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A Multidimensional Evaluation of Sakuranetin against Schistosoma mansoni: From Drug-Likeness to In Vivo Efficacy
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DOI：10.1021/acsomega.6c03820.png)
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Abstract
En 中文
Schistosomiasis is a highly prevalent neglected tropical disease affecting more than 250 million people worldwide and currently relies on praziquantel (PZQ) as the only available treatment. This dependence raises concerns about the long-term sustainability of current control strategies and underscores the urgent need for new anthelmintic agents. In this context, natural products represent an important source of novel bioactive compounds. In the present study, the antischistosomal potential of sakuranetin (SAK), a flavanone isolated from Baccharis lateralis (Asteraceae), was evaluated. In silico analysis indicated favorable drug-like properties, including high predicted gastrointestinal absorption and absence of structural alerts. In vitro and in vivo safety assessments showed no cytotoxicity in Vero cells (CC50 > 500 μM) and no acute toxicity in Caenorhabditis elegans (LC50 > 1000 μM). When evaluated for direct antiparasitic effects, SAK did not exhibit detectable in vitro activity against adult Schistosoma mansoni worms. However, oral administration of SAK (400 mg/kg) in a S. mansoni murine model significantly reduced total worm burden by 84.4% and decreased fecal egg burden by 87.0% (PZQ: 88.2 and 95.9%, respectively). To support pharmacokinetic studies, a sensitive HPLC-UV method was validated (LLOQ = 50 ng/mL). SAK exhibited high plasma protein binding (unbound fraction = 8.3%) and was predominantly metabolized via glucuronidation in rat liver microsomes (t1/2 = 149 min). These findings support SAK as a promising natural product-derived lead with significant in vivo antischistosomal activity and favorable drug-like properties.
Keywords:
Anatomy
Pharmacokinetics
Plasma
Rodent models
Toxicity
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4.3
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