Schistosoma mansoni: In vitro schistosomicidal activity and tegumental alterations induced by piplartine on schistosomula

Abstract

Schistosomiasis is one of the most important parasitic infections in humans that occur in many tropical and subtropical countries. Currently, the control of schistosomiasis rests with a single drug, praziquantel, which is effective against adult worms but not the larval stages. Recent studies have shown that piplartine, an amide isolated from plants of the genus Piper (Piperaceae), reveals interesting antischistosomal properties against Schistosoma mansoni adult worms. Here, we report the in vitro antischistosomal activity of piplartine on S. mansoni schistosomula of different ages (3 h old and 1, 3, 5, and 7 days old), and examine alterations on the tegumental surface of worms by means of confocal laser scanning microscopy. Piplartine at a concentration of 7.5 μM caused the death of all schistosomula within 120 h. The lethal effect occurred in a dose-dependent manner and was also dependent on the age of the parasite. Microscopy observation revealed extensive tegumental destruction, including blebbing, granularity, and a shorter body length. This report provides the first evidence that piplartine is able to kill schistosomula of different ages and reinforce that piplartine is a promising compound that could be used for the development of new schistosomicidal agent.

Natural Products with Antischistosomal Activity

“…Piplartine (18) is an amide alkaloid found in several Piper species such as Piper tuberculatum. This compound has shown in vitro schistosomicidal activity against immature (3-hour-old and 1-, 3-, 5-and 7-day-old schistosomula) and adult S. mansoni worms [62,63]. Piplartine at 9.5 μM killed adult parasites (male and female coupled) and at sublethal concentration (6.3 μM) caused a 75% reduction in egg production.…”

“…Alkaloids are widely distributed in nature and they have been isolated from several plant species [17,18]. Piplartine [62,63], piperamide 1 [61], epiisopiloturine [49,84], sanguinarine [64], solamargine and solasonine [68] are alkaloids with in vitro antischistosomal properties. Mefloquine, an aminoalcohol derived from quinine, has in vitro and in vivo schistosomicidal activity (Figure 2) [57,58].…”

In vivo and In vitro of Arctiin Schistosomicidal Activity

“…The spread of schistosomiasis endemic areas and increasing infection rate [1][2][3][4][5][6][7][8][9] support the need of new drug discovery and development [5][6][7][8][9]. Research of natural products has provided remarkable new drugs or drug leads to combat several diseases [14][15][16][17][18].…”

“…Schistosoma mansoni (BH strain, Belo Horizonte, Brazil) worms were maintained in Biomphalaria glabrata snails as intermediate hosts and Mesocricetus auratus hamsters as definitive host at the Adolfo Lutz Institute (São Paulo, Brazil), according to standard procedures previously described [3,10]. At 50 days post infection, adult S. mansoni specimens were recovered from each hamster by perfusion in RPMI 1640 medium (Invitrogen, São Paulo, Brazil) supplemented with heparin.…”

“…According to World Health Organization (WHO) [2], schistosomiasis affects more than 240 million people in tropical and sub-tropical areas and more than 700 million are at risk of infection [3,4]. In Brazil, eight million people, from endemic regions stretching from the north to the south-east of the country, mainly in the Minas Gerais State, are infected with this chronic debilitating disease [3].…”