Abstract
Schistosomiasis, a neglected tropical disease (NTD) caused by flatworms of the genus Schistosoma, affects more than 250 million people globally. Praziquantel (PZQ) remains the sole therapeutic option, underscoring the need for novel treatments. This study investigates the antischistosomal activity of Eremanthus erythropappus DC. MacLeish (Asteraceae) extracts, and their isolated compounds are against Schistosoma mansoni. In vitro assays revealed that the rinsed extract (LEE) exhibited a significantly lower EC(50) (18.1 μg/mL) compared to that of the ethanolic extract (EEE) (191.5 μg/mL), with no cytotoxicity observed at concentrations up to 500 μg/mL. UHPLC-ESI-MS/MS analysis annotated 16 metabolites, including sesquiterpene lactones (STLs) and pentacyclic triterpenoids. From LEE, friedelin (7), betulinic acid (8), and acacetin (14) were isolated, with the latter two being reported in E. erythropappus for the first time. Among them, only betulinic acid (8) demonstrated significant in vitro antischistosomal activity (EC(50) = 36.8 μM, SI > 15.5), while friedelin (7) and acacetin (14) were inactive (EC(50) > 50 μM). In S. mansoni-infected mice, the oral administration of betulinic acid (8) (400 mg/kg) reduced the worm burden by 41.9%, whereas LEE (400 mg/kg) achieved a substantial reduction in both the worm (∼86%) and egg burden (∼81%), also decreasing immature egg deposition by ∼87%. These findings highlight the promising antischistosomal potential of E. erythropappus, particularly LEE, warranting further studies to optimize the isolation and characterization of bioactive compounds.