Tag: Attenuates

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Ponciretin attenuates ethanol-induced gastric damage in mice by inhibiting inflammatory responses.

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Ponciretin attenuates ethanol-induced gastric damage in mice by inhibiting inflammatory responses.

Int Immunopharmacol. 2016 Dec 22;43:179-186

Authors: Kang GD, Kim DH

Abstract
BACKGROUND: Poncirin (PO) and isosakuranetin (or ponciretin [PT]) are compounds found in fruits of the genus Citrus. They are frequently used in traditional Chinese medicine for the treatment of inflammation and asthma. Therefore, we examined their anti-gastritis effects in vitro and in vivo.
METHODS: The anti-inflammatory effects of PO and PT were examined using ethanol- or LPS-stimulated KATO III cells. Gastritis was induced in ICR mice via intragastric injection of absolute ethanol. Levels of inflammatory markers were measured by enzyme-linked immunosorbent assay, immunoblotting, and quantitative polymerase chain reaction.
RESULTS: Treatment with PT or PO inhibited the secretion of interleukin (IL)-8 and tumor necrosis factor (TNF) in ethanol- or LPS-stimulated KATO III cells. They also reduced the activation of nuclear factor kappa B (NF-?B). Pre-treatment with PT or PO significantly protected against ethanol-induced hemorrhagic gastritis, characterized by edema, tissue erosions, and mucosal friability in mice. Treatment with PT or PO suppressed ethanol-induced NF-?B activation and the release of TNF, IL-8, and IFN-?. The protective effect of PT was greater than that of PO and comparable to ranitidine, a positive control.
CONCLUSION: PT may attenuate ethanol-induced gastritis by inhibiting the infiltration of immune cells, including neutrophils, via the regulation of CXCL4 (or IL-8) secretion and the activation NF-?B.

PMID: 28013186 [PubMed – as supplied by publisher]

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[Lipid derivative of benzylidene malononitrile AG490 attenuates airway inflammation of mice with neutrophilic asthma].

[Lipid derivative of benzylidene malononitrile AG490 attenuates airway inflammation of mice with neutrophilic asthma].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2016 Jun;32(6):730-733

Authors: Zhang M, Nong G, Jiang M, Zhan W

Abstract
Objective To observe the effect of lipid derivative of benzylidene malononitrile AG490 on the airway inflammation in a mouse model of neutrophilic asthma (NA). Methods Fifty-four specific pathogen-free (SPF) female C57BL/6 mice were randomly divided into 3 groups: NA group, AG490-treated NA (NAAG) group, and normal control (NC) group, 18 mice in each group. The NA group and the NAAG group were sensitized by airway instillation of ovalbumin (OVA) and lipopolysaccharide (LPS) on day 0, 6 and 13. The NAAG group was injected with AG490 (500 ?g/mouse, i.p.) three times a week, from day 0 after the first sensitization, for 3 weeks. Mice were challenged on day 21, 22 for 1 hour/time with an aerosol of 10 g/L OVA. At 24 hours after the final challenge, bronchoalveolar lavage fluid (BALF) was collected. The total number and differential counts of nucleated cells and the percentage of each type were determined. HE staining and PAS staining was employed for observing the lung pathological changes. The percentages of Th17 cells and regulatory T cells (Treg) in the lung issue were determined by flow cytometry. The level of interleukin-17 (IL-17) in BALF was measured using ELISA. Results Compared with the NA group, the total number of nucleated cells, the percentage of neutrophils and the percentage of eosinophils in BALF in the NAAG group were obviously reduced; lung tissue pathologic changes were improved in the NAAG group; goblet cell hyperplasia and the level of IL-17 in BALF in the NAAG group were significantly down-regulated; the proportion of Treg in the lung increased and the proportion of Th17 cells in the lung decreased in the NAAG group. Conclusion After NA mice are treated with AG490 during the sensitization phase, the proportion of Treg in the lung would increase and the proportion of Th17 cells in the lung would decrease. AG490 could attenuate the airway inflammation in the mouse model of NA.

PMID: 27371836 [PubMed – as supplied by publisher]

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Abietic acid attenuates allergic airway inflammation in a mouse allergic asthma model.

Abietic acid attenuates allergic airway inflammation in a mouse allergic asthma model.

Int Immunopharmacol. 2016 Jun 16;38:261-266

Authors: Gao Y, Zhaoyu L, Xiangming F, Chunyi L, Jiayu P, Lu S, Jitao C, Liangcai C, Jifang L

Abstract
Abietic acid (AA), one of the terpenoids isolated from Pimenta racemosa var. grissea, has been reported to have anti-inflammatory and immunomodulatory effects. However, the anti-allergic effects of AA remain unclear. The aim of this study was to investigate the anti-allergic effects of AA in an ovalbumin (OVA)-induced asthma murine model. The model of mouse asthma was established by induction of OVA. AA (10, 20, 40mg/kg) was administered by oral gavage 1h after the OVA treatment on days 21 to 23. At 24h after the last challenge, bronchoalveolar lavage fluid (BALF) and lung tissues were collected to assess pathological changes, cytokines production, and NF-?B expression. The results showed that AA attenuated lung histopathologic changes, inflammatory cells infiltration, and bronchial hyper-responsiveness. AA also inhibited OVA-induced the nitric oxide (NO), IL-4, IL-5, IL-13, and OVA-specific IgE production, as well as NF-?B activation. In conclusion, the current study demonstrated that AA exhibited protective effects against OVA-induced allergic asthma in mice and the possible mechanism was involved in inhibiting NF-?B activation.

PMID: 27318791 [PubMed – as supplied by publisher]

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STAT1 Attenuates Murine Allergen-Induced Airway Remodeling and Exacerbation by Carbon Nanotubes.

STAT1 Attenuates Murine Allergen-Induced Airway Remodeling and Exacerbation by Carbon Nanotubes.

Am J Respir Cell Mol Biol. 2015 Mar 25;

Authors: Thompson EA, Sayers BC, Glista-Baker EE, Shipkowski KA, Ihrie MD, Duke KS, Taylor AJ, Bonner JC

Abstract
Asthma is characterized by a T-helper 2 (Th2) phenotype and by chronic allergen-induced airway inflammation (AAI). Environmental exposure to air pollution ultrafine particles (i.e., nanoparticles) exacerbates AAI and a concern is possible exacerbation posed by engineered nanoparticles generated by emerging nanotechnologies. STAT1 is a transcription factor that maintains Th1 cell development. However, the role of STAT1 in regulating AAI or exacerbation by nanoparticles has not been explored. In this study, mice with whole body knock-out of the Stat1 gene (Stat1-/-) or wild type (WT) mice were sensitized to ovalbumin (OVA) allergen and then exposed to multi-walled carbon nanotubes (MWCNTs) by oropharygneal aspiration. In Stat1-/- and WT mice, OVA increased eosinophils in bronchoalveolar lavage fluid (BALF), while MWCNTs increased neutrophils. Interestingly, OVA sensitization prevented MWCNT-induced neutrophilia and caused only eosinophilic inflammation. Stat1-/- mice displayed increased IL-13 in BALF 1 day compared to WT mice after treatment with OVA or OVA and MWCNT. At 21 days the lungs of OVA-sensitized Stat1-/- mice displayed increased eosinophilia, goblet cell hyperplasia, airway fibrosis, and subepithelial apoptosis. MWCNTs further increased OVA-induced goblet cell hyperplasia, airway fibrosis, and apoptosis in Stat1-/- mice at 21 days. These changes corresponded to increased levels of pro-fibrogenic mediators (TGF-?1, TNF-?, OPN) but decreased IL-10 in Stat1-/- mice. Finally, fibroblasts isolated from the lungs of Stat1-/- mice produced significantly more collagen mRNA and protein in response to TGF-?1 compared to WT lung fibroblasts. Our results support a protective role for STAT1 in chronic AAI and exacerbation of remodeling caused by MWCNTs.

PMID: 25807359 [PubMed – as supplied by publisher]

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SOCS3 Silencing Attenuates Eosinophil Functions in Asthma Patients.

SOCS3 Silencing Attenuates Eosinophil Functions in Asthma Patients.

Int J Mol Sci. 2015;16(3):5434-5451

Authors: Zafra MP, Cañas JA, Mazzeo C, Gámez C, Sanz V, Fernández-Nieto M, Quirce S, Barranco P, Ruiz-Hornillos J, Sastre J, Del Pozo V

Abstract
Eosinophils are one of the key inflammatory cells in asthma. Eosinophils can exert a wide variety of actions through expression and secretion of multiple molecules. Previously, we have demonstrated that eosinophils purified from peripheral blood from asthma patients express high levels of suppressor of cytokine signaling 3 (SOCS3). In this article, SOCS3 gene silencing in eosinophils from asthmatics has been carried out to achieve a better understanding of the suppressor function in eosinophils. SOCS3 siRNA treatment drastically reduced SOCS3 expression in eosinophils, leading to an inhibition of the regulatory transcription factors GATA-3 and FoxP3, also interleukin (IL)-10; in turn, an increased STAT3 phosphorilation was observed. Moreover, SOCS3 abrogation in eosinophils produced impaired migration, adhesion and degranulation. Therefore, SOCS3 might be regarded as an important regulator implicated in eosinophil mobilization from the bone marrow to the lungs during the asthmatic process.

PMID: 25764157 [PubMed – as supplied by publisher]

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Paeoniflorin attenuates allergic inflammation in asthmatic mice.

Paeoniflorin attenuates allergic inflammation in asthmatic mice.

Int Immunopharmacol. 2014 Nov 26;

Authors: Sun J, Wu J, Xu C, Luo Q, Li B, Dong J

Abstract
Paeoniflorin (PF), one of the major active ingredients of Chinese peony, has demonstrated anti-inflammatory and immunoregulatory effects. However, it has remained unclear whether PF treatment can inhibit allergic inflammation in asthma. In this study, we evaluated the effects of PF on pulmonary function and airway inflammation in asthmatic mice. The allergic asthma models were established in BALB/c mice. The mice were sensitized and challenged with ovalbumin. Airway hyperresponsiveness was detected by direct airway resistance analysis. Lung tissues were examined for inflammatory cell infiltration. IL-5, IL-13, IL-17, and eotaxin in bronchoalveolar lavage fluid (BALF) and their mRNA expression in lung tissue were examined by ELISA and realtime PCR, respectively. The total IgE level in serum was measured by ELISA. The protein expression of p-ERK and p-JNK was detected by western blot. Our data showed that PF oral administration significantly reduced airway hyperresponsiveness to aerosolized methacholine and decreased IL-5, IL-13, IL-17 and eotaxin levels in the BALF, and decreased IgE level in the serum. Histological studies showed that PF administration markedly decreased inflammatory infiltration. Similarly, treatment with PF significantly inhibited IL-5, IL-13, IL-17 and eotaxin mRNA expression in lung tissues. The protein expression levels of p-ERK and p-JNK were substantially decreased after oral administration of PF. In summary, PF displayed anti-inflammatory effects in the OVA-induced asthmatic model by decreasing the expression of IL-5, IL-13, IL-17 and eotaxin. These effects were mediated at least partially by inhibiting the activation of MAPK pathway.

PMID: 25433342 [PubMed – as supplied by publisher]

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Vitamin D improves corticosteroid efficacy and attenuates its side-effects in an animal model of asthma.

Vitamin D improves corticosteroid efficacy and attenuates its side-effects in an animal model of asthma.

Can J Physiol Pharmacol. 2014 Nov 3;:1-9

Authors: Mehta AA, Agrawal AD, Appanna V, Chaudagar KK

Abstract
The subacute use of corticosteroids has side-effects such as glucose intolerance, dyslipidemia, anxiety, and depression, which could be halted with vitamin D, which is an immunomodulatory vitamin. Thus, we aimed to study the anti-asthmatic efficacy and side-effects profile of vitamin D, the corticosteroid dexamethasone, and their combination on ovalbumin-induced airway inflammation in rats. For this, 2 different doses of vitamin D (50 IU/kg, daily for 2 weeks, or and 60000 IU/kg, bolus dose, by intraperitoneal injection (i.p.)) were administered in combination with dexamethasone (2.5 mg/kg, i.p., for 2 weeks) prior to challenge with ovalbumin. At the end of the therapy, the asthmatic parameters such as differential white blood cell counts, serum levels of immunoglobulin E, bronchoalveolar lavaged fluid, and interleukin-5, as well as serum levels of nitric oxide were significantly increased after allergen challenges in asthmatic rats as compared with the controls. Such increases were significantly attenuated by monotherapy with vitamin D and with combination therapy of vitamin D and dexamethasone, where the combination therapy was superior to the monotherapy. Dexamethasone-induced hyperglycemia, hyperlipidemia, and behavioral abnormalities in the allergic rats were attenuated with vitamin D. The daily dose was better for controlling serum levels of immunoglobulin E than the bolus dose, whereas the bolus was superior for reducing dexamethasone-induced psychotropic abnormalities. There were no significant changes in other parameters between the daily and the bolus dose. In conclusion, a daily dose of vitamin D in combination with dexamethasone is more efficacious for treating asthma in allergic rats than monotherapy.

PMID: 25429688 [PubMed – as supplied by publisher]

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Grape Seed Proanthocyanidin Extract Attenuates Airway Inflammation and Hyperresponsiveness in a Murine Model of Asthma by Downregulating Inducible Nitric Oxide Synthase.

Grape Seed Proanthocyanidin Extract Attenuates Airway Inflammation and Hyperresponsiveness in a Murine Model of Asthma by Downregulating Inducible Nitric Oxide Synthase.

Planta Med. 2011 Mar 30;

Authors: Zhou DY, Du Q, Li RR, Huang M, Zhang Q, Wei GZ

Allergic asthma is characterized by hyperresponsiveness and inflammation of the airway with increased expression of inducible nitric oxide synthase (iNOS) and overproduction of nitric oxide (NO). Grape seed proanthocyanidin extract (GSPE) has been proved to have antioxidant, antitumor, anti-inflammatory, and other pharmacological effects. The purpose of this study was to examine the role of GSPE on airway inflammation and hyperresponsiveness in a mouse model of allergic asthma. BALB/c mice, sensitized and challenged with ovalbumin (OVA), were intraperitoneally injected with GSPE. Administration of GSPE remarkably suppressed airway resistance and reduced the total inflammatory cell and eosinophil counts in BALF. Treatment with GSPE significantly enhanced the interferon (IFN)- ? level and decreased interleukin (IL)-4 and IL-13 levels in BALF and total IgE levels in serum. GSPE also attenuated allergen-induced lung eosinophilic inflammation and mucus-producing goblet cells in the airway. The elevated iNOS expression observed in the OVA mice was significantly inhibited by GSPE. In conclusion, GSPE decreases the progression of airway inflammation and hyperresponsiveness by downregulating the iNOS expression, promising to have a potential in the treatment of allergic asthma.

PMID: 21452107 [PubMed – as supplied by publisher]

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