Plant-Derived Terpenes as Emerging Therapeutics Against Schistosomiasis

Schistosomiasis remains one of the most significant neglected tropical diseases (NTDs) worldwide, sustained by the complex biology of Schistosoma species and the host's immunopathological responses to tissue-trapped eggs. Despite decades of reliance on praziquantel (PZQ) as the sole chemotherapeutic option, major limitations persist, including its lack of activity against juvenile worms, incomplete protection against reinfection, and concerns regarding emerging tolerance. These challenges, together with persistent hotspots of transmission and uneven global progress toward disease elimination, underscore the urgent need for alternative or complementary therapies. Plant-derived terpenes have emerged as promising antischistosomal candidates due to their structural diversity, broad-spectrum bioactivity, and favourable safety profiles. Evidence from in vitro and in vivo studies demonstrates that monoterpenes, sesquiterpenes, diterpenes, triterpenes, and triterpenoid saponins exert multimodal effects on Schistosoma, including tegumental disruption, interference with metabolic and redox pathways, inhibition of oviposition, and modulation of host immune and fibrotic responses. Advances in mechanistic studies, supported by omics and computational approaches, further highlight their potential as leads for drug development. Additionally, nano-enabled delivery systems offer strategies to overcome pharmacokinetic limitations and enhance therapeutic performance. This review integrates current knowledge on schistosome biology, treatment challenges, and the growing evidence supporting terpenoids as viable components of a diversified antischistosomal therapeutic arsenal.