Jingguo Wu

Rhein attenuates inflammation through inhibition of NF-κB and NALP3 inflammasome in vivo and in vitro

Rhein is an important component in traditional Chinese herbal medicine formulations for gastrointestinal disorders, including inflammatory bowel diseases such as ulcerative colitis. In this study, we investigated the beneficial effects of rhein in inflammation models in the transgenic zebrafish line TG (corolla eGFP), in which both macrophages and neutrophils express eGFP and RAW264.7 macrophages. We found that the tail-cutting-induced migration of immune cells was significantly reduced in transgenic zebrafish treated with rhein. In addition, the production of proinflammatory cytokines, including IL-6, IL-1β, and tumor necrosis factor-α, were significantly reduced in lipopolysaccharide (LPS)-induced RAW264.7 macrophages treated with rhein. Parallel to the inhibition of proinflammatory cytokines, rhein significantly reduced phosphorylation levels of NF-κB p65 and inducible nitric oxide synthase, as well as COX-2 protein expression levels. Furthermore, rhein significantly reduced NALP3 and cleaved IL-1β expression in LPS + ATP-induced RAW264.7 macrophages. Thus, the present study demonstrates that rhein may exhibit its anti-inflammatory action via inhibition of NF-κB and NALP3 inflammasome pathways.

Micrometam C Protects against Oxidative Stress in Inflammation Models in Zebrafish and RAW264.7 Macrophages

Micrometam C is a core of novel marine compound isolated from the mangrove associates Micromelum falcatum. In this study, we investigated the protective effects of micrometam C in inflammation models in the transgenic zebrafish line Tg (corola: eGFP) and RAW264.7 macrophages. We found that micrometam C significantly suppressed the migration of immune cells in tail-cutting-induced inflammation in transgenic zebrafish and reduced lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) in both zebrafish and macrophages. In addition, micrometam C also restored LPS-induced reduction of endogenous antioxidants, such as catalase (CAT), glutathione (GSH) and superoxide dismutase (SOD). The protective effects of micrometam C were in parallel to its inhibition of NADPH oxidase and nuclear factor-kappa-binding (NF-κB) activity. Thus, the present results demonstrate that micrometam C protects against LPS-induced inflammation possibly through its antioxidant property.

Recombinant Trichinella spiralis 53-kDa protein activates M2 macrophages and attenuates the LPS-induced damage of endotoxemia:

Sepsis is a serious clinical condition of excessive systemic immune response to microbial infection. The pro-inflammatory stage of sepsis is generally launched by innate cells such as macrophages. They release inflammatory cytokines, activate other immune cells and cause severe tissue/organ damage. In this study, we have revealed that recombinant Trichinella spiralis (TS) excretory–secretory protein (rTsP53) exhibited anti-inflammatory properties and rescued mice from LPS-induced endotoxemia, which is a common model for sepsis study, potentially through the induction of M2 macrophages. rTsP53 treatment significantly decreased inflammatory cytokines (IL-6, IFN-γ and TNF-α) and increased IL-4, IL-10, IL-13 and TGF-β secretion, both in circulation and in tissues. rTsP53 also induced the activation and infiltration of F4/80+CD163+ macrophages to inflammatory tissues, increased M2 macrophage-related Arg1 and Fizz1 expression, and decreased M1 macrophage-related iNOS expression. PCR array showed that rTsP53 activated several genes that involve the survival of macrophages and also anti-inflammatory genes such as SOCS3. Together, our results show that rTsP53 activates M2 macrophages, which has strong anti-inflammatory potential to prevent LPS-induced lethal sepsis.

Soluble Egg Antigen Activates M2 Macrophages via the STAT6 and PI3K Pathways, and Schistosoma Japonicum Alternatively Activates Macrophage Polarization to Improve the Survival Rate of Septic Mice

Sepsis is one of the most challenging health problems worldwide. Our previous study showed that chronic schistosoma japonica (SJ) infection might increase serum anti‐inflammatory factors to play a protective role, thus improving the survival rate of septic mice. Further research revealed that SJ infection promoted J774A.1 macrophage differentiation into M2 macrophages; suppressed LPS‐induced activation of M1 macrophages; up‐regulated CD163, IL‐10, and TGF‐β1 expression; inhibited TNF‐α and iNOS expression; and blocked the effect of LPS‐promoted TNF‐α and iNOS expression. Furthermore, adoptive transfer of ex vivo programed M2 macrophages significantly increased the survival rate of septic mice. In vitro studies suggested that soluble egg antigen (SEA) from SJ played the same role as worm infection but had no impact on M1 macrophages. SEA reduced LPS‐induced TNF‐α and iNOS expression, decreased the inhibitory effect of LPS on IL‐10 and TGF‐β1 expression, increased STAT6 phosphorylation, and up‐regulated PI3K and Akt expression but inhibited SOCS1 expression. When PI3K inhibitors were added, SEA‐induced expression of CD163, IL‐10, and arg1 might be reduced. Therefore, worm infection has a protective effect in septic mice in which SEA may play a key role via the STAT6 and PI3K pathways. This finding may provide a favorable solution for the treatment of sepsis, especially early cases. J. Cell. Biochem. 118: 4230–4239, 2017.

Chrysin attenuates myocardial ischemia–reperfusion injury by inhibiting myocardial inflammation

The aim of this study was to investigate the effects of chrysin (CH) on myocardial ischemia–reperfusion injury. Cytokines were reduced by CH in coronary artery occlusion-induced rats and also in H9C2 cells. The ST segment was also restored by CH. Triphenyltetrazolium chloride (TTC) staining and pathological analysis showed that CH could alleviate myocardial injury. Results in H9C2 cells showed that CH improved heart injury in hypoxia/reoxygenation (H/R) of H9C2 cells. In addition, the expressions of the HMGB1-related inflammation pathway in rats and H9C2 cells were significantly decreased by CH. The present study shows the protective effects of CH on myocardial injury via inflammation.

GW26-e0494 Effectiveness and safety of tolvaptan in chinese heart failure patients with reduced left ventricular systolic function

To examine the efficacy and safety of tolvaptan in acute decompensated heart failure patients with reduced left ventricular systolic function. A total of 145 hospitalized acute decompensated heart failure patients were randomly assigned to either a tolvaptan(n=79) or a control group(n=66) which

e0442 Effect of aspirin and cilostazol on inflammatory cytokines in patients with acute coronary syndrome

Objective To investigate the effect of aspirin and cilostazol on interleukin-6 (IL-6) and high sensitive C reactive protein (hsCRP) and platelet-activating factor acetylhydrolase (PAF-AH) in acute coronary syndrome (ACS) patients and the difference between them. Methods 72 patients with ACS were randomly divided into two groups: the aspirin group (n=34) and cilostazol group (n=38). All patients were given routine therapy including rest, oxygen inhaling, anticoagulating, reducing blood lipid levels, controlling the blood pressure. The patients in the aspirin group were given aspirin 0.1 g every day in addition. The patients in the cilostazol group were given cilostazol 0.1 g twice a day underlying the routine therapy. The course of treatment was 4 weeks. Observe the IL-6 and hsCRP and PAF-AH in serum and on peripheral blood mononuclear cells of the patients before and after treatment. Result The basic characteristics of the two groups were identical (p>0.05). The content of IL-6 and hsCRP were all significantly decreased after therapy (p<0.05), and the content of PAF-AH were significantly increased after therapy (p<0.05). The content of IL-6 (25.9±7.5 vs 20.3±9.8 pg/ml) and hsCRP (9.5±2.1 vs 6.1±1.9 g/l) in aspirin group (after treatment) were significantly higher than those in cilostazol group (after treatment)(p<0.05), and PAF-AH (27.2±5.6 vs 36.8±2.6 μmolċmin−1l−1) in aspirin group (after treatment) were significantly lower than those in cilostazol group (after treatment) (p<0.05). Conclution Aspirin and cilostazol can decrease IL-6 and hsCRP level and increase PAF-AH level in ACS patients. And cilostazol is more effective than aspirin to inhibit the inflammatory response in ACS patients.