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      Bioactivity-Guided Fractionation and NMR-Based Identification of the Immunomodulatory Isoflavone from the Roots of Uraria crinita (L.) Desv. ex DC

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          Abstract

          Uraria crinita is used as a functional food ingredient. Little is known about the association between its immunomodulatory activity and its metabolites. We applied a precise strategy for screening metabolites using immunomodulatory fractions from a U. crinata root methanolic extract (UCME) in combination with bioactivity-guided fractionation and NMR-based identification. The fractions from UCME were evaluated in terms of their inhibitory activity against the production of pro-inflammatory cytokines (IL-6 and TNF- α) by lipopolysaccharide (LPS)-stimulated mouse bone marrow-derived dendritic cells (BMDC). The role of the isoflavone genistein was indicated by the 1H NMR profiling of immunomodulatory subfractions (D-4 and D-5) and supported by the result that genistein-knockout subfractions (D-4 w/ o and D-5 w/ o) had a lower inhibitory activity compared to genistein-containing subfractions. This study suggests that genistein contributes to the immunomodulatory activity of UCME and will help in the standardization of functional food.

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          Most cited references29

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          Dendritic cells and cytokines in human inflammatory and autoimmune diseases.

          Dendritic cells (DCs) produce cytokines and are susceptible to cytokine-mediated activation. Thus, interaction of resting immature DCs with TLR ligands, for example nucleic acids, or with microbes leads to a cascade of pro-inflammatory cytokines and skewing of T cell responses. Conversely, several cytokines are able to trigger DC activation (maturation) via autocrine, for example TNF and plasmacytoid DCs, and paracrine, for example type I IFN and myeloid DCs, pathways. By controlling DC activation, cytokines regulate immune homeostasis and the balance between tolerance and immunity. The increased production and/or bioavailability of cytokines and associated alterations in DC homeostasis have been implicated in various human inflammatory and autoimmune diseases. Targeting these cytokines with biological agents as already is the case with TNF and IL-1 represents a success of immunology and the coming years will expand the range of cytokines as therapeutic targets in autoinflammatory and autoimmune pathology.
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            Pd(II)-catalyzed hydroxylation of arenes with 1 atm of O(2) or air.

            Pd(II)-catalyzed ortho-hydroxylation of variously substituted benzoic acids under 1 atm of O(2) or air is achieved under nonacidic conditions. Extensive labeling studies support a direct oxygenation of aryl C-H bonds with molecular oxygen.
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              Kaempferol from Semen cuscutae attenuates the immune function of dendritic cells.

              Dendritic cells (DCs) are the critical leukocytes in regulating immune responses. Accordingly, DCs are the major target in the development of immunomodulators. In this study, we examined the effect of Semen cuscutae (SC), an important traditional Chinese medicine, on mouse bone marrow-derived DCs. We found that the n-butanol and methanol extracts of SC significantly suppressed LPS-stimulated DC activation. Several flavonoids were verified in the extracts using HPLC, and then kaempferol was identified as the major flavonoid in the methanol fraction of SC. Kaempferol was able to reduce cytokines and chemokines produced by LPS-stimulated DCs, and this reduction was not due to its cytotoxicity on DCs. In addition, DC maturation was impaired by kaempferol. Furthermore, kaempferol abrogated the ability of LPS-stimulated DCs to promote Ag-specific T cell activation, both in vitro and in vivo. Thus, we show for the first time that SC exhibits an immunosuppressive effect on DCs and that the active ingredient kaempferol attenuates DC function, which suggests that kaempferol has potential in the treatment of chronic inflammatory and autoimmune diseases. Copyright © 2011 Elsevier GmbH. All rights reserved.
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                Author and article information

                Journal
                Foods
                Foods
                foods
                Foods
                MDPI
                2304-8158
                03 November 2019
                November 2019
                : 8
                : 11
                : 543
                Affiliations
                [1 ]Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica, Taichung 404, Taiwan; pingchen.tu@ 123456gmail.com
                [2 ]Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 404, Taiwan; ruby24301@ 123456gmail.com (C.-J.C.); kuoyh@ 123456mail.cmu.edu.tw (Y.-H.K.)
                [3 ]Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung-Hsing University, Taichung 402, Taiwan; sealioler@ 123456gmail.com
                [4 ]Department of Biotechnology, Asia University, Taichung 413, Taiwan
                [5 ]Chinese Medicine Research Center, China Medical University, Taichung 404, Taiwan
                Author notes
                [* ]Correspondence: linmk@ 123456mail.cmu.edu.tw (M.-K.L.); leemengshiou@ 123456mail.cmu.edu.tw (M.-S.L.); Tel.: +886-4-2205-3366 (M.-K.L.); +886-4-2205-3366 (M.-S.L.)
                Author information
                https://orcid.org/0000-0002-8387-4082
                https://orcid.org/0000-0001-5935-6755
                https://orcid.org/0000-0001-9075-0793
                Article
                foods-08-00543
                10.3390/foods8110543
                6915426
                31684126
                10b860ff-ee03-48eb-9afd-d958ac873706
                © 2019 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
                : 07 August 2019
                : 10 October 2019
                Categories
                Article

                uraria crinita,isoflavone,genistein,nmr-based identification,dendritic cells

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