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: 2.53). 09/2011; 674(2-3):391-6. DOI: 10.1016/j.ejphar.2011.08.029
Source: PubMed


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.

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    • "Acute respiratory distress syndrome (ARDS), an indication of acute lung injury (ALI), is highly associated with endotoxic shock [1]. ALI and ARDS, which represent the severest form of lung injury associated with endotoxic shock, are the leading causes of morbidity and mortality in patients [2]. The first-line treatments for patients with endotoxic shock, such as antibiotics, source control, and resuscitation with intravenous fluids to optimize circulation and organ perfusion, are largely limited to persistent hypo-perfusion and end-organ dysfunctions [3]. "
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    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/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 08/2014; 20:1452-60. DOI:10.12659/MSM.890736 · 1.43 Impact Factor
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    • "It has also been shown that SEE contains many potent alkaloids and saponins (Hosseinzadeh & Younesi, 2002; Table 1). Other studies have speculated that the anti-inflammatory activity of SEE might be attributed to its content of crocin (Hemshekhar et al., 2012; Nam et al., 2010), crocetin (Nam et al., 2010; Yang et al., 2012) and safranal (Boskabady, Tabatabaee, & Byrami, 2012), agents whose individual anti-inflammatory effects were documented in the cited studies. "
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    ABSTRACT: Saffron is a well-known spice produced from dried stigmas of Crocus sativus L. flowers. Apart from its wide use in food preparations, it also has a broad range of medical properties. We examined the potential anti-inflammatory effects of saffron ethanolic extract (SEE) using an animal model of arthritis. Adjuvant-induced arthritis was induced in Wistar rats by injection of Complete Freund's Adjuvant. The rats were then injected intraperitoneally every other day with 25–600 mg SEE/kg or dexamethasone (DEX, 2 mg/kg). Changes in body weight, paw oedema and arthritis indices were recorded over the subsequent 12 days of treatment. Results revealed that SEE particularly at the higher concentrations significantly reduced paw and tibiotarsal joint diameters and comparing with DEX caused no significant change in body weight. These observations suggest that SEE displays a considerable anti-inflammatory potency and could potentially be used as an anti-arthritic agent in control of inflammation in rheumatoid arthritis.
    Food and Agricultural Immunology 01/2014; 26(2). DOI:10.1080/09540105.2013.878900 · 0.99 Impact Factor
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    • "Furthermore, some cytokines, such as interleukin-6 (IL-6) and transforming growth factor β (TGF-β), are highly involved in the pathogenesis of scleroderma (22). Crocetin has been found to attenuate the expression of IL-6 in mice (23), but whether this effect can be blocked by the addition of IL-6 remains unknown. Nevertheless, little is known regarding the effect of crocetin on other crucial cytokines, such as TGF-β. "
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    ABSTRACT: To investigate the antifibrotic effects of crocetin in scleroderma fibroblasts and in sclerotic mice. Skin fibroblasts that were isolated from three systemic scleroderma (SSc) patients and three healthy subjects were treated with crocetin (0.1, 1 or 10 μM). Cell proliferation was measured with an MTT assay. Alpha-smooth muscle actin was detected via an immunohistochemical method. Alpha 1 (I) procollagen (COL1A1), alpha 1 (III) procollagen (COL3A1), matrix metalloproteinase (MMP)-1 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 mRNA levels were measured using real-time PCR. SSc mice were established by the subcutaneous injection of bleomycin. Crocetin (50 mg/kg/d) was injected intraperitoneally for 14 days. Dermal thickness and lung fibrosis were assessed with Masson's trichrome staining. Plasma ET-1 was detected with an enzyme-linked immunosorbent assay (ELISA). Skin and lung ET-1 and COL1A1 mRNA levels were measured via real-time PCR. Crocetin inhibited the proliferation of SSc and normal fibroblasts, an effect that increased with crocetin concentration and incubation time. Crocetin decreased the expression of α-SMA and the levels of mRNA for COL1A1, COL3A1 and matrix metalloproteinase-1, while crocetin increased TIMP-1 mRNA levels in both SSc and normal fibroblasts. Skin and lung fibrosis was induced, and the levels of ET-1 in the plasma, skin and lungs were elevated in bleomycin-injected mice. Crocetin alleviated the thickening of the dermis and lung fibrosis; decreased COL1A1 mRNA levels in the skin and lung; and simultaneously decreased ET-1 concentrations in the plasma and ET-1 mRNA levels in the skin and lungs of the bleomycin-induced sclerotic mice, especially during the early phase (weeks 1-3). Crocetin inhibits cell proliferation, differentiation and collagen production in SSc fibroblasts. Crocetin alleviates skin and lung fibrosis in a bleomycin-induced SSc mouse model, in part due to a reduction in ET-1.
    Clinics (São Paulo, Brazil) 10/2013; 68(10):1350-7. DOI:10.6061/clinics/2013(10)10 · 1.19 Impact Factor
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