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      Anti-inflammatory activity of the ethanol extract of Dictamnus dasycarpus leaf in lipopolysaccharide-activated macrophages

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          Abstract

          Background

          Dictamnus dasycarpus is widely used as a traditional remedy for the treatment of eczema, rheumatism, and other inflammatory diseases in Asia. The current study investigates the molecular mechanism of anti-inflammatory action of the ethanol extract of Dictamnus dasycarpus leaf (DE) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells.

          Methods

          Nitric oxide (NO) production was assessed by Griess reaction and the mRNA and protein expressions of pro inflammatory cytokines, transcription factor, and enzymes were determined by real-time RT-PCR and immunoblotting analysis.

          Results

          DE (0.5 and 1 mg/mL) suppressed the NO production by 10 and 33%, respectively, compared to the untreated group in LPS-stimulated RAW 264.7 cells. DE (0.5 and 1 mg/mL) reduced the mRNA expression of key transcription factor nuclear factor-κB by 7 and 24%, respectively compared to the untreated group in LPS activated macrophage. The pro inflammatory cytokines such as tumor necrosis factor α and interleukin 1β were also decreased by DE treatment. Moreover, the protein expression of pro inflammatory enzymes, inducible nitric oxide synthase and cyclooxygenase 2 were also dramatically attenuated by DE in a dose dependent manner.

          Conclusions

          These results suggest that Dictamnus dasycarpus leaf has a potent anti-inflammatory activity and can be used for the development of new anti-inflammatory agents.

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          Most cited references21

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          Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids.

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            Proinflammatory cytokines.

            To review the concept of proinflammatory cytokines. Review of published literature. Academic (university hospital). Cytokines are regulators of host responses to infection, immune responses, inflammation, and trauma. Some cytokines act to make disease worse (proinflammatory), whereas others serve to reduce inflammation and promote healing (anti-inflammatory). Attention also has focused on blocking cytokines, which are harmful to the host, particularly during overwhelming infection. Interleukin (IL)-1 and tumor necrosis factor (TNF) are proinflammatory cytokines, and when they are administered to humans, they produce fever, inflammation, tissue destruction, and, in some cases, shock and death. Reducing the biological activities of IL-1 and TNF is accomplished by several different, but highly specific, strategies, which involve neutralizing antibodies, soluble receptors, receptor antagonist, and inhibitors of proteases that convert inactive precursors to active, mature molecules. Blocking IL-1 or TNF has been highly successful in patients with rheumatoid arthritis, inflammatory bowel disease, or graft-vs-host disease but distinctly has not been successful in humans with sepsis. Agents such as TNF-neutralizing antibodies, soluble TNF receptors, and IL-1 receptor antagonist have been infused into > 10,000 patients in double-blind, placebo-controlled trials. Although there has been a highly consistent small increase (2 to 3%) in 28-day survival rates with anticytokine therapy, the effect has not been statistically significant. Anticytokine therapy should be able to "rescue" the patient whose condition continues to deteriorate in the face of considerable support efforts. Unfortunately, it remains difficult to identify those patients who would benefit from anticytokine therapy for septic shock.
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              Inhibiting NF-κB activation by small molecules as a therapeutic strategy.

              Because nuclear factor-κB (NF-κB) is a ubiquitously expressed proinflammatory transcription factor that regulates the expression of over 500 genes involved in cellular transformation, survival, proliferation, invasion, angiogenesis, metastasis, and inflammation, the NF-κB signaling pathway has become a potential target for pharmacological intervention. A wide variety of agents can activate NF-κB through canonical and noncanonical pathways. Canonical pathway involves various steps including the phosphorylation, ubiquitination, and degradation of the inhibitor of NF-κB (IκBα), which leads to the nuclear translocation of the p50-p65 subunits of NF-κB followed by p65 phosphorylation, acetylation and methylation, DNA binding, and gene transcription. Thus, agents that can inhibit protein kinases, protein phosphatases, proteasomes, ubiquitination, acetylation, methylation, and DNA binding steps have been identified as NF-κB inhibitors. Because of the critical role of NF-κB in cancer and various chronic diseases, numerous inhibitors of NF-κB have been identified. In this review, however, we describe only small molecules that suppress NF-κB activation, and the mechanism by which they block this pathway. Copyright © 2010 Elsevier B.V. All rights reserved.
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                Author and article information

                Contributors
                Chiranjit.nias@gmail.com
                bora4989@naver.com
                batabyals2009@gmail.com
                tjeon73@gmail.com
                y64h@korea.kr
                sghwang@hknu.ac.kr
                Journal
                BMC Complement Altern Med
                BMC Complement Altern Med
                BMC Complementary and Alternative Medicine
                BioMed Central (London )
                1472-6882
                3 September 2014
                3 September 2014
                2014
                : 14
                : 1
                : 330
                Affiliations
                [ ]Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, 560 012 India
                [ ]Department of Animal Life and Environmental Science, Hankyong National University, Anseong, 456-749 Republic of Korea
                [ ]Department of Veterinary Biochemistry, West Bengal University of Animal and Fishery Sciences, Kolkata, India
                [ ]Department of Animal Science, College of Agriculture & Life Sciences, Chonnam National University, Gwangju, Republic of Korea
                [ ]Animal Environment Division, National Institute of Animal Science, R.D.A., Suwon, 441-706 Republic of Korea
                Article
                1901
                10.1186/1472-6882-14-330
                4161857
                25182043
                ccfa6734-048f-4dd8-b627-5f4273df6f2d
                © Ghosh et al.; licensee BioMed Central Ltd. 2014

                This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.

                History
                : 9 April 2013
                : 5 August 2014
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2014

                Complementary & Alternative medicine
                dictamnus dasycarpus,nf-κb,nitric oxide,cytokines,macrophages,inflammation

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