{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T10:46:53Z","timestamp":1782384413795,"version":"3.54.5"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"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. Vet. Sci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Cystic echinococcosis<\/jats:italic>\n                      , caused by\n                      <jats:italic>Echinococcus granulosus<\/jats:italic>\n                      larvae, is a prevalent global zoonotic parasitic disease that primarily invades the liver. Current clinical treatments are limited by unsatisfactory therapeutic efficacy and obvious adverse side effects, creating an urgent demand for safe and effective alternative therapeutic agents. Brucea javanica flavonoids are natural active ingredients with potential antiparasitic properties, and this study aimed to explore their anti-protoscolex activity, biosafety, and underlying molecular mechanism against\n                      <jats:italic>E. granulosus<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The optimal extraction process of\n                      <jats:italic>B. javanica<\/jats:italic>\n                      flavonoids was optimized via ethanol extraction method. In\n                      <jats:italic>vitro<\/jats:italic>\n                      pharmacological experiments were performed to detect the inhibitory effect of flavonoid extracts on\n                      <jats:italic>E. granulosus<\/jats:italic>\n                      protoscoleces. Scanning electron microscopy and Caspase-3 activity assay were used to observe morphological damage and apoptotic activation of protoscoleces. CCK-8 assay and acute oral LD\u2085\u2080 test were conducted to evaluate biosafety, while HE staining was applied for pathological observation of major organs. An\n                      <jats:italic>E. granulosus<\/jats:italic>\n                      -infected mouse model was established to verify in vivo therapeutic efficacy, and HE as well as Masson staining were used to assess lesion repair. Furthermore, UHPLC-HRMS metabolomics, Astral DIA proteomics, and molecular docking were combined to screen core active flavonoid monomers, and in vitro and in vivo experiments were implemented to verify the activity of key monomers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The optimal extraction conditions (80% ethanol, solid\u2013liquid ratio of 1:20, 60 \u00b0C for 30 min) yielded a flavonoid content of 10.72%. The crude flavonoid extract exerted a significant concentration-dependent inhibitory effect on protoscoleces, with an inhibition rate of 85.88% at 40 mg\/mL for 24 h. The extract severely damaged protoscolex ultrastructure and upregulated Caspase-3 activity by 4.22-fold to induce protoscolex apoptosis. Biosafety evaluation confirmed that 10 mg\/mL flavonoids had no obvious host cell toxicity, with a mouse oral LD\u2085\u2080 of 1.43 g\/kg and no pathological damage in major organs. In vivo results showed that 20 mg\/kg flavonoid treatment effectively reduced hepatic cyst numbers and promoted fibrotic repair in mice. Multi-omics analysis identified 50 flavonoid components and 25 differentially expressed proteins enriched in antiviral immune and RNA degradation pathways, and 16 flavonoids with high target-binding affinity were screened. Among them, myricetrin was the only active monomer, and 5 mg\/mL myricetrin glycoside treatment significantly reduced liver cyst volume and achieved effective parasite clearance and tissue repair in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This study systematically demonstrates the prominent anti-echinococcosis activity and good biosafety of B. javanica flavonoids both in vitro and in vivo. The flavonoids kill E. granulosus protoscoleces by destroying parasite structure and activating apoptotic pathways, and alleviate liver lesions by promoting tissue fibrosis repair. Myricetrin is identified as the core active substance responsible for the anti-parasitic effect. These findings reveal the material basis and potential mechanism of B. javanica against echinococcosis, filling the gap of natural anti-echinococcosis drug research. This work provides a reliable experimental basis for the development of novel safe and efficient anti-echinococcosis natural drugs, and offers a new strategy for the clinical treatment of cystic echinococcosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fvets.2026.1763947","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T09:51:19Z","timestamp":1782381079000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["In vitro screening of active flavonoid components from B. javanica flavonoids against protoscoleces of Echinococcus granulosus from sheep"],"prefix":"10.3389","volume":"13","author":[{"given":"Yueqi","family":"Yang","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Xinjiang Agricultural University","place":["Urumqi, Xinjiang, China"]},{"name":"Xin Jiang Key Laboratory of New Drug Researc and Development for Herbivorous Animals, Xinjiang Agricultural University","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medicine Institute, The First Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayinaer","family":"Jikesanbayi","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Xinjiang Agricultural University","place":["Urumqi, Xinjiang, China"]},{"name":"Xin Jiang Key Laboratory of New Drug Researc and Development for Herbivorous Animals, Xinjiang Agricultural University","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunlei","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Xinjiang Agricultural University","place":["Urumqi, Xinjiang, China"]},{"name":"Xin Jiang Key Laboratory of New Drug Researc and Development for Herbivorous Animals, Xinjiang Agricultural University","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Guo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medicine Institute, The First Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laizhen","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Xinjiang Agricultural University","place":["Urumqi, Xinjiang, China"]},{"name":"Xin Jiang Key Laboratory of New Drug Researc and Development for Herbivorous Animals, Xinjiang Agricultural University","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meihe","family":"Hu","sequence":"additional","affiliation":[{"name":"Yili Chuanning Biotechnology Co., Ltd.","place":["Yili, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songhan","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Xinjiang Agricultural University","place":["Urumqi, Xinjiang, China"]},{"name":"Xin Jiang Key Laboratory of New Drug Researc and Development for Herbivorous Animals, Xinjiang Agricultural University","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahao","family":"Zhai","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Xinjiang Agricultural University","place":["Urumqi, Xinjiang, China"]},{"name":"Xin Jiang Key Laboratory of New Drug Researc and Development for Herbivorous Animals, Xinjiang Agricultural University","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Wei","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Xinjiang Agricultural University","place":["Urumqi, Xinjiang, China"]},{"name":"Xin Jiang Key Laboratory of New Drug Researc and Development for Herbivorous Animals, Xinjiang Agricultural University","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luheng","family":"Xiao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Xinjiang Agricultural University","place":["Urumqi, Xinjiang, China"]},{"name":"Xin Jiang Key Laboratory of New Drug Researc and Development for Herbivorous Animals, Xinjiang Agricultural University","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Xin Jiang Key Laboratory of New Drug 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