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. |
