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Purpose: Ethyl pyruvate has anti-inflammatory properties and protects organs from ischemia/reperfusion (I/R)-induced tissue injury. The aim of this study was to determine whether ethyl pyruvate decreases the inflammatory response after regional I/R injury and whether ethyl pyruvate protects against delayed regional I/R injury in an in vivo rat heart model after a 24 hours reperfusion., Materials and Methods: Rats were randomized to receive lactated Ringer's solution or ethyl pyruvate dissolved in Ringer's solution, which was given by intraperitoneal injection 1 hour prior to ischemia. Rats were subjected to 30 min of ischemia followed by reperfusion of the left coronary artery territory. After a 2 hours reperfusion, nuclear factor κB, myocardial myeloperoxidase activity, and inflammatory cytokine levels were determined. After the 24 hours reperfusion, the hemodynamic function and myocardial infarct size were evaluated., Results: At 2 hours after I/R injury, ethyl pyruvate attenuated I/R-induced nuclear factor κB translocation and reduced myeloperoxidase activity in myocardium. The plasma circulating levels of inflammatory cytokines decreased significantly in the ethyl pyruvate-treated group. At 24 hours after I/R injury, ethyl pyruvate significantly improved cardiac function and reduced infarct size after regional I/R injury., Conclusion: Ethyl pyruvate has the ability to inhibit neutrophil activation, inflammatory cytokine release, and nuclear factor κB translocation. Ethyl pyruvate is associated with a delayed myocardial protective effect after regional I/R injury in an in vivo rat heart model.

The aloe ingredients responsible for physiological effects and the concentrations required to exert their biological activities are not fully understood. This study compares the anti-inflammatory effects of aloin and aloe-emodin with other polyphenols. Our results demonstrated that aloe-emodin dose-dependently inhibited inducible nitric oxide synthase (iNOS) mRNA expression and nitric oxide (NO) production at 5-40 microM. In addition, the levels of cyclooxygenase-2 (COX-2) mRNA and prostaglandin E2 (PGE2) production were suppressed by 40 microM aloe-emodin. Aloin also suppressed the production of NO at 5-40 microM, although it did not suppress PGE2 production. The present results indicate that aloin and aloe-emodin possibly suppress the inflammatory responses by blocking iNOS and COX-2 mRNA expression. The anti-inflammatory effect of aloe-emodin was comparable to that of kaempferol and quercetin, indicating aloe-emodin as a possible key constituent responsible for the anti-inflammatory activity of aloe.

Erdosteine is widely used as a mucolytic agent and also has free radical scavenging and antioxidant activities. However, little is known about the mechanisms of the anti-inflammatory effect of erdosteine. We investigated the effect of erdosteine on the activation of the nuclear factor (NF)-kB/inhibitor of NFkB (IkB), and the mitogen-activated protein kinase (MAPK) and Akt pathways in the mouse macrophage cell line RAW 264.7. Cultured RAW 264.7 cells were pretreated with erdosteine and stimulated with lipopolysaccharide (LPS). In Western blotting, pretreatment with erdosteine inhibited the IkBα degradation induced in RAW 264.7 cells by LPS. LPS-induced IkB kinase (IKK) activity and NF-kB transcription were inhibited by pretreatment with erdosteine. Production of IL-6 and IL-1β was also inhibited by erdosteine pretreatment. However, erdosteine did not inhibit LPS-induced phosphorylation of Akt and MAPKs. These results suggest that the anti-inflammatory effect of erdosteine in mouse macrophages is mediated through inhibition of LPS-induced NF-kB activation. [ABSTRACT FROM AUTHOR]

Background: In ulcerative colitis (UC), reduction of inflammation may represent a key mechanism in UC therapy, and anti-inflammatory agents would be good candidates for preventing UC. Kaempferol, a natural flavonoid, is believed to have anti-inflammatory activities and has been shown to be potentially immune-modulatory. Aims: The aim of this study was to determine whether kaempferol alleviates the inflammatory responses of dextran sulfate sodium (DSS)-induced colitis in mice. Methods: Female C57BL/6J mice were divided into six groups: a negative control group, a DSS control group, and DSS + 0.1% or 0.3% kaempferol pre- or post-fed groups. At the end of the experimental period, clinical and biochemical markers were evaluated. Results: Plasma levels of NO and PGE were significantly decreased in both the 0.3% kaempferol pre- and post-fed groups. The plasma LTB level was profoundly decreased in all animals fed kaempferol. Colonic mucosa MPO activity was also suppressed in both the 0.3% kaempferol pre- or post-fed groups. TFF3 mRNA, a marker for goblet cell function, was up-regulated in kaempferol pre-fed animals. Conclusions: These results indicate that kaempferol is an effective anti-inflammatory agent that protects colonic mucosa from DSS-induced UC. Dietary kaempferol fed prior to colitis induction was more effective to suppress some of the colitis-associated markers. [ABSTRACT FROM AUTHOR]

Abstract: Aims: Aloe has been a very popular folk remedy for inflammation-related pathological conditions despite the lack of studies reporting its efficacy in vivo. The present study evaluated the anti-inflammatory effects of aloe components (aloin, aloesin and aloe-gel) known to be biologically active in the rat model of colitis. Main methods: Male Sprague Dawley rats were fed experimental diets for 2weeks before and during the induction of colitis. Drinking water containing 3% dextran sulfate sodium (DSS) was provided for 1week to induce colitis. At the end of the experimental period, clinical and biochemical markers were compared. Key findings: Plasma leukotriene B4 (LTB4) and tumor necrosis factor-α (TNF-α) concentrations were significantly decreased in all groups supplemented with aloe components compared to the colitis control group (p<0.05). Animals fed both a 0.1% and 0.5% aloesin supplemented diet showed colonic myeloperoxidase (MPO) activities which were decreased by 32.2% and 40.1%, respectively (p<0.05). Colonic mucosa TNF-α and interleukin-1ß (IL-1β) mRNA expressions were significantly reduced in all animals fed aloin, aloesin, or aloe-gel (p<0.05). Significance: Dietary supplementation of aloe components ameliorates intestinal inflammatory responses in a DSS-induced ulcerative colitis rat model. In particular, aloesin was the most potent inhibitor. Further studies are required for a more complete understanding of the specific mechanism of the action of these supplements. [Copyright &y& Elsevier]

Highlights • Human cord blood (hCB) can be a source of immunosuppressive MDSCs. • Administration of hCB-MDSCs attenuates cGVHD in preclinical models. • hCB-MDSCs reduce thymic damage with less donor-derived T cell expansion. • cGVHD protection by hCB-MDSCs correlate with reversal of Th 17 skewing. • hCB-MDSCs modulate helper T cell subset and expand FoxP3 Treg. Abstract Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells with anti-inflammatory activity, and expanded murine MDSCs are capable of attenuating preclinical acute graft-versus-host disease (aGVHD) severity. Two murine cGVHD models were used to evaluate the effectiveness of ex vivo cultured human cord blood (hCB) MDSCs in chronic GVHD (cGVHD). First, GVHD recipients surviving in a classic C57BL/6 into MHC-mismatched BALB/c aGVHD model developed cGVHD. Second, donor pretreatment with granulocyte colony-stimulating factor (G-CSF) induced cGVHD. hCB-MDSCs (1 × 106) were intravenously injected to determine their preventive effects (on days 5, 7, 10, and 21) or therapeutic effects (on days 21, 28, and 35). In the first model the onset of clinical cutaneous cGVHD was significantly delayed in preventive hCB-MDSCs–treated allogeneic recipients. Pathologic scoring of target organs confirmed these clinical results. Importantly, thymic tissues of GVHD mice treated with hCB-MDSCs were less severely damaged, showing higher numbers of double (CD4 and CD8) positive T cells with reduced expansion of donor-type CD4 and CD8 T cells. Moreover, late infusion of hCB-MDSCs controlled the severity of established cGVHD that had occurred in control recipients. In the second model, cGVHD induced by G-CSF–mobilized stem cell graft was associated with promotion of Th 17 and Th 2 differentiation. hCB-MDSCs attenuated clinical and pathologic cGVHD severity. Increased production of IL-17 and more infiltration of T cells and macrophages in cGVHD mice were markedly reduced after hCB-MDSCs treatment. Importantly, Foxp3+ regulatory T cells and IFN-γ–producing T cells were expanded, whereas IL-17– and IL-4–producing T cells were decreased in allogeneic recipients of hCB-MDSCs. Taken together, these results showed that hCB-MDSCs have preclinical capability of attenuating cGVHD by preserving thymus function and regulating Th 17 signaling, suggesting a possible therapeutic strategy for clinical application. [ABSTRACT FROM AUTHOR]