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While conventional chemical fungicides offer effective control, their long-term use leads to increased fungicide resistance and poses risks to the environment and human health due to pesticide residues, underscoring the urgent need to develop novel fungicides. Artemisinin, first identified in Artemisia annua, is renowned for its antimalarial activity. Here, we demonstrate that artemisinin exhibites effective antifungal activity against Sclerotinia sclerotiorum with an EC50 value of 0.1 mg\/mL. Treatment with artemisinin caused the mycelia surface to collapse and shrivel, accompanied by enhanced membrane permeability. Pretreating Brassica napus and Arabidopsis leaves with artemisinin increased resistance to S. sclerotiorum infection. Proteomic analysis revealed that artemisinin treatment markedly downregulated the expression of key functional proteins in S. sclerotiorum, including enzymes involved in oxalic acid biosynthesis, cell wall-associated proteins, and secreted proteins. In conclusion, artemisinin exhibits notable inhibitory effects against S. sclerotiorum and may hold potential for development as a novel fungicide.<\/jats:p>","DOI":"10.3390\/ijms27083422","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T13:58:22Z","timestamp":1775829502000},"page":"3422","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Antifungal Activity and Biochemical Mechanisms of Artemisinin Against the Phytopathogen Sclerotinia sclerotiorum"],"prefix":"10.3390","volume":"27","author":[{"given":"Yuxin","family":"Zhao","sequence":"first","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"},{"name":"Department of Nephrology, Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People\u2019s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3014-6364","authenticated-orcid":false,"given":"Hai-Ning","family":"Lyu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Liao","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiale","family":"Xing","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7916-4012","authenticated-orcid":false,"given":"Xin","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanling","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyu","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3471-037X","authenticated-orcid":false,"given":"Junzhe","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoli","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengchao","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"},{"name":"Department of Nephrology, Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People\u2019s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, China"},{"name":"Graduate School of China Academy of Chinese Medical Sciences, Suzhou 215105, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0763-9574","authenticated-orcid":false,"given":"Xin","family":"Chai","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1111\/mpp.13221","article-title":"The evolutionary and molecular features of the broad-host-range plant pathogen S. sclerotiorum","volume":"23","author":"Derbyshire","year":"2022","journal-title":"Mol. 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