International immunopharmacology
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Int. Immunopharmacol. · Feb 2009
Inhibitory effects of flavonoids extracted from licorice on lipopolysaccharide-induced acute pulmonary inflammation in mice.
Airway inflammation plays important roles in the pathogenesis of acute respiratory distress syndrome (ARDS), asthma and chronic obstructive pulmonary disease (COPD), and anti-inflammatory treatment effectively improves the symptoms of these diseases. To develop the potentially therapeutic compounds for the treatment of pulmonary inflammation, we investigated the effects of licorice flavonoids (LF) extracted from the roots of Glycyrrhiza uralensis (licorice) on lipopolysaccharide (LPS)-induced acute pulmonary inflammation in mice. Acute pulmonary inflammation was induced by intracheal instillation with LPS, treatment with LF at dosages of 3, 10 and 30 mg/kg significantly reduced the LPS-induced inflammatory cells, including neutrophils, macrophages and lymphocytes accumulation in bronchoalveolar lavage fluids (BALF), among these inflammatory cells, LF predominately inhibited neutrophil infiltration, and the maximal effect (30 mg/kg) was as comparable as dexamethasone treatment at 1 mg/kg. ⋯ Furthermore, treatment with LF at 30 mg/kg significantly reduced LPS-induced lung TNFalpha and IL-1beta mRNA expression at 6 h and 24 h after LPS instillation, respectively. Finally, LF at different dosages not only significantly decreased the elevation of lung water content, but also markedly attenuated LPS-induced histological alteration. Therefore, we suggest that LF effectively attenuates LPS-induced pulmonary inflammation through inhibition of inflammatory cells infiltration and inflammatory mediator release which subsequently reduces neutrophil recruitment into lung and neutrophil-mediated oxidative injury, and this study provides with the potential rationale for development of anti-inflammatory compounds from flavonoid extracts of licorice.
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Int. Immunopharmacol. · Jan 2009
Nociceptive and inflammatory responses induced by formalin in the orofacial region of rats: effect of anti-TNFalpha strategies.
This study evaluated the effects of different anti-TNFalpha strategies on the nociceptive and inflammatory responses triggered by formalin in the rat orofacial region. Formalin injection (2.5%) into the right upper lip caused a nociceptive response that was biphasic, with the first phase observed between 0 and 3 min and the second phase between 12 and 30 min. Plasma extravasation induced by formalin was time-related and reached the peak at 360 min. ⋯ The local administration of the monoclonal antibody anti-TNFalpha (25 and 50 pg/lip) or infliximab (50 pg/lip) markedly reduced the plasma extravasation induced by formalin. Otherwise, formalin-elicited plasma extravasation was not significantly affected by the systemic administration of either infliximab (1 mg/kg; s.c) or thalidomide (50 mg/kg, p.o). Present data suggest that blocking TNFalpha effects, through different pharmacological tools, could represent a good alternative to control orofacial inflammatory pain that is refractory to other drugs.
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Int. Immunopharmacol. · Dec 2008
PACAP inhibit the release and cytokine activity of HMGB1 and improve the survival during lethal endotoxemia.
The pathogenesis of sepsis is mediated in part by bacterial endotoxin (lipopolysaccharide; LPS), which stimulates macrophages/monocytes to sequentially release early (e.g., TNF-alpha, IL-1beta) and late [e.g., high mobility group box 1 (HMGB1) protein] pro-inflammatory cytokines. Specifically targeting early mediators has not been effective clinically, in part, because peak mediator activity often has passed before therapy can be initiated. Recent discovery of HMGB1 as a late mediator of lethal sepsis has provided a new target for the treatment of septic shock. ⋯ PACAP also suppressed HMGB1 release induced by TNF-alpha or IFN-gamma. Moreover, PACAP inhibits HMGB1-induced cytokine release in vitro and in vivo. These results indicate that PACAP inhibits the release and pro-inflammatory activity of HMGB1 and improves survival during lethal endotoxemia, which confirms this peptide as a candidate for therapy of septic shock.
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Int. Immunopharmacol. · Jul 2008
Ursolic acid induces apoptosis by activating p53 and caspase-3 gene expressions and suppressing NF-kappaB mediated activation of bcl-2 in B16F-10 melanoma cells.
The objective of this study was to assess the effect of ursolic acid, a triterpene on inducing apoptosis in B16F-10 melanoma cells. Treatment of B16F-10 cells with nontoxic concentration of ursolic acid showed the presence of apoptotic bodies and induced DNA fragmentation in a dose depended manner. ⋯ The pro-inflammatory cytokine production and gene expression of TNF-alpha, IL-1beta, IL-6 and GM-CSF were down regulated in ursolic acid treated cells compared to nontreated B16F-10 metastatic melanoma cells. All these results demonstrate that ursolic acid induce apoptosis via inhibition of NF-kappaB induced bcl-2 mediated anti-apoptotic pathway and subsequent activation of p53 mediated and TNF-alpha induced caspase-3 mediated pro-apoptotic pathways.
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Sepsis is a complex clinical syndrome resulting from a harmful host inflammatory response to infection. Similarly, lipopolysaccharide (LPS) induced endotoxemia is marked by the activation of inflammatory responses, which can lead to shock, multiple organ damage and even death. Inflammatory mediator, chemokines are known to play an important role in the pathogenesis of sepsis and endotoxemia. ⋯ The protective effect of bindarit was further confirmed by histological examination of lung and liver sections. Treatment with bindarit reduced lung and liver injury as indicated by decreased thickening of alveolar and neutrophil infiltration in CLP-induced sepsis and LPS-induced endotoxemia. Considering these results, we propose that anti-MCP-1 strategies may be of potential therapeutic value in the treatment of sepsis and endotoxemia.