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      Botanical Medicines Cryptolepis sanguinolenta, Artemisia annua, Scutellaria baicalensis, Polygonum cuspidatum, and Alchornea cordifolia Demonstrate Inhibitory Activity Against Babesia duncani

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          Abstract

          Human babesiosis is a CDC reportable disease in the United States and is recognized as an emerging health risk in multiple parts of the world. The current treatment for human babesiosis is suboptimal due to treatment failures and unwanted side effects. Although Babesia duncani was first described almost 30 years ago, further research is needed to elucidate its pathogenesis and clarify optimal treatment regimens. Here, we screened a panel of herbal medicines and identified Cryptolepis sanguinolenta, Artemisia annua, Scutellaria baicalensis, Alchornea cordifolia, and Polygonum cuspidatum to have good in vitro inhibitory activity against B. duncani in the hamster erythrocyte model. Furthermore, we found their potential bioactive compounds, cryptolepine, artemisinin, artesunate, artemether, and baicalein, to have good activity against B. duncani, with IC 50 values of 3.4 μM, 14 μM, 7.4 μM, 7.8 μM, and 12 μM, respectively, which are comparable or lower than that of the currently used drugs quinine (10 μM) and clindamycin (37 μM). B. duncani treated with cryptolepine and quinine at their respective 1×, 2×, 4× and 8× IC 50 values, and by artemether at 8× IC 50 for three days could not regrow in subculture. Additionally, Cryptolepis sanguinolenta 90% ethanol extract also exhibited no regrowth after 6 days of subculture at doses of 2×, 4×, and 8× IC 50 values. Our results indicate that some botanical medicines and their active constituents have potent activity against B. duncani in vitro and may be further explored for more effective treatment of babesiosis.

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          Bioavailability of resveratrol.

          This paper reviews our current understanding of the absorption, bioavailability, and metabolism of resveratrol, with an emphasis on humans. The oral absorption of resveratrol in humans is about 75% and is thought to occur mainly by transepithelial diffusion. Extensive metabolism in the intestine and liver results in an oral bioavailability considerably less than 1%. Dose escalation and repeated dose administration of resveratrol does not appear to alter this significantly. Metabolic studies, both in plasma and in urine, have revealed major metabolites to be glucuronides and sulfates of resveratrol. However, reduced dihydroresveratrol conjugates, in addition to highly polar unknown products, may account for as much as 50% of an oral resveratrol dose. Although major sites of metabolism include the intestine and liver (as expected), colonic bacterial metabolism may be more important than previously thought. Deconjugation enzymes such as β-glucuronidase and sulfatase, as well as specific tissue accumulation of resveratrol, may enhance resveratrol efficacy at target sites. Resveratrol analogs, such as methylated derivatives with improved bioavailability, may be important in future research. © 2011 New York Academy of Sciences.
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            Human babesiosis.

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              Haem-activated promiscuous targeting of artemisinin in Plasmodium falciparum

              The mechanism of action of artemisinin and its derivatives, the most potent of the anti-malarial drugs, is not completely understood. Here we present an unbiased chemical proteomics analysis to directly explore this mechanism in Plasmodium falciparum. We use an alkyne-tagged artemisinin analogue coupled with biotin to identify 124 artemisinin covalent binding protein targets, many of which are involved in the essential biological processes of the parasite. Such a broad targeting spectrum disrupts the biochemical landscape of the parasite and causes its death. Furthermore, using alkyne-tagged artemisinin coupled with a fluorescent dye to monitor protein binding, we show that haem, rather than free ferrous iron, is predominantly responsible for artemisinin activation. The haem derives primarily from the parasite's haem biosynthesis pathway at the early ring stage and from haemoglobin digestion at the latter stages. Our results support a unifying model to explain the action and specificity of artemisinin in parasite killing.
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                Author and article information

                Contributors
                Journal
                Front Cell Infect Microbiol
                Front Cell Infect Microbiol
                Front. Cell. Infect. Microbiol.
                Frontiers in Cellular and Infection Microbiology
                Frontiers Media S.A.
                2235-2988
                08 March 2021
                2021
                : 11
                : 624745
                Affiliations
                [1] 1 Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University , Baltimore, MD, United States
                [2] 2 FOCUS Health Group, Naturopathic , Novato, CA, United States
                [3] 3 California Center for Functional Medicine , Kensington, CA, United States
                [4] 4 State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, China
                Author notes

                Edited by: Loïc Riviere, Université de Bordeaux, France

                Reviewed by: Chiranjib Pal, West Bengal State University, India; Laurence A. Marchat, Instituto Politécnico Nacional, Mexico

                *Correspondence: Ying Zhang, yzhang207@ 123456zju.edu.cn

                This article was submitted to Parasite and Host, a section of the journal Frontiers in Cellular and Infection Microbiology

                Article
                10.3389/fcimb.2021.624745
                7982592
                8d0a5646-654a-42e9-8597-6b906e28de8e
                Copyright © 2021 Zhang, Alvarez-Manzo, Leone, Schweig and Zhang

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 01 November 2020
                : 08 January 2021
                Page count
                Figures: 4, Tables: 2, Equations: 0, References: 136, Pages: 15, Words: 6866
                Categories
                Cellular and Infection Microbiology
                Original Research

                Infectious disease & Microbiology
                babesia duncani,cryptolepis sanguinolenta,herbal medicine,cryptolepine,artemisinin,baicalein,phytonutrient,phytotherapy

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