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      The Antioxidant and Anti-Inflammatory Activities of 8-Hydroxydaidzein (8-HD) in Activated Macrophage-Like RAW264.7 Cells

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          Abstract

          8-Hydroxydaidzein (8-HD) is a daidzein metabolite isolated from soybeans. This compound has been studied for its anti-proliferation, depigmentation, and antioxidant activities. However, the anti-inflammatory activities of 8-HD are not well-understood. Through its antioxidant effects in ABTS and DPPH assays, 8-HD reduces the production of sodium nitroprusside (SNP)-induced radical oxygen species (ROS). By triggering various Toll-like receptors (TLRs), 8-HD suppresses the inflammatory mediator nitric oxide (NO) without cytotoxicity. We examined the regulatory mechanism of 8-HD in lipopolysaccharide (LPS)-induced conditions. We found that 8-HD diminishes inflammatory gene expression (e.g., inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and tumor necrosis factor (TNF)-α) by regulating the transcriptional activities of nuclear factor (NF)-κB and activator protein 1 (AP-1). To find the potential targets of 8-HD, signaling pathways were investigated by immunoblotting analyses. These analyses revealed that 8-HD inhibits the activation of TAK1 and that phosphorylated levels of downstream molecules decrease in sequence. Together, our results demonstrate the antioxidant and anti-inflammatory actions of 8-HD and suggest its potential use in cosmetics or anti-inflammatory drugs.

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          Most cited references32

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          TLR signaling.

          The Toll-like receptor (TLR) family plays an instructive role in innate immune responses against microbial pathogens, as well as the subsequent induction of adaptive immune responses. TLRs recognize specific molecular patterns found in a broad range of microbial pathogens such as bacteria and viruses, triggering inflammatory and antiviral responses and dendritic cell maturation, which result in the eradication of invading pathogens. Individual TLRs interact with different combinations of adapter proteins and activate various transcription factors such as nuclear factor (NF)-kappaB, activating protein-1 and interferon regulatory factors, driving a specific immune response. This review outlines the recent advances in our understanding of TLR-signaling pathways and their roles in immune responses. Further, we also discuss a new concept of TLR-independent mechanisms for recognition of microbial pathogens.
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            The interleukin-1 receptor/Toll-like receptor superfamily: signal generators for pro-inflammatory interleukins and microbial products.

            The interleukin-1 (IL-1) receptor/Toll-like receptor (TLR) superfamily is a recently defined and expanding group of receptors that participate in host responses to injury and infection. The superfamily is defined by the Toll/IL-1 receptor (TIR) domain, which occurs in the cytosolic region of family members, and is further subdivided into two groups based on homology to either the Type I IL-1 receptor or Drosophila Toll receptor extracellular domain. The former group includes the receptor for the important Th1 cytokine IL-18, and T1/ST2, which may have a role in Th2 cell function. The latter group includes six mammalian TLRs, including TLR2 and TLR4, that largely mediate the host response to gram-positive and gram-negative bacteria, respectively. Whether bacterial products are actual ligands for TLRs, or whether they generate ligands via as yet unidentified pattern recognition receptors, has yet to be determined. Signaling pathways activated via the TIR domain trigger the activation of downstream kinases, and transcription factors such as NF-kappaB, and involve the adaptor protein MyD88, which itself contains a TIR domain.
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              Transcriptional regulation in the immune system: all roads lead to AP-1.

              The mechanisms regulating the development and function of the immune system are diverse and complicated. The signaling pathways and target genes that become activated upon cell-surface stimulation are currently being defined, and transcription factor activator protein 1 (AP-1) is proving to be an important regulator of nuclear gene expression in leukocytes. In vitro and in vivo studies have demonstrated that AP-1 expression is induced after a diverse range of stimuli and that AP-1 contributes to the regulation of a large number of genes. In this review we will examine the role of AP-1 during leukocyte activation and differentiation in the immune system.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                21 June 2018
                July 2018
                : 19
                : 7
                : 1828
                Affiliations
                [1 ]Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Korea; im144069@ 123456gmail.com (E.K.); kjhmlkhjml@ 123456hanmail.net (J.H.K.)
                [2 ]Basic Research & Innovation Division, R&D Center, Amorepacific Corporation, Yongin 17074, Korea; kangyg82@ 123456amorepacific.com (Y.-G.K.); jaykim@ 123456amorepacific.com (Y.-J.K.); trlee@ 123456amorepacific.com (T.R.L.)
                Author notes
                [* ]Correspondence: bioneer@ 123456skku.edu (J.L.); dhkim417@ 123456amorepacific.com (D.K.); jaecho@ 123456skku.edu or jaecho67@ 123456gmail.com (J.Y.C.); Tel.: +82-31-290-7861 (J.L.); +82-31-280-5869 (D.K.); +82-31-290-7868 (J.Y.C.)
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-1908-5310
                https://orcid.org/0000-0002-5073-2619
                https://orcid.org/0000-0001-8141-9927
                Article
                ijms-19-01828
                10.3390/ijms19071828
                6073157
                29933606
                8cc7d2a1-7bc1-4258-99fd-4eb38020cfb3
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 27 May 2018
                : 19 June 2018
                Categories
                Article

                Molecular biology
                8-hydroxydaidzein,soybeans,antioxidant,anti-inflammation
                Molecular biology
                8-hydroxydaidzein, soybeans, antioxidant, anti-inflammation

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