DA-9201 shows anti-asthmatic effects by suppressing NF-кB expression in an ovalbumin-lnduced mouse model of asthma

Abstract

Nuclear factor kappa B (NF-kappaB) regulates the expression of multiple cytokines, chemokines, and cell adhesion molecules that are involved in the pathogenesis of asthma. We investigated the anti-asthmatic effects and the mechanism of action of DA-9201, an extract of the black rice, in a mouse model of asthma. Mice immunized with ovalbumin (OVA) were administered with DA-9201 (30, 100 or 300 mg/kg) or dexamethasone (DEXA, 3 mg/kg) for 2 weeks and challenged with aerosolized OVA during the last 3 days. Anti-asthmatic effects were assessed by means of enhanced pauses, level of total IgE and Th2 cytokines in plasma or bronchoalveolar lavage fluid (BALF), the percentage of eosinophils in BALF, and histopathological examination. The expression of NF-kappaB in nuclear and cytoplasmic fraction and its DNA-binding activity in lung tissues were analyzed by means of Western blotting and electrophoretic gel mobility shift assay (EMSA), respectively. DA-9201 significantly reduced airway hyperresponsiveness (AHR), total IgE level in plasma and BALF, IL-4, IL-5, and IL-13 levels in BALF, and the percentage of eosinophils in BALF. Tissue inflammation was significantly improved by DA-9201 treatment. In addition, DA-9201 dramatically suppressed the expression of NF-kappaB and its DNA-binding activity. These results suggest that DA-9201 may be useful for the treatment of asthma and its efficacy is related to suppression of NF-kappaB pathway.

Bronchoalveolar Lavage Fluid microRNA-146a

“…[25][26][27] Indeed, the NF-kB signaling pathway is an important regulator of lung diseases. [27][28][29][30] Thus, it can be speculated that in the early stages of silicosis, macrophages release various inflammatory cytokines through activation of the NF-kB pathway, which both promotes the transcriptional activation of additional inflammatory cytokines and increases the expression of miR-146a to regulate, through negative feedback, the expression of inflammatory factors. Altered expression levels of interleukins and tumor necrosis factora in response to inflammation have been observed in silicosis.…”

Chemopreventive action of non-steroidal anti-inflammatory drugs in 9,10-dimethylbenzanthracene induced lung carcinogenesis in BALB/C mice: Expression of COX-1, COX-2 and Nf-κB

“…Nuclear factor-kB (NF-kB), initially discovered as a transcription factor in the nucleus of the B cells that binds to the enhancer of the kappa light chain of immunoglobulin, has since been shown to be expressed ubiquitously in the cytoplasm of all types of cells (Colby et al, 1998). NF-kB activation has been associated with the initiation and progression of several human cancers (Lee et al, 2005;Sweeney et al, 2004) and considered a molecular link between chronic inflammation and cancer development (Karin and Greten, 2005;Luo et al, 2005). Several lines of evidences suggest that chronic inflammation may contribute to the process of lung carcinogenesis through activation of a number of molecular pathways, including NF-kB (Ballaz and Mulshine, 2003;Naugler and Karin, 2008;Tak and Firestein, 2001;Tang et al, 2006).…”