{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:38:50Z","timestamp":1790872730471,"version":"4.1.0"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T00:00:00Z","timestamp":1623369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p><jats:italic>Toxoplasma gondii<\/jats:italic> is an obligate intracellular pathogen that infects warm-blooded animals and humans. However, side effects limit toxoplasmosis treatment, and new drugs with high efficiency and low toxicity need to be developed. Natural products found in plants have become a useful source of drugs for toxoplasmosis. In this study, twenty natural compounds were screened for anti-<jats:italic>T. gondii<\/jats:italic> activity by Giemsa staining or real-time fluorescence quantitative polymerase chain reaction (qPCR) <jats:italic>in vitro<\/jats:italic>. Among these, licarin-B from nutmeg exhibited excellent anti-<jats:italic>T. gondii<\/jats:italic> activity, inhibiting <jats:italic>T. gondii<\/jats:italic> invasion and proliferation in a dose-dependent manner, with an EC<jats:sub>50<\/jats:sub> of 14.05 \u00b1 3.96 \u03bcg\/mL. In the <jats:italic>in vivo<\/jats:italic>, licarin-B treatment significantly reduced the parasite burden in tissues compared to no treatment, protected the 90% infected mice from to death at 50 mg\/kg.bw. Flow cytometry analysis suggested a significant reduction in <jats:italic>T. gondii<\/jats:italic> survival after licarin-B treatment. Ultrastructural changes in <jats:italic>T. gondii<\/jats:italic> were observed by transmission electron microscopy (TEM), as licarin-B induced mitochondrial swelling and formation of cytoplasmic vacuoles, an autophagosome-like double-membrane structure and extensive clefts around the <jats:italic>T. gondii<\/jats:italic> nucleus. Furthermore, MitoTracker Red CMXRos, MDC, and DAPI staining showed that licarin-B promoted mitochondrial damage, autophagosome formation, and nuclear disintegration, which were consistent with the TEM observations. Together, these findings indicate that licarin-B is a promising anti-<jats:italic>T. gondii<\/jats:italic> agent that potentially functions by damaging mitochondria and activating autophagy, leading to <jats:italic>T. gondii<\/jats:italic> death.<\/jats:p>","DOI":"10.3389\/fcell.2021.684393","type":"journal-article","created":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T11:21:51Z","timestamp":1623410511000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Licarin-B Exhibits Activity Against the Toxoplasma gondii RH Strain by Damaging Mitochondria and Activating Autophagy"],"prefix":"10.3389","volume":"9","author":[{"given":"Jili","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongfei","family":"Si","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhua","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jichao","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubin","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuzheng","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.3855\/jidc.4796","article-title":"Toxoplasmosis in immunocompromised patients in Iran: a systematic review and meta-analysis.","volume":"8","author":"Ahmadpour","year":"2014","journal-title":"J. Infect. Dev. Ctries."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1111\/j.1567-1364.2010.00659.x","article-title":"Mitophagy in yeast: actors and physiological roles.","volume":"10","author":"Bhatia-Kissova","year":"2010","journal-title":"FEMS Yeast Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/s0002-9394(02)01537-4","article-title":"A prospective, randomized trial of pyrimethamine and azithromycin vs pyrimethamine and sulfadiazine for the treatment of ocular toxoplasmosis.","volume":"134","author":"Bosch-Driessen","year":"2002","journal-title":"Am. J. Ophthalmol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e1233","DOI":"10.1128\/aac.01233-18","article-title":"Direct and indirect inhibition effects of resveratrol against toxoplasma gondii tachyzoites in vitro.","volume":"63","author":"Chen","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"B5","doi-asserted-by":"publisher","first-page":"314","DOI":"10.3109\/09273948.2011.608915","article-title":"Therapy for ocular toxoplasmosis.","volume":"19","author":"de-la-Torre","year":"2011","journal-title":"Ocul. Immunol. Inflamm."},{"key":"B6","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.jogoh.2017.12.003","article-title":"An updated literature review on maternal-fetal and reproductive disorders of Toxoplasma gondii infection.","volume":"47","author":"Fallahi","year":"2018","journal-title":"J. Gynecol. Obstet. Hum. Reprod."},{"key":"B7","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1111\/j.1462-5822.2011.01745.x","article-title":"Autophagy is a cell death mechanism in Toxoplasma gondii.","volume":"14","author":"Ghosh","year":"2012","journal-title":"Cell Microbiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"753","DOI":"10.3389\/fmicb.2018.00753","article-title":"Novel activity of a synthetic decapeptide against Toxoplasma gondii tachyzoites.","volume":"9","author":"Giovati","year":"2018","journal-title":"Front. Microbiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1093\/trstmh\/try040","article-title":"Ocular toxoplasmosis: adverse reactions to treatment in a Brazilian cohort.","volume":"112","author":"Guaraldo","year":"2018","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"B10","doi-asserted-by":"publisher","first-page":"9630","DOI":"10.1021\/acs.jafc.9b02173","article-title":"Synthesis and biological evaluation of (+)-usnic acid derivatives as potential anti-Toxoplasma gondii agents.","volume":"67","author":"Guo","year":"2019","journal-title":"J. Agric. Food Chem."},{"key":"B11","doi-asserted-by":"publisher","first-page":"e42107","DOI":"10.1371\/journal.pone.0042107","article-title":"Analysis of monensin sensitivity in Toxoplasma gondii reveals autophagy as a mechanism for drug induced death.","volume":"7","author":"Lavine","year":"2012","journal-title":"PLoS One"},{"key":"B12","first-page":"59","article-title":"Toxoplasmosis in immunocompromised patients.","volume":"64","author":"Machala","year":"2015","journal-title":"Epidemiol. Mikrobiol. Imunol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1006\/jsbi.2000.4228","article-title":"The single mitochondrion of tachyzoites of Toxoplasma gondii.","volume":"130","author":"Melo","year":"2000","journal-title":"J. Struct. Biol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"25","DOI":"10.3389\/fmicb.2017.00025","article-title":"A systematic review of in vitro and in vivo activities of anti-toxoplasma drugs and compounds (2006-2016).","volume":"8","author":"Montazeri","year":"2017","journal-title":"Front. Microbiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1089\/ars.2010.3799","article-title":"Targeting mitochondrial dysfunction: role for PINK1 and Parkin in mitochondrial quality control.","volume":"14","author":"Narendra","year":"2011","journal-title":"Antioxid. Redox Signal"},{"key":"B16","doi-asserted-by":"publisher","first-page":"7161","DOI":"10.1128\/aac.02009-15","article-title":"Clinically available medicines demonstrating anti-toxoplasma activity.","volume":"59","author":"Neville","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"B17","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.apcbee.2012.06.017","article-title":"Anti-parasitic activity of Myristica fragrans houtt. essential oil against toxoplasma gondii parasite.","volume":"2","author":"Pillai","year":"2012","journal-title":"APCBEE Procedia"},{"key":"B18","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1016\/S0002-9394(14)74456-3","article-title":"Therapy for ocular toxoplasmosis.","volume":"115","author":"Rothova","year":"1993","journal-title":"Am. J. Ophthalmol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"186","DOI":"10.2174\/1574891x10666150410120321","article-title":"Anti-toxoplasma activity of natural products: a review.","volume":"9","author":"Sepulveda-Arias","year":"2014","journal-title":"Recent Pat. Antiinfect. Drug Discov."},{"key":"B20","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.ijpddr.2018.02.006","article-title":"Licochalcone A: an effective and low-toxicity compound against Toxoplasma gondii in vitro and in vivo.","volume":"8","author":"Si","year":"2018","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e11733","DOI":"10.1371\/journal.pone.0011733","article-title":"HIV-1 inhibits autophagy in bystander macrophage\/monocytic cells through Src-Akt and STAT3.","volume":"5","author":"Van Grol","year":"2010","journal-title":"PLoS One"},{"key":"B22","author":"Weiss","year":"2013","journal-title":"Toxoplasma gondii: The Model Apicomplexan \u2013 Perspectives and Methods."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2152","DOI":"10.3389\/fmicb.2019.02152","article-title":"Myrislignan exhibits activities against Toxoplasma gondii RH strain by triggering mitochondrial dysfunction.","volume":"10","author":"Zhang","year":"2019","journal-title":"Front. Microbiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.ijpddr.2018.12.004","article-title":"New life for an old drug: in vitro and in vivo effects of the anthelmintic drug niclosamide against Toxoplasma gondii RH strain.","volume":"9","author":"Zhang","year":"2019","journal-title":"Int. J. Parasitol. Drugs Drug Resist."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.684393\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T11:21:56Z","timestamp":1623410516000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.684393\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,11]]},"references-count":24,"alternative-id":["10.3389\/fcell.2021.684393"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2021.684393","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,11]]},"article-number":"684393"}}