Dose-response relationship in Schistosoma mansoni juvenile and adult stages following limonin treatment in experimentally infected mice.

Preventive chemotherapy with praziquantel is the mainstay of schistosomiasis control. However, drug resistance is an imminent threat, particularly with large-scale administration of praziquantel, in addition to much less efficacy against young schistosomes. Several biological activities of limonin have been explored such as insecticidal, insect antifeedant, and growth-regulating activity on insects as well as antimalarial, antiviral, anticancer, cholesterol-lowering, and antioxidant activities. This study investigates limonin as an alternative antischistosomal compound using two novel, single, oral dose regimens. In the current work, the therapeutic efficacy of different limonin dosing protocols was evaluated in experimentally infected mice harboring Schistosoma mansoni (Egyptian strain) juvenile or adult stages. Oral administration of limonin in a single dose of 50 or 100 mg/kg on day 21 post-infection (p.i.) resulted in a significant worm burden reduction of 70.0 and 83.33 %, respectively. The same dose given on day 56 p.i. reduced total worm burdens by 41.09 and 60.27 %, respectively. In addition, significant reductions of 34.90 and 47.16 % in the hepatic and 46.67 and 56.1 % in the intestinal tissue egg loads, respectively, associated with significant alterations in the oogram pattern with elevated dead egg levels. Limonin produced ameliorations of hepatic pathology with reduction in dimensions and number of granulomas. Limonin also produced a variety of tegumental alterations in treated worms including tubercular disruption, edema, blebbing, and ulcerations. Results obtained by this work elucidated promising limonin bioactivity against S. mansoni juvenile and adult stages and provided a basis for subsequent experimental and clinical trials.

In Vitro Schistosomicidal Activity of Phytol and Tegumental Alterations Induced in Juvenile and Adult Stages of Schistosoma haematobium.

There is renewed interest in natural products as a starting point for discovery of drugs for schistosomiasis. Recent studies have shown that phytol reveals interesting in vivo and in vitro antischistosomal properties against Schistosoma mansoni adult worms. Here, we report the in vitro antischistosomal activity of phytol against Schistosoma haematobium juvenile and adult worms and alterations on the tegumental surface of the worms by means of scanning electron microscopy. The assay, which was carried out with 6 concentrations (25, 50, 75, 100, 125, and 150 µg/ml) of phytol, has shown a promising activity in a dose and time-dependent manner. There was a significant decline in the motility of the worms and a mortality rate of 100% was found at 48 hr after they had been exposed to phytol in the concentration of 150 µg/ml. Male worms were more susceptible. On the ultrastructural level, phytol also induced tegumental peeling, disintegration of tubercles and spines in addition to morphological disfiguring of the oral and ventral suckers. This report provides the first evidence that phytol is able to kill S. haematobium of different ages, and emphasizes that it is a promising natural product that could be used for development of a new schistosomicidal agent.