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      Preparation of Herbal Formulation for Inflammatory Bowel Disease Based on In Vitro Screening and In Vivo Evaluation in a Mouse Model of Experimental Colitis

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          Abstract

          Many medicinal plants have been used traditionally in East Asia for the treatment of gastrointestinal disease and inflammation. The aim of this study was to evaluate the anti-inflammatory activity of 350 extracts (175 water extracts and 175 ethanol extracts) from 71 single plants, 97 mixtures of two plants, and seven formulations based on traditional medicine, to find herbal formulations to treat inflammatory bowel disease (IBD). In the in vitro screening, nitric oxide (NO), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 levels were determined in LPS-treated RAW264.7 cells and the TNF-α induced monocyte-epithelial cell adhesion assay was used for the evaluation of the anti-inflammatory activity of the compounds. Dextran sulfate sodium (DSS)-induced colitis model and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model were used to evaluate the therapeutic effect against IBD of the samples selected from the in vitro screening. KM1608, composed of Zingiber officinale, Terminalia chebula and Aucklandia lappa, was prepared based on the screening experiments. The oral administration of KM1608 significantly attenuated the severity of colitis symptoms, such as weight loss, diarrhea, and rectal bleeding, in TNBS-induced colitis. In addition, inflammatory mediators, such as myeloperoxidase, TNF-α, and IL-6 levels decreased in the lysate of colon tissues treated with KM1608. Collectively, KM1608 ameliorated colitis through the regulation of inflammatory responses within the colon, which indicated that KM1608 had potential for the treatment of IBD.

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          Most cited references 19

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          Function of the intestinal epithelium and its dysregulation in inflammatory bowel disease.

          The intestinal epithelium not only acts as a physical barrier to commensal bacteria and foreign antigens but is also actively involved in antigen processing and immune cell regulation. The inflammatory bowel diseases (IBDs) are characterized by inflammation at this mucosal surface with well-recognized defects in barrier and secretory function. In addition to this, defects in intraepithelial lymphocytes, chemokine receptors, and pattern recognition receptors promote an abnormal immune response, with increased differentiation of proinflammatory cells and a dysregulated relationship with professional antigen-presenting cells. This review focuses on recent developments in the structure of the epithelium, including a detailed account of the apical junctional complex in addition to the role of the enterocyte in antigen recognition, uptake, processing, and presentation. Recently described cytokines such as interleukin-22 and interleukin-31 are highlighted as is the dysregulation of chemokines and secretory IgA in IBD. Finally, the effect of the intestinal epithelial cell on T effector cell proliferation and differentiation are examined in the context of IBD with particular focus on T regulatory cells and the two-way interaction between the intestinal epithelial cell and certain immune cell populations. Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.
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            In vitro antioxidative and anti-inflammatory effects of the compound K-rich fraction BIOGF1K, prepared from Panax ginseng

            Background BIOGF1K, a compound K-rich fraction prepared from the root of Panax ginseng, is widely used for cosmetic purposes in Korea. We investigated the functional mechanisms of the anti-inflammatory and antioxidative activities of BIOGF1K by discovering target enzymes through various molecular studies. Methods We explored the inhibitory mechanisms of BIOGF1K using lipopolysaccharide-mediated inflammatory responses, reporter gene assays involving overexpression of toll-like receptor adaptor molecules, and immunoblotting analysis. We used the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay to measure the antioxidative activity. We cotransfected adaptor molecules, including the myeloid differentiation primary response gene 88 (MyD88) and Toll/interleukin-receptor domain containing adaptor molecule-inducing interferon-β (TRIF), to measure the activation of nuclear factor (NF)-κB and interferon regulatory factor 3 (IRF3). Results BIOGF1K suppressed lipopolysaccharide-triggered NO release in macrophages as well as DPPH-induced electron-donating activity. It also blocked lipopolysaccharide-induced mRNA levels of interferon-β and inducible nitric oxide synthase. Moreover, BIOGF1K diminished the translocation and activation of IRF3 and NF-κB (p50 and p65). This extract inhibited the upregulation of NF-κB-linked luciferase activity provoked by phorbal-12-myristate-13 acetate as well as MyD88, TRIF, and inhibitor of κB (IκBα) kinase (IKKβ), and IRF3-mediated luciferase activity induced by TRIF and TANK-binding kinase 1 (TBK1). Finally, BIOGF1K downregulated the NF-κB pathway by blocking IKKβ and the IRF3 pathway by inhibiting TBK1, according to reporter gene assays, immunoblotting analysis, and an AKT/IKKβ/TBK1 overexpression strategy. Conclusion Overall, our data suggest that the suppression of IKKβ and TBK1, which mediate transcriptional regulation of NF-κB and IRF3, respectively, may contribute to the broad-spectrum inhibitory activity of BIOGF1K.
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              Why patients with inflammatory bowel disease use or do not use complementary and alternative medicine: a Canadian national survey.

              The use of complementary and alternative medicine (CAM) is common in patients with inflammatory bowel disease (IBD). To determine the factors associated with use of CAM, the reasons commonly cited for use or nonuse of CAM, and the correlations between the factors associated with use of CAM and reasons for CAM use. The study included 2828 members of the Crohn's and Colitis Foundation of Canada. Subjects were mailed a questionnaire that included items on demographic characteristics, disease and treatment history, health attitudes and behaviours, and reasons for use or nonuse of CAM. Logistical regression was used to determine significant associations with current CAM use. In patients with Crohn's disease and ulcerative colitis, CAM use was associated with more severe disease activity, use of CAM for other purposes, use of exercise and prayer for IBD, and a desire for an active role in treatment decisions. CAM use was also associated with younger age in those with Crohn's disease, and less confidence in their IBD physician in those with ulcerative colitis. The most common reasons for CAM use were a desire for greater control, having heard or read that CAM might help, and the emphasis CAM places on treating the whole person. The most common reasons for not using CAM were that conventional treatments were successful, that not enough was known about CAM and a belief that CAM would not help. Disease activity and health attitudes and behaviours, but not demographic characteristics, are associated with CAM use by those with IBD.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                28 January 2019
                February 2019
                : 24
                : 3
                Affiliations
                [1 ]College of Korean Medicine, Gachon University, Seongnam-si, Gyeonggi-do 13120, Korea; jaemin.lee426@ 123456gmail.com (J.L.); jklee9441@ 123456hanmail.net (J.L.); ms.shin@ 123456gachon.ac.kr (M.-S.S.); seoul@ 123456gachon.ac.kr (G.S.H.)
                [2 ]New Drug Research Team, Kolmar, Korea Co. Ltd., Sandan-gil, Jeonui-myeon, Sejong-si 30003, Korea; fcosmos@ 123456kolmar.co.kr (H.-S.C.); jimpark@ 123456kolmar.co.kr (J.P.); m302@ 123456kolmar.co.kr (S.-B.K.)
                [3 ]College of Bio-Nanotechnology, Gachon University, Seongnam-si, Gyeonggi-do 13120, Korea; sullimlee@ 123456gachon.ac.kr
                Author notes
                [* ]Correspondence: bakoo9@ 123456kolmar.co.kr (B.A.K.); kkang@ 123456gachon.ac.kr (K.S.K.); Tel.: + 82-44-860-6600 (B.A.K.); + 82-31-750-5402 (K.S.K.)
                [†]

                These authors contributed equally to this work.

                Article
                molecules-24-00464
                10.3390/molecules24030464
                6384830
                30696085
                © 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/).

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