Schistosomiasis Control Using Piplartine against Biomphalaria glabrata at Different Developmental Stages

Background: Schistosomiasis is one of the most significant diseases in tropical countries and affects almost 200 million people worldwide. The application of molluscicides to eliminate the parasite's intermediate host, Biomphalaria glabrata, from infected water supplies is one strategy currently being used to control the disease. Previous studies have shown a potent molluscicidal activity of crude extracts from Piper species, with extracts from Piper tuberculatum being among the most active. Methods and Findings: The molluscicidal activity of P. tuberculatum was monitored on methanolic extracts from different organs (roots, leaves, fruit and stems). The compounds responsible for the molluscicidal activity were identified using 1H NMR and ESIMS data and multivariate analyses, including principal component analysis and partial least squares. These results indicated that the high molluscicidal activity displayed by root extracts (LC50 20.28 µg/ml) was due to the presence of piplartine, a well-known biologically-active amide. Piplartine was isolated from P. tuberculatum root extracts, and the molluscicidal activity of this compound on adults and embryos of B. glabrata was determined. The compound displayed potent activity against all developmental stages of B. glabrata. Next, the environmental toxicity of piplartine was evaluated using the microcrustacean Daphnia similis (LC50 7.32 µg/ml) and the fish Danio rerio (1.69 µg/ml). The toxicity to these organisms was less compared with the toxicity of niclosamide, a commercial molluscicide. Conclusions: The development of a new, natural molluscicide is highly desirable, particularly because the commercially available molluscicide niclosamide is highly toxic to some organisms in the environment (LC50 0.25 µg/ml to D. similis and 0.12 µg/ml to D. rerio). Thus, piplartine is a potential candidate for a natural molluscicide that has been extracted from a tropical plant species and showed less toxic to environment. Author Summary: Schistosomiasis is a disease caused by parasitic worms of several species of genus Schistosoma that affects almost 200 million people mostly common in Asia, Africa and South America. The transmission is carried out by the parasitic larvae hosted in fresh water snails of the genus Biomphalaria. Considering the socioeconomic importance of this disease, the management of the snail population in the lakes and fresh water sources is one strategy to control the schistosomiasis. Nowadays, one synthetic compound, niclosamide, is available, but it is considered toxic to other organisms in the environment. Thus in this work piplartine was evaluated as a new active natural molluscicide extracted from a tropical plant. In addition a fish Danio rerio and a microcrustacean Daphnia similis were used as model organisms to evaluate the environmental toxicity risk of piplartine that was less toxic compared to niclosamide in the experimental conditions.