{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:52:23Z","timestamp":1791363143232,"version":"4.3.1"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"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. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Alveolar echinococcosis (AE) is a severe parasitic disease caused by\n                      <jats:italic>Echinococcus multilocularis<\/jats:italic>\n                      . Current therapy relies mainly on benzimidazole drugs and is largely parasitostatic, highlighting the urgent need for new candidate compounds with improved efficacy. We hypothesized that isoalantolactone (ISO) exerts direct anti-\n                      <jats:italic>Echinococcus multilocularis<\/jats:italic>\n                      activity and evaluated whether ISO treatment was associated with changes in the lesion microenvironment and host immune responses during AE progression\n                      <jats:italic>in vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In vitro<\/jats:italic>\n                      experiments were conducted using isolated\n                      <jats:italic>Echinococcus multilocularis<\/jats:italic>\n                      protoscoleces, metacestode vesicles, and germinal layer cells, with assessments of protoscolex survival, phosphoglucose isomerase release, and germinal cell viability. Scanning and transmission electron microscopy, mitochondrial membrane potential detection, molecular docking, and protein expression analysis were also performed.\n                      <jats:italic>In vivo<\/jats:italic>\n                      efficacy was verified using a murine intraperitoneal infection model treated with ISO or albendazole, combined with evaluations of lesion burden, histopathology, safety indicators, immune cell subsets, and cytokine levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>ISO promoted phosphoglucose isomerase release, with a half-maximal effective concentration of 16.36 \u00b1 3.24 \u03bcM, and reduced germinal cell viability, with a half-maximal inhibitory concentration of 17.46 \u00b1 2.25\u00a0\u03bcM. It exerted dose- and time-dependent parasiticidal effects, achieving complete protoscolex death within 1\u20135 days at concentrations of 40\u00a0\u03bcM and 10\u00a0\u03bcM, respectively. In infected mice, ISO reduced lesion burden and spleen index and was associated with parasite structural damage, mitochondrial abnormalities, and changes in fibrosis-, inflammation-, and immune-related readouts under the present experimental conditions, with no marked abnormalities in most of the evaluated short-term safety parameters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      ISO shows anti-\n                      <jats:italic>Echinococcus multilocularis<\/jats:italic>\n                      activity\n                      <jats:italic>in vitro<\/jats:italic>\n                      and suppresses AE progression\n                      <jats:italic>in vivo<\/jats:italic>\n                      . Its activity was associated with parasite structural injury, mitochondrial membrane potential depolarization, and changes in the lesion microenvironment and host immune responses. Further preclinical evaluation of ISO as a candidate compound against AE is warranted.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1949982","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:24:21Z","timestamp":1791361461000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Isoalantolactone exhibits activity against Echinococcus multilocularis associated with mitochondrial perturbation and changes in the lesion microenvironment"],"prefix":"10.3389","volume":"17","author":[{"given":"Wei","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery, Qinghai University Affiliated Hospital (Clinical Medical College)","place":["Xining, Qinghai Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanchuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Central Laboratory, Qinghai University Affiliated Hospital (Clinical Medical College)","place":["Xining, Qinghai Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haining","family":"Fan","sequence":"additional","affiliation":[{"name":"General Surgery, Qinghai University Affiliated Hospital (Clinical Medical College)","place":["Xining, Qinghai Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1051\/parasite\/2024055","article-title":"Chemotherapy for the treatment of alveolar echinococcosis: where are we?","volume":"31","author":"Autier","year":"2024","journal-title":"Parasite"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1686956","DOI":"10.3389\/fmicb.2025.1686956","article-title":"Host angiogenic reprogramming by Echinococcus multilocularis protoscoleces protein via PDGFR\/PI3K\/AKT cascade","volume":"16","author":"Bi","year":"2025","journal-title":"Front. 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