Trans-chalcone affects schistosomula and adult worms by impairing membrane integrity and attenuates the effects of Schistosoma mansoni-induced liver fibrosis

Schistosomiasis is an acute and chronic parasitic disease caused by helminths of the genus Schistosoma. The current treatment, praziquantel, is ineffective against immature forms and during granuloma formation in chronic phase. Chalcones belong to the flavonoid family and are known for their wide biological activities. Trans-Chalcone (TC), the thermodynamically stable isomeric form, exhibits anti-fibrotic and hepatoprotective effects in liver injury models. This study evaluates the in vitro and in vivo effects of TC on S. mansoni. In vitro, TC cytotoxicity was tested on LLC-MK2 cells, while schistosomula and adult worms were assessed for viability, oxidative stress, mitochondrial membrane potential, tegument integrity, morphological changes, and egg production. In vivo, S. mansoni-infected BALB/c mice received oral doses of TC (5, 10, and 20 mg/kg) for 15 days. Parasite burden, liver function (measuring NO, NAG, MPO, IL-12, IL-4, IL-13, and TGF-β), and hepatic histology (granuloma size, stage, and collagen deposition) were analyzed. TC reduced viability in normal cells only at high concentrations (175.60 and 264.90 μM). It was selective for juvenile (17.74 μM) and adult worms (50.00 μM), especially males. TC increased nitric oxide levels, altered mitochondrial and membrane integrity, and reduced egg laying in paired worms. In mice, TC improved liver function, reduced worm and egg counts, and altered granuloma area and profile, with lower levels of pro-inflammatory and pro-fibrotic cytokines, suggesting a modulatory effect on granuloma formation.