Article

Suppression of NF-κB pathway by crocetin contributes to attenuation of lipopolysaccharide-induced acute lung injury in mice.

Department of pharmacology, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, PR China.
European journal of pharmacology (Impact Factor: 2.59). 09/2011; 674(2-3):391-6. DOI: 10.1016/j.ejphar.2011.08.029
Source: PubMed

ABSTRACT Crocetin, a carotenoid compound, has been shown to reduce expression of inflammation and inhibit the production of reactive oxygen species. In the present study, the effect of crocetin on acute lung injury induced by lipopolysaccharide (LPS) was investigated in vivo. In the mouse model, pretreatment with crocetin at dosages of 50 and 100 mg/kg reduced the LPS-induced lung oedema and histological changes, increased LPS-impaired superoxide dismutase (SOD) activity, and decreased lung myeloperoxidase (MPO) activity. Furthermore, treatment with crocetin significantly attenuated LPS-induced mRNA and the protein expressions of interleukin-6 (IL-6), macrophage chemoattractant protein-1 (MCP-1), and tumour necrosis factor-α (TNF-α) in lung tissue. In addition, crocetin at different dosages reduced phospho-IκB expression and NF-κB activity in LPS-induced lung tissue alteration. These results indicate that crocetin can provide protection against LPS-induced acute lung injury in mice.

0 Bookmarks
 · 
106 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Since steroids and cyclooxygenase inhibitors may cause serious side effects, the IκB kinase (IKK) β/nuclear factor-κB (NF-κB) system becomes an intriguing candidate anti-inflammatory target. Rhein, the active metabolite of diacerein, possesses anti-inflammatory ability with gastrointestinal protective effect. However, in our preliminary study,we accidentally found that rhein showed both anti- and pro-inflammatory activities in lipopolysaccharide (LPS)-activated macrophages. Thus, in this study, we explored the underlying molecular mechanisms of the dual effect of rhein. In LPS-activated macrophages, rhein inhibits NF-κB activation and sequentially suppresses its downstream inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) transcriptions and supernatant nitric oxide (NO) and IL-6 levels by inhibiting IKKβ (IC50≈11.79μM). But in the meantime, rhein enhances the activity of caspase-1 through inhibiting intracellular (in situ) IKKβ, in turn increasing the IL-1β and high mobility group box 1 (HMGB1) release, which can be amplified by rhein's reductive effect on intracellular superoxide anion (O2(-)). Unexpectedly, it is because of IKKβ inhibition that rhein significantly enhances TNF-α secretion and phagocytosis in macrophages with or without LPS. These results indicate that rhein exerts anti- and pro-inflammatory activities by targeting IKKβ inhibition, providing a molecular mechanism for the unanticipated role of rhein in macrophages. Furthermore, our study also highlights the potential complications of IKKβ inhibitors (e.g. rhein and diacerein, etc.) application in inflammation disorders, for the overall effects of IKKβ inhibition in different organ systems and disease processes are not easily predictable under all circumstances.
    Free Radical Biology and Medicine 04/2014; · 5.27 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This study aims to evaluate the possible mechanisms responsible for the anti-inflammatory effects of apigenin lipopolysaccharide (LPS)-induced inflammatory in acute lung injury. In this study, the anti-inflammatory effects of apigenin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and the possible mechanisms involved in this protection were investigated. Pretreatment with apigenin prior to the administration of intratracheal LPS significantly induced a decrease in lung wet weight/dry weight ratio in total leukocyte number and neutrophil percent in the bronchoalveolar lavage fluid (BALF) and in IL-6 and IL-1β, the tumor neurosis factor-α (TNF-α) in the BALF. These results showed that anti-inflammatory effects of apigenin against the LPS-induced ALI may be due to its ability of primary inhibition of cyclooxygenase-2 (COX-2) gene expression and nuclear factor kB (NF-kB) gene expression of lung. The results presented here suggest that the protective mechanism of apigenin may be attributed partly to decreased production of proinflammatory cytokines through the inhibition of COX-2 and NF-kB activation. The results support that use of apigenin is beneficial in the treatment of ALI.
    Inflammation 06/2014; · 1.92 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background The anti-oxidative and anti-inflammatory activities of electro-acupuncture (EA), a traditional clinical method, are widely accepted, but its mechanisms are not yet well defined. In this study, we investigated the role of extracellular signal-regulated kinases1/2 (ERK1/2) pathways on electro-acupuncture - mediated up-regulation of heme oxygenase-1 (HO-1) in rabbit lungs injured by LPS-induced endotoxic shock. Material and Methods Seventy rabbits were randomly divided into 7 groups: group C, group M, group D, group SEAM, group EAM, group EAMPD, and group PD98059. Male New England white rabbits were given EA treatment on both sides once a day on days 1-5, and then received LPS to replicate the experimental model of injured lung induced by endotoxic shock. Then, they were killed by exsanguination at 6 h after LPS administration. The blood samples were collected for serum examination, and the lungs were removed for pathology examination, determination of wet-to-dry weight ratio, MDA content, SOD activity, serum tumor necrosis factor-α, determination of HO-1 protein and mRNA expression, and determination of ERK1/2 protein. Results The results revealed that after EA treatment, expression of HO-1and ERK1/2 was slightly increased compared to those in other groups, accompanied with less severe lung injury as indicated by lower index of lung injury score, lower wet-to-dry weight ratio, MDA content, and serum tumor necrosis factor-α levels, and greater SOD activity (p<0.05 for all). After pretreatment with ERK1/2 inhibitor PD98059, the effect of EA treatment and expression of HO-1 were suppressed (p<0.05 for all). Conclusions After electro-acupuncture stimulation at ST36 and BL13, severe lung injury during endotoxic shock was attenuated. The mechanism may be through up-regulation of HO-1, mediated by the signal transductions of ERK1/2 pathways. Thus, the regulation of ERK1/2 pathways via electro-acupuncture may be a therapeutic strategy for endotoxic shock.
    Medical science monitor: international medical journal of experimental and clinical research 01/2014; 20:1452-60. · 1.22 Impact Factor