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This review summarizes current evidence on piplartine (piperlongumine), a naturally occurring amide from\n                    <jats:italic>Piper<\/jats:italic>\n                    species with broad antiparasitic and immunomodulatory properties. Studies on\n                    <jats:italic>Schistosoma mansoni<\/jats:italic>\n                    ,\n                    <jats:italic>Angiostrongylus cantonensis<\/jats:italic>\n                    ,\n                    <jats:italic>Leishmania<\/jats:italic>\n                    spp.,\n                    <jats:italic>Trypanosoma cruzi<\/jats:italic>\n                    ,\n                    <jats:italic>Trypanosoma brucei<\/jats:italic>\n                    ,\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    , and\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    demonstrate potent activity at micromolar levels, associated with disruption of parasite redox homeostasis. In host immune cells, piplartine modulates NF\u2010\u03baB and Nrf2 signaling, inhibits the immunoproteasome, and promotes antioxidant and anti\u2010inflammatory responses. These dual properties suggest that piplartine may influence both parasite survival and host immunopathology through redox\u2010sensitive mechanisms, although direct cause\u2013effect relationships during parasitic infection remain to be experimentally established. The compound\u2019s favorable drug\u2010likeness, oral bioavailability, and selective toxicity profile highlight its potential as a multitarget scaffold for the development of next\u2010generation therapeutics against neglected tropical and immune\u2010related diseases.\n                  <\/jats:p>","DOI":"10.1155\/jimr\/9793044","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T07:09:34Z","timestamp":1770275374000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Piplartine as an Innovative Natural Product With Dual Antiparasitic and Immunomodulatory Actions"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8829-7604","authenticated-orcid":false,"given":"Lucas","family":"Fukui-Silva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0028-6566","authenticated-orcid":false,"given":"Felipe C. 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