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      Dietary Supplementation with Sea Bass ( Lateolabrax maculatus) Ameliorates Ulcerative Colitis and Inflammation in Macrophages through Inhibiting Toll-Like Receptor 4-Linked Pathways

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          Abstract

          Sea bass ( Lateolabrax maculatus) is a kind of food material commonly consumed in daily life. In traditional Chinese medicinal books, it has been indicated that sea bass can be applied for managing many inflammation-associated conditions. However, the studies on the pharmacological mechanisms of inflammation of sea bass remain scarce. Hence, this study aims to investigate the molecular mechanisms of the anti-inflammatory activity of sea bass. Anti-inflammatory activities of sea bass were assessed using dextran sulfate sodium (DSS)-induced colitis in a mice model and lipopolysaccharide (LPS)-activated macrophages model. Low body weight and short colon length were observed in DSS-fed mice that were significantly recovered upon sea bass treatments. Moreover, the colon histopathology score showed that sea bass-treated mice had decreased crypt damage, focal inflammation infiltration and the extent of inflammation, suggesting that treatment with sea bass could attenuate intestinal inflammation. In addition, the in-vitro study conjointly indicated that sea bass could suppress the inflammatory mediators in LPS-activated macrophage by inhibiting the TLR4-linked pathway. The present findings demonstrated that sea bass has an inhibitory effect on TLR4 signaling; thus, it could be a promising candidate for treating inflammation-associated conditions. A further justification for the clinical application of sea bass in treating inflammation-associated conditions is necessary.

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          Most cited references40

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          A microbial symbiosis factor prevents intestinal inflammatory disease.

          Humans are colonized by multitudes of commensal organisms representing members of five of the six kingdoms of life; however, our gastrointestinal tract provides residence to both beneficial and potentially pathogenic microorganisms. Imbalances in the composition of the bacterial microbiota, known as dysbiosis, are postulated to be a major factor in human disorders such as inflammatory bowel disease. We report here that the prominent human symbiont Bacteroides fragilis protects animals from experimental colitis induced by Helicobacter hepaticus, a commensal bacterium with pathogenic potential. This beneficial activity requires a single microbial molecule (polysaccharide A, PSA). In animals harbouring B. fragilis not expressing PSA, H. hepaticus colonization leads to disease and pro-inflammatory cytokine production in colonic tissues. Purified PSA administered to animals is required to suppress pro-inflammatory interleukin-17 production by intestinal immune cells and also inhibits in vitro reactions in cell cultures. Furthermore, PSA protects from inflammatory disease through a functional requirement for interleukin-10-producing CD4+ T cells. These results show that molecules of the bacterial microbiota can mediate the critical balance between health and disease. Harnessing the immunomodulatory capacity of symbiosis factors such as PSA might potentially provide therapeutics for human inflammatory disorders on the basis of entirely novel biological principles.
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            Host-derived nitrate boosts growth of E. coli in the inflamed gut.

            Changes in the microbial community structure are observed in individuals with intestinal inflammatory disorders. These changes are often characterized by a depletion of obligate anaerobic bacteria, whereas the relative abundance of facultative anaerobic Enterobacteriaceae increases. The mechanisms by which the host response shapes the microbial community structure, however, remain unknown. We show that nitrate generated as a by-product of the inflammatory response conferred a growth advantage to the commensal bacterium Escherichia coli in the large intestine of mice. Mice deficient in inducible nitric oxide synthase did not support the growth of E. coli by nitrate respiration, suggesting that the nitrate generated during inflammation was host-derived. Thus, the inflammatory host response selectively enhances the growth of commensal Enterobacteriaceae by generating electron acceptors for anaerobic respiration.
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              Indirubin Inhibits LPS-Induced Inflammation via TLR4 Abrogation Mediated by the NF-kB and MAPK Signaling Pathways.

              Indirubin plays an important role in the treatment of many chronic diseases and exhibits strong anti-inflammatory activity. However, the molecular mode of action during mastitis prophylaxis remains poorly understood. In this study, a lipopolysaccharide (LPS)-induced mastitis mouse model showed that indirubin attenuated histopathological changes in the mammary gland, local tissue necrosis, and neutrophil infiltration. Moreover, indirubin significantly downregulated the production of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α). We explored the mechanism whereby indirubin exerts protective effects against LPS-induced inflammation of mouse mammary epithelial cells (MMECs). The addition of different concentrations of indirubin before exposure of cells to LPS for 1 h significantly attenuated inflammation and reduced the concentrations of the three inflammatory cytokines in a dose-dependent manner. Indirubin downregulated LPS-induced cyclooxygenase-2 (COX-2) and Toll-like receptor 4 (TLR4) expression, inhibited phosphorylation of the LPS-induced nuclear transcription factor-kappa B (NF-kB) P65 protein and its inhibitor IkBα of the NF-kB signaling pathway. Furthermore, indirubin suppressed phosphorylation of P38, extracellular signal-regulated kinase (ERK), and c-Jun NH2-terminal kinase (JNK) of the mitogen-activated protein kinase (MAPK) signal pathways. Thus, indirubin effectively suppressed LPS-induced inflammation via TLR4 abrogation mediated by the NF-kB and MAPK signaling pathways and may be useful for mastitis prophylaxis.
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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
                14 June 2019
                June 2019
                : 20
                : 12
                : 2907
                Affiliations
                [1 ]Programme of Food Science and Technology, Division of Science and Technology, Beijing Normal University-Hong Kong Baptist University United International College, Zhuhai 519087, China; kellychan123@ 123456126.com (J.C.); jmkbio@ 123456uic.edu.hk (M.J.); l630013050@ 123456mail.uic.edu.hk (W.Z.); j430013005@ 123456mail.uic.edu.hk (L.C.)
                [2 ]Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China
                [3 ]Hebei Key Laboratory of Natural Products Activity Components and Function, Hebei Normal University of Science and Technology, Qinhuangdao 066004, China; bindufood@ 123456aliyun.com
                Author notes
                [* ]Correspondence: zlyu@ 123456hkbu.edu.hk (Z.Y.); baojunxu@ 123456uic.edu.hk (B.X.); Tel.: +852-34112465 (Z.Y.); +86-756-3620636 (B.X.)
                Author information
                https://orcid.org/0000-0002-7317-4146
                https://orcid.org/0000-0003-0739-3735
                Article
                ijms-20-02907
                10.3390/ijms20122907
                6628281
                31207873
                1ec4ac81-d1ea-4939-9374-90ff03743877
                © 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
                : 25 May 2019
                : 12 June 2019
                Categories
                Article

                Molecular biology
                inflammation,ulcerative colitis,dietary therapy,tlr4 signaling
                Molecular biology
                inflammation, ulcerative colitis, dietary therapy, tlr4 signaling

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