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      Trichosanthes tricuspidata Lour. Methanol Extract Exhibits Anti-Inflammatory Activity by Targeting Syk, Src, and IRAK1 Kinase Activity

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          Abstract

          Trichosanthes tricuspidata Lour., also known as T. palmata Roxb, T. bracteata Lam., T. puber Blume, and Modecca bracteata, is a vine belonging to the Cucurbitaceae family (English name: redball snake gourd). Distributed in China, South and East Asia, and tropical Australia, it has been traditionally used as a medicinal plant for its antifever, laxative, anthelmintic properties and for migraine treatment. In this paper, we examined the effects of Trichosanthes tricuspidata Lour. ethanol extract (Tt-ME) in vitro and in vivo. To confirm the effects of Tt-ME on inflammatory responses, we conducted experimental analyses including level of nitric oxide (NO) production, RT-PCR, and immunoblotting and using a HCl/EtOH-induced gastritis animal model. Tt-ME attenuated the release of NO and decreased mRNA levels of inducible NO synthase (iNOS), TNF- α, and IL-6 in lipopolysaccharide- (LPS-) induced macrophages in a concentration-dependent manner. Tt-ME time-dependently suppressed nuclear translocation of nuclear factor kappa B (NF- κB) subunits p50 and p65, activator protein (AP-1) subunits c-Fos and c-Jun, and STAT3 transcriptional activity by inhibiting nuclear translocation of p50, p65, c-Fos, c-Jun, and STAT3. Tt-ME significantly downregulated NF- κB, MAPK, and JAK2 signaling by targeting Syk, Src, and IRAK1 protein kinases. Furthermore, matrix metalloproteinase-9 (MMP-9) expression and cell migration were observed to be downregulated by Tt-ME in LPS-activated macrophages. In vivo studies on Tt-ME also produced similar trends in Hcl/EtOH-induced gastritis mouse models by inhibiting proinflammatory cytokines and the inflammatory signaling pathway. Our results strongly suggest that Tt-ME exerted anti-inflammatory activity in LPS-stimulated macrophages and mouse models of acute inflammatory disease.

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          Rapid and automated tetrazolium-based colorimetric assay for the detection of anti-HIV compounds.

          A rapid, sensitive and automated assay procedure was developed for the in vitro evaluation of anti-HIV agents. An HTLV-I transformed T4-cell line, MT-4, which was previously shown by Koyanagi et al. (1985) to be highly susceptible to, and permissive for, HIV infection, served as the target cell line. Inhibition of the HIV-induced cytopathic effect was used as the end point. The viability of both HIV- and mock-infected cells was assessed spectrophotometrically via the in situ reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The procedure was optimized as to make optimal use of multichannel pipettes, microprocessor-controlled dispensing and optical density reading. The absorbance ratio of the mock-infected control to the HIV-infected samples was about 20. This allowed an accurate determination of the 50% effective doses, as demonstrated for 3'-azido-2',3'-dideoxythymidine (AZT), 2',3'-dideoxycytidine (ddCyd), dextran sulfate and heparin. The technique significantly reduced labor time as compared to the trypan blue exclusion method, and permits the evaluation of large numbers of compounds for their anti-HIV activity.
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            Nuclear interaction of EGFR and STAT3 in the activation of the iNOS/NO pathway.

            Epidermal growth factor receptor (EGFR) exists in the nucleus of highly proliferative cells where it functions as a transcription factor. Although EGFR has transactivational activity, it lacks a DNA binding domain and, therefore, may require a DNA binding transcription cofactor for its transcriptional function. Here, we report that EGFR physically interacts with signal transducers and activators of transcription 3 (STAT3) in the nucleus, leading to transcriptional activation of inducible nitric oxide synthase (iNOS). In breast carcinomas, nuclear EGFR positively correlates with iNOS. This study describes a mode of transcriptional control involving cooperated efforts of STAT3 and nuclear EGFR. Our work suggests that the deregulated iNOS/NO pathway may partly contribute to the malignant biology of tumor cells with high levels of nuclear EGFR and STAT3.
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              LPS-induced cytokine production in human monocytes and macrophages.

              Lipopolysaccharide (LPS) from Gram-negative bacteria is one of the most potent innate immune-activating stimuli known. Here we review the current understanding of LPS effects on human monocyte and macrophage function. We provide an overview of LPS signal transduction with attention given to receptor cooperativity and species differences in LPS responses, as well as the role of tyrosine phosphorylation and lysine acetylation in signalling. We also review LPS-regulated transcription, with emphasis on chromatin remodeling and primary versus secondary transcriptional control mechanisms. Finally, we review the regulation and function of LPS-inducible cytokines produced by human monocytes and macrophages including TNFα, the IL-1 family, IL-6, IL-8, the IL-10 family, the IL-12 family, IL-15 and TGFβ.
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                Author and article information

                Contributors
                Journal
                Evid Based Complement Alternat Med
                Evid Based Complement Alternat Med
                ECAM
                Evidence-based Complementary and Alternative Medicine : eCAM
                Hindawi
                1741-427X
                1741-4288
                2019
                16 December 2019
                16 December 2019
                : 2019
                : 6879346
                Affiliations
                1Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea
                2School of Systems Biomedical Science, Soongsil University, Seoul 06978, Republic of Korea
                Author notes

                Academic Editor: Caigan Du

                Author information
                https://orcid.org/0000-0003-0063-5025
                https://orcid.org/0000-0001-7440-5025
                https://orcid.org/0000-0001-8141-9927
                Article
                10.1155/2019/6879346
                6942823
                385c9062-80d4-4244-9f72-6777ee128335
                Copyright © 2019 Akash Ahuja et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 7 November 2019
                : 27 November 2019
                Funding
                Funded by: Ministry of Education
                Award ID: 2017R1A6A1A03015642
                Categories
                Research Article

                Complementary & Alternative medicine
                Complementary & Alternative medicine

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