{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T10:00:28Z","timestamp":1773223228125,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Gansu Province","award":["25ZDFA001"],"award-info":[{"award-number":["25ZDFA001"]}]},{"name":"the Scientific Research Project of Gansu Province Higher Education Institutions","award":["2026CYZC-006"],"award-info":[{"award-number":["2026CYZC-006"]}]},{"name":"the project of Gansu Province Administration of Traditional Chinese Medicine","award":["GZKZ-2024-30"],"award-info":[{"award-number":["GZKZ-2024-30"]}]},{"name":"Science and Technology Program of Lanzhou","award":["2024-8-12"],"award-info":[{"award-number":["2024-8-12"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Toxoplasmosis is a zoonotic disease with limited therapeutic options, which are further hampered by significant toxicity and suboptimal efficacy. Effective interventions for chronic infection remain insufficient, and thus, natural product-derived drug screening remains a key focus in anti-Toxoplasma research. Licochalcone A (Lico A), a major bioactive compound isolated from Glycyrrhiza uralensis, exhibits potent activity against Toxoplasma tachyzoites. However, systematic studies of its targets, pharmacokinetics, and efficacy are lacking, hindering its development as an anti-Toxoplasma candidate drug. In this study, we used SPR-MS to identify 33 high-affinity target proteins (affinity score &gt; 1000). Furthermore, an AI-driven multidimensional analysis identified a cluster of five proteins (TgMORN1, D3XD37, ABCB2, MIC15, and IDH), with TgMORN1 yielding the highest composite score. RNAi experiments confirmed TgMORN1 as a key target, as its silencing attenuated the anti-proliferative effect of Lico A. Western blotting, NanoDSF, and SPR supported direct binding between Lico A and TgMORN1, suggesting that Lico A modulates TgMORN1 thermal stability through residues S168 and D203, with high species specificity. Pharmacokinetic evaluation revealed that Lico A had favorable absorption and blood\u2013brain barrier permeability, supporting its potential utility in treating brain disease. In vitro assays showed that Lico A effectively inhibited Toxoplasma gondii brain cyst formation. Collectively, these findings support Lico A as a promising candidate for the treatment of toxoplasmosis.<\/jats:p>","DOI":"10.3390\/biom16030410","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T12:39:08Z","timestamp":1773146348000},"page":"410","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Licochalcone A as a Potential Anti-Toxoplasma Agent: A Target Identification and Pharmacokinetic Study"],"prefix":"10.3390","volume":"16","author":[{"given":"Bing","family":"Li","sequence":"first","affiliation":[{"name":"School of Pharmacy, Lanzhou University, Lanzhou 730000, China"},{"name":"Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zexin","family":"Tao","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Lanzhou University, Lanzhou 730000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yichen","family":"Jing","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Lanzhou University, Lanzhou 730000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yubin","family":"Bai","sequence":"additional","affiliation":[{"name":"Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bintao","family":"Zhai","sequence":"additional","affiliation":[{"name":"Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6596-7907","authenticated-orcid":false,"given":"A. M.","family":"Abd El-Aty","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt"},{"name":"Department of Medical Pharmacology, Medical Faculty, Ataturk University, 25240 Erzurum, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangdi","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Lanzhou University, Lanzhou 730000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"ref_1","first-page":"523","article-title":"AN OVERVIEW OF CONGENITAL TOXOPLASMOSIS: CLINICAL FEATURES, DIAGNOSIS, TREATMENT AND PREVENTION","volume":"47","author":"Ahmad","year":"2017","journal-title":"J. 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