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Synriam (SYN), an antimalarial medication, has showed promises against schistosomiasis, although in vivo research on its efficacy in preventing infection-related consequences has not been thoroughly explored. This study looked at the effectiveness of SNY-PZQ combination treatment against <jats:italic>Schistosoma mansoni<\/jats:italic> in mice at various developmental phases, including juvenile (schistosomula) and mature stages. Worm load, egg deposition, parasite maturity, and liver histology were among the key outcomes evaluated. Their modulatory effects on liver injury indicators, proinflammatory cytokines, CYP450 enzymes, and apoptosis in mice infected with mature <jats:italic>S. mansoni<\/jats:italic> were also investigated. The study was divided into two experimental batches: schistosomula and mature stages, with infected mice from each batch divided into five groups to evaluate SNY, PZQ, and their combination. The SNY-PZQ combination was administered 3 weeks post-infection (PI) for schistosomula-stage infection, and 7 weeks PI for mature-stage infection. When SYN is combined with PZQ in their sub-curative doses (SC), it strengthens the worm killing effects, making it more potent than giving PZQ alone (SC), especially when the dual treatment was given against 7-weeks mature worms (95% vs. 76% for PZQ SC). This was accompanied with almost total eggs elimination and the repair of hepatic granulomatous lesions. Nevertheless, this combination therapy has moderate effectiveness (47% vs. 13% for PZQ SC) when given against 3-weeks juvenile worms. Furthermore, administering this combined therapy to 7-weeks mature worms reduces liver damage as evidenced by decreased oxidative stress, inflammation, and apoptosis, as well as normalization of liver serum enzymes, when compared to PZQ alone, implying that they may contribute to liver fibrosis prevention. Overall, SYN, when combined with PZQ, could improve treatment efficacy, potentially overcoming drug failures, offering a cost-effective strategy for managing schistosomiasis in resource-limited countries.<\/jats:p>","DOI":"10.1038\/s41598-025-14037-5","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T05:27:54Z","timestamp":1754544474000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Optimizing the therapeutic benefits of synriam combined with praziquantel in mice harbouring juvenile and mature Schistosoma mansoni"],"prefix":"10.1038","volume":"15","author":[{"given":"Abdel-Nasser A.","family":"Sabra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha B.","family":"Salem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samia","family":"William","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olfat A.","family":"Hammam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naglaa M.","family":"El-Lakkany","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,7]]},"reference":[{"key":"14037_CR1","unstructured":"WHO. 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