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      Anti-inflammatory effect of quercetin and galangin in LPS-stimulated RAW264.7 macrophages and DNCB-induced atopic dermatitis animal models

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          Abstract

          Flavonols are compounds that have been shown to possess potent anti-inflammatory effects in cellular and animal models of inflammation. In the present study, the anti-inflammatory effects and mechanisms of two natural flavonols, quercetin and galangin, in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages were investigated. It was identified that quercetin and galangin markedly reduced the production of nitric oxide (NO), inducible NO synthase and interleukin-6, and the nuclear translocation of nuclear factor-κB (NF-κB). In addition, LPS-induced activation of extracellular signal-regulated kinase 1/2 (Erk1/2) and c-Jun N-terminal kinase (JNK) was suppressed by quercetin and galangin. Taken together, these data implied that NF-κB, Erk1/2 and JNK may be potential molecular targets of quercetin and galangin in an LPS-induced inflammatory response. Subsequently, the effects of oral administration of quercetin or galangin, either alone or in combination, in a 2,4-dinitrochlorobenzene-induced atopic dermatitis (AD) mouse model were investigated. As a result, measurements of ear thickness and the levels of serum immunoglobulin E, and histological analysis revealed that the two flavonols led to a decrease in inflammation, whereas, in combination, they were even more effective. These results suggested that quercetin and galangin may be promising therapeutic agents for AD. Additionally, their combination may be a novel therapeutic strategy for the prevention of AD.

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          Most cited references31

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          NF-kappaB activation by reactive oxygen species: fifteen years later.

          The transcription factor NF-kappaB plays a major role in coordinating innate and adaptative immunity, cellular proliferation, apoptosis and development. Since the discovery in 1991 that NF-kappaB may be activated by H(2)O(2), several laboratories have put a considerable effort into dissecting the molecular mechanisms underlying this activation. Whereas early studies revealed an atypical mechanism of activation, leading to IkappaBalpha Y42 phosphorylation independently of IkappaB kinase (IKK), recent findings suggest that H(2)O(2) activates NF-kappaB mainly through the classical IKK-dependent pathway. The molecular mechanisms leading to IKK activation are, however, cell-type specific and will be presented here. In this review, we also describe the effect of other ROS (HOCl and (1)O(2)) and reactive nitrogen species on NF-kappaB activation. Finally, we critically review the recent data highlighting the role of ROS in NF-kappaB activation by proinflammatory cytokines (TNF-alpha and IL-1beta) and lipopolysaccharide (LPS), two major components of innate immunity.
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            Flavonoids as anti-inflammatory agents: implications in cancer and cardiovascular disease.

            Chronic inflammation is being shown to be increasingly involved in the onset and development of several pathological disturbances such as arteriosclerosis, obesity, diabetes, neurodegenerative diseases and even cancer. Treatment for chronic inflammatory disorders has not been solved, and there is an urgent need to find new and safe anti-inflammatory compounds. Flavonoids belong to a group of natural substances occurring normally in the diet that exhibit a variety of beneficial effects on health. The anti-inflammatory properties of flavonoids have been studied recently, in order to establish and characterize their potential utility as therapeutic agents in the treatment of inflammatory diseases. Several mechanisms of action have been proposed to explain in vivo flavonoid anti-inflammatory actions, such as antioxidant activity, inhibition of eicosanoid generating enzymes or the modulation of the production of proinflammatory molecules. Recent studies have also shown that some flavonoids are modulators of proinflammatory gene expression, thus leading to the attenuation of the inflammatory response. However, much work remains to be done in order to achieve definitive conclusions about their potential usefulness. This review summarizes the known mechanisms involved in the anti-inflammatory activity of flavonoids and the implications of these effects on the protection against cancer and cardiovascular disease.
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              Immunomodulatory mast cells: negative, as well as positive, regulators of immunity.

              Mast cells can promote inflammation and other tissue changes in IgE-associated allergic disorders, as well as in certain innate and adaptive immune responses that are thought to be independent of IgE. However, mast cells can also have anti-inflammatory and immunosuppressive functions. Here, we review the evidence that mast cells can have negative, as well as positive, immunomodulatory roles in vivo, and we propose that mast cells can both enhance and later suppress certain features of an immune response.
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                Author and article information

                Journal
                Int J Mol Med
                Int. J. Mol. Med
                IJMM
                International Journal of Molecular Medicine
                D.A. Spandidos
                1107-3756
                1791-244X
                February 2018
                29 November 2017
                29 November 2017
                : 41
                : 2
                : 888-898
                Affiliations
                [1 ]Department of Companion and Laboratory Animal Science, Kongju National University, Yesan 340702
                [2 ]Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 03080
                [3 ]Gwangju Institute of Science and Technology, School of Life Sciences, Gwangju 500712
                [4 ]School of Food Science and Technology, Chung-Ang University, Ansung 456756
                [5 ]Biomedical Center for Animal Resource Development, Seoul National University College of Medicine
                [6 ]Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea
                Author notes
                Correspondence to: Professor Ji Youn Jung or Professor Byung Kwon Park, Department of Companion and Laboratory Animal Science, Kongju National University, 54 Daehak-ro, Yesan 340702, Republic of Korea, E-mail: wangza@ 123456kongju.ac.kr , E-mail: propet@ 123456kongju.ac.kr
                Article
                ijmm-41-02-0888
                10.3892/ijmm.2017.3296
                5752163
                29207037
                18bbf3c5-0e0c-4fd8-b8d9-fe69590a3b8c
                Copyright: © Lee et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 15 February 2017
                : 16 November 2017
                Categories
                Articles

                hydroxy group,flavonol,anti-inflammation,nuclear factor-κb,mitogen-activated protein kinase

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