance with the relevant animal care and use laws and institutional guidelines. THP-1 cells (TIB-202, ATCC) were cultured in a RPMI-1640 media (Cat#: 11875-093, Life Technologies, NY) with 10% FBS at 37 °C in a 5% CO2 atmosphere. CompoundsCommercial Kavain (Cat#59780, Sigma-Aldrich Co., Natick, MA) and custom synthesized analogue Kav001 (Lot#KB180125, KareBay Biochem, Inc.) were obtained. The analysis of each

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“…Since we were attempting to restore the activities of epinephrine and corticosterone at the basal levels that were completely depleted by AD procedure and provide the additional replenishment for increased levels observed during ozone exposure in SH rats, these relatively high doses were selected. Although these doses are several fold higher than those used therapeutically, these CLEN and DEX concentrations are within the range used in other laboratory rodent studies for the purpose of inducing bronchodilation and immunosuppression, respectively (Griffin et al, 2018;Jonasson et al, 2013).…”

Section: Methodsmentioning

confidence: 85%

Beta-2 Adrenergic and Glucocorticoid Receptor Agonists Modulate Ozone-Induced Pulmonary Protein Leakage and Inflammation in Healthy and Adrenalectomized Rats

Henriquez

Snow

Schladweiler

et al. 2018

Toxicological Sciences

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We have shown that acute ozone inhalation activates sympathetic-adrenal-medullary and hypothalamus-pituitary-adrenal stress axes, and adrenalectomy (AD) inhibits ozone-induced lung injury and inflammation. Therefore, we hypothesized that stress hormone receptor agonists (β2 adrenergic-β2AR and glucocorticoid-GR) will restore the ozone injury phenotype in AD, while exacerbating effects in sham-surgery (SH) rats. Male Wistar Kyoto rats that underwent SH or AD were treated with vehicles (saline + corn oil) or β2AR agonist clenbuterol (CLEN, 0.2 mg/kg, i.p.) + GR agonist dexamethasone (DEX, 2 mg/kg, s.c.) for 1 day and immediately prior to each day of exposure to filtered air or ozone (0.8 ppm, 4 h/day for 1 or 2 days). Ozone-induced increases in PenH and peak-expiratory flow were exacerbated in CLEN+DEX-treated SH and AD rats. CLEN+DEX affected breath waveform in all rats. Ozone exposure in vehicle-treated SH rats increased bronchoalveolar lavage fluid (BALF) protein, N-acetyl glucosaminidase activity (macrophage activation), neutrophils, and lung cytokine expression while reducing circulating lymphocyte subpopulations. AD reduced these ozone effects in vehicle-treated rats. At the doses used herein, CLEN+DEX treatment reversed the protection offered by AD and exacerbated most ozone-induced lung effects while diminishing circulating lymphocytes. CLEN+DEX in air-exposed SH rats also induced marked protein leakage and reduced circulating lymphocytes but did not increase BALF neutrophils. In conclusion, circulating stress hormones and their receptors mediate ozone-induced vascular leakage and inflammatory cell trafficking to the lung. Those receiving β2AR and GR agonists for chronic pulmonary diseases, or with increased circulating stress hormones due to psychosocial stresses, might have altered sensitivity to air pollution.

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The β₂-adrenoceptor agonist clenbuterol reduces the neuroinflammatory response, neutrophil infiltration and apoptosis following intra-striatal IL-1β administration to rats

Cited by 12 publications

References 42 publications

RETRACTED: Neuroprotective Effects of Ginsenoside-Rg1 Against Depression-Like Behaviors via Suppressing Glial Activation, Synaptic Deficits, and Neuronal Apoptosis in Rats

RETRACTED: Neuroprotective Effects of Ginsenoside-Rg1 Against Depression-Like Behaviors via Suppressing Glial Activation, Synaptic Deficits, and Neuronal Apoptosis in Rats

Effects of Kav001 (A Kavain Analogue) on LPS-Induced Cytokines and Neutrophil Infiltration

Beta-2 Adrenergic and Glucocorticoid Receptor Agonists Modulate Ozone-Induced Pulmonary Protein Leakage and Inflammation in Healthy and Adrenalectomized Rats

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The β2-adrenoceptor agonist clenbuterol reduces the neuroinflammatory response, neutrophil infiltration and apoptosis following intra-striatal IL-1β administration to rats

Cited by 12 publications

References 42 publications

RETRACTED: Neuroprotective Effects of Ginsenoside-Rg1 Against Depression-Like Behaviors via Suppressing Glial Activation, Synaptic Deficits, and Neuronal Apoptosis in Rats

RETRACTED: Neuroprotective Effects of Ginsenoside-Rg1 Against Depression-Like Behaviors via Suppressing Glial Activation, Synaptic Deficits, and Neuronal Apoptosis in Rats

Effects of Kav001 (A Kavain Analogue) on LPS-Induced Cytokines and Neutrophil Infiltration

Beta-2 Adrenergic and Glucocorticoid Receptor Agonists Modulate Ozone-Induced Pulmonary Protein Leakage and Inflammation in Healthy and Adrenalectomized Rats

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The β₂-adrenoceptor agonist clenbuterol reduces the neuroinflammatory response, neutrophil infiltration and apoptosis following intra-striatal IL-1β administration to rats