{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T03:16:08Z","timestamp":1785208568173,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0013815","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000}}],"reference-count":30,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471850"],"award-info":[{"award-number":["82471850"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82002157"],"award-info":[{"award-number":["82002157"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012217","name":"Xuzhou Medical University","doi-asserted-by":"publisher","award":["JBGS202202"],"award-info":[{"award-number":["JBGS202202"]}],"id":[{"id":"10.13039\/501100012217","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Jiangsu Provincial Government Scholarship for Overseas Study Funding"},{"DOI":"10.13039\/501100012217","name":"Xuzhou Medical University","doi-asserted-by":"publisher","award":["2024BMS28"],"award-info":[{"award-number":["2024BMS28"]}],"id":[{"id":"10.13039\/501100012217","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Plant-derived natural products have emerged as promising candidates for developing novel anti-toxoplasmosis drugs. This study aimed to elucidate the role and mechanism of the phytochemical arbutin in the control of\n                      <jats:italic>T. gondii<\/jats:italic>\n                      infection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methodology\/Principal findings<\/jats:title>\n                    <jats:p>\n                      The effect of arbutin on\n                      <jats:italic>T. gondii<\/jats:italic>\n                      infection and host inflammatory response was evaluated both in vitro and in vivo. RNA-seq was performed on mouse bone marrow-derived macrophage samples to identify potential arbutin-related biological processes and molecular targets that control\n                      <jats:italic>T. gondii<\/jats:italic>\n                      infection. These targets were further confirmed using target-specific activators or inhibitors. Our data indicated that arbutin has dual therapeutic effects against\n                      <jats:italic>T. gondii<\/jats:italic>\n                      infection through concurrently controlling parasite growth and mitigating infection-induced inflammation. Mechanistically, arbutin mediates restriction of intracellular labile iron pool in both immune and non-immune cells, thereby depriving the parasite of essential metal nutrients. In addition, in macrophages, arbutin not only inhibits infection-induced inflammatory response but also upregulates the expression of heme degrading enzyme heme oxygenase-1, which facilitates biliverdin production. Our data further demonstrated that biliverdin exhibits anti-\n                      <jats:italic>T. gondii<\/jats:italic>\n                      effector function. Furthermore, arbutin is also effective in reducing infection-related mortality in immunocompromised mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions\/Significance<\/jats:title>\n                    <jats:p>Our data highlight arbutin\u2019s potential therapeutic value in fighting against acute hyperinflammatory phase of Toxoplasmosis even in immunocompromised host but also its limitation in establishing long-term immunity. Our study further suggests a potential direction for further development of effective drugs to prevent and treat toxoplasmosis by pharmacologically enhancing cell-autonomous defense mechanisms while suppressing inflammatory response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pntd.0013815","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T18:43:03Z","timestamp":1765478583000},"page":"e0013815","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["The phytochemical arbutin exerts potent anti-Toxoplasma effects through activation of cell-autonomous defense mechanisms while attenuating 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