Suppression of NF-κB pathway by crocetin contributes to attenuation of lipopolysaccharide-induced acute lung injury in mice
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.
- SourceAvailable from: Dariush Haghmorad
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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. "
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 · 0.98 Impact Factor
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ABSTRACT: Increasing evidence indicates that neuroinflammation plays an important role in neurotoxins-induced neurodegenerations. Microglia are a type of glial cells in the brain and play as the first and main form of active immune defense in the central nervous system. Accumulated data suggest that the activation of microglia plays a critical role in neurotoxicities induced by environmental toxicants. So the inhibition of microglia has been proven to be an effective strategy against neurotoxic effects. In the present study, we found that n-3 polyunsaturated fatty acids can inhibit both microglial activation and dopaminergic injury in the substantia nigra of Sprague-Dawley rats induced by lipopolysaccharide, one of the major constituents of the outer membrane of Gram-negative bacteria. Moreover, n-3 polyunsaturated fatty acids inhibited lipopolysaccharide-induced activation of nuclear factor-κB, an important transcription factor involved in microglial activation. Taken together, our results provided the first in vivo evidence that n-3 polyunsaturated fatty acids can inhibit the damage of dopaminergic neurons induced by lipopolysaccharide through their inhibitory effects on nuclear factor-κB-dependent microglial activation.NeuroToxicology 03/2012; 33(4):780-8. DOI:10.1016/j.neuro.2012.02.018 · 3.05 Impact Factor
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ABSTRACT: Recent studies show that mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) signaling pathways are two pivotal roles contributing to the development of lipopolysaccharide (LPS)-induced acute lung injury (ALI). The present study aimed to investigate the protective effect of kaempferol (Kae), a naturally occurring flavonoid compound, on ALI and explore its possible mechanisms. Male BALB/c mice with ALI, induced by intranasal instillation of LPS, were treated or not with Kae (100 mg/kg, intragastrically) 1h prior to LPS exposure. Kae treatment attenuated pulmonary edema of mice with ALI after LPS challenge, as it markedly decreased the lung W/D ratio of lung samples, protein concentration and the amounts of inflammatory cells in BALF. Similarly, LPS mediated overproduction of proinflammatory cytokines in BALF, including TNF-α, IL-1β and IL-6, was strongly reduced by Kae. Histological studies demonstrated that Kae substantially inhibited LPS-induced alveolar wall thickness, alveolar hemorrhage and leukocytes infiltration in lung tissue with evidence of reduced myeloperoxidase (MPO) activity. Kae also efficiently increased superoxide dismutase (SOD) activity of lung sample when compared with LPS group, which was obviously reduced by LPS administration. In addition, Western blot analysis indicated that the activation of MAPKs and NF-κB signaling pathways stimulated by LPS was significantly blocked by Kae. Taken together, our results suggest that Kae exhibits a protective effect on LPS-induced ALI via suppression of MAPKs and NF-κB signaling pathways, which may involve the inhibition of tissue oxidative injury and pulmonary inflammatory process.International immunopharmacology 07/2012; 14(2):209-16. DOI:10.1016/j.intimp.2012.07.007 · 2.71 Impact Factor