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      Screening of a library of traditional Chinese medicines to identify compounds and extracts which inhibit Toxoplasma gondii growth

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          Abstract

          Toxoplasma gondii can cause severe encephalitis in immunocompromised patients. Although pyrimethamine and sulphadiazine have been standard therapeutic agents for the treatment of acute toxoplasmosis, they have toxic side effects. Therefore, there is a need to identify new drugs that are less toxic. Some traditional Chinese medicines (TCMs) have shown good efficacy in controlling T. gondii replication in mouse models. Here, we screened a natural product library comprising TCMs with the aim of identifying compounds and extracts with anti-toxoplasmosis activities. We found several hit compounds and extracts that could be candidates for new drugs against T. gondii infection.

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          New therapeutic aspects of flavones: the anticancer properties of Scutellaria and its main active constituents Wogonin, Baicalein and Baicalin.

          Min Li‐Weber (2009)
          Traditional Chinese medicines have been recently recognized as a new source of anticancer drugs and new chemotherapy adjuvant to enhance the efficacy of chemotherapy and to ameliorate the side effects of cancer chemotherapies however their healing mechanisms are still largely unknown. Scutellaria baicalensis is one of the most popular and multi-purpose herb used in China traditionally for treatment of inflammation, hypertension, cardiovascular diseases, and bacterial and viral infections. Accumulating evidence demonstrate that Scutellaria also possesses potent anticancer activities. The bioactive components of Scutellaria have been confirmed to be flavones. The major constituents of Scutellaria baicalensis are Wogonin, Baicalein and Baicalin. These phytochemicals are not only cytostatic but also cytotoxic to various human tumor cell lines in vitro and inhibit tumor growth in vivo. Most importantly, they show almost no or minor toxicity to normal epithelial and normal peripheral blood and myeloid cells. The antitumor functions of these flavones are largely due to their abilities to scavenge oxidative radicals, to attenuate NF-kappaB activity, to inhibit several genes important for regulation of the cell cycle, to suppress COX-2 gene expression and to prevent viral infections. The tumor-selectivity of Wogonin has recently been demonstrated to be due to its ability to differentially modulate the oxidation-reduction status of malignant vs. normal lymphocytic cells and to preferentially induce phospholipase C gamma 1, a key enzyme involved in Ca(2+) signaling, through H(2)O(2) signaling in malignant lymphocytes. This review is aimed to summarize the research results obtained since the last 20 years and to highlight the recently discovered molecular mechanisms.
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            Toxoplasma invasion of mammalian cells is powered by the actin cytoskeleton of the parasite.

            J M Dobrowolski, L D Sibley (1996)
            Toxoplasma gondii is an obligate intracellular parasite that invades a wide range of vertebrate host cells. We demonstrate that invasion is critically dependent on actin filaments in the parasite, but not the host cell. Invasion into cytochalasin D (CD)-resistant host cells was blocked by CD, while parasite mutants invaded wild-type host cells in the presence of drug. CD resistance in Toxoplasma was mediated by a point mutation in the single-copy actin gene ACT1. Transfection of the mutant act1 allele into wild-type Toxoplasma conferred motility and invasion in the presence of CD. We conclude that host cell invasion by Toxoplasma, and likely by related Apicomplexans, is actively powered by an actin-based contractile system in the parasite.
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              Adverse Event Profile of Pyrimethamine-Based Therapy in Toxoplasmosis: A Systematic Review

              Ruben R. Ben-Harari, Elizabeth Goodwin, Julio Casoy (2017)
              Introduction Approximately a third of the population worldwide is chronically infected with Toxoplasma gondii. Pyrimethamine-based regimens are recommended for the treatment of toxoplasmosis. Objective The aim was to evaluate the safety profile of pyrimethamine-based treatment for the three main Toxoplasma manifestations: toxoplasmic encephalitis (TE), ocular toxoplasmosis, and congenital toxoplasmosis. Methods PubMed, Cochrane Library, and Google Scholar databases were searched through August 1, 2016. Randomized, observational, prospective/retrospective, and cohort studies were eligible. Thirty-one studies were included with a total of 2975 patients. Of these, 13 were in congenital toxoplasmosis (n = 929), 11 in ocular toxoplasmosis (n = 1284), and seven in TE (n = 687). Across manifestations, adverse event (AE)-related treatment discontinuation and/or change in therapy involved ≤37% of patients and occurred in >55% of studies: 100% for ocular toxoplasmosis, 57.1% for TE, and 61.5% for congenital toxoplasmosis. The most commonly observed AEs were bone marrow suppression, dermatologic, and gastrointestinal (GI). The prevalence of bone marrow suppression-related AEs was ≤50% in congenital toxoplasmosis, ≤42.7% in TE, and ≤9.0% in ocular toxoplasmosis. The frequency of GI and dermatologic AEs were ≤100 and ≤11.1%, respectively, for ocular toxoplasmosis, ≤10.7 and ≤17.9% for TE, and ≤10.8 and ≤2.1% for congenital toxoplasmosis. Steven–Johnson syndrome was reported in two patients with ocular toxoplasmosis and one with TE. Conclusion The AE profile associated with pyrimethamine-based treatments differed by each manifestation of toxoplasmosis and within a given manifestation. Hematologic AEs occurred across all manifestations indicating the importance of monitoring the blood of patients administered pyrimethamine-based regimens.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Vet Med Sci
                Journal ID (iso-abbrev): J. Vet. Med. Sci
                Journal ID (publisher-id): JVMS
                Title: The Journal of Veterinary Medical Science
                Publisher: The Japanese Society of Veterinary Science
                ISSN (Print): 0916-7250
                ISSN (Electronic): 1347-7439
                Publication date (Electronic): 02 January 2020
                Publication date (Print): February 2020
                Volume: 82
                Issue: 2
                Pages: 184-187
                Affiliations
                [1) ]National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan
                [2) ]Laboratory of Sustainable Animal Environment, Graduate School of Agricultural Science, Tohoku University, 232-3 Yomogida, Naruko-onsen, Osaki, Miyagi 989-6711, Japan
                Author notes
                [* ]Correspondence to: Kato, K.: kentaro.kato.c7@ 123456tohoku.ac.jp
                [#]

                These authors contributed equally to this work.

                Article
                Publisher ID: 19-0241
                DOI: 10.1292/jvms.19-0241
                PMC ID: 7041978
                PubMed ID: 31904004
                SO-VID: bc3afa4c-3691-4ba0-92c8-f2e0439a3458
                Copyright © ©2020 The Japanese Society of Veterinary Science
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License. (CC-BY-NC-ND 4.0: https://creativecommons.org/licenses/by-nc-nd/4.0/ )

                History
                Date received : 16 June 2019
                Date accepted : 12 December 2019
                Categories
                Subject: Parasitology
                Subject: Full Paper

                Keywords: acute toxoplasmosis,drug screening,toxoplasma gondii,traditional chinese medicine
                Data availability:
                Keywords: acute toxoplasmosis, drug screening, toxoplasma gondii, traditional chinese medicine

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