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.
Department of Parasitology, Faculty of Medicine, Benha University, Benha, 13518, Egypt. maysa.hassan@fmed.bu.edu.eg.
Maysa Ahmad
MA
Eraky
Department of Parasitology, Faculty of Medicine, Benha University, Benha, 13518, Egypt.
Asmaa Abd El-Monem
AA
El-Kholy
Department of Parasitology, Faculty of Medicine, Benha University, Benha, 13518, Egypt.
Gehan Abd El-Rahman
GA
Rashed
Department of Pathology, Theodore Bilharz Research Institute, Giza, Egypt.
Olfat Ali
OA
Hammam
Department of Parasitology, Faculty of Medicine, Benha University, Benha, 13518, Egypt.
Ahlam Farag
AF
Moharam
Department of Parasitology, Faculty of Medicine, Benha University, Benha, 13518, Egypt.
Eman Abdel-Rahman
EA
Abou-Ouf
Department of Parasitology, Faculty of Medicine, Benha University, Benha, 13518, Egypt.
Nagwa Shaban Mohammed
NS
Aly
Department of Parasitology, Faculty of Medicine, Benha University, Benha, 13518, Egypt.
Shereen Magdy
SM
Kishik
Medical Parasitology Department, College of Medicine, Taif University, Taif, Saudi Arabia.
Karim Fetouh
KF
Abdallah
Department of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.
Dalia Ibrahim
DI
Hamdan
D000284:Administration, Oral; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D006099:Granuloma / Q000469:parasitology / Q000473:pathology; D007422:Intestines / Q000469:parasitology / Q000473:pathology; D036701:Limonins / Q000008:administration & dosage*; D008099:Liver / Q000469:parasitology / Q000473:pathology; D008297:Male; D051379:Mice; D010270:Parasite Egg Count; D011223:Praziquantel / Q000008:administration & dosage*; D012550:Schistosoma mansoni / Q000187:drug effects*; D012555:Schistosomiasis mansoni / Q000188:drug therapy* / Q000469:parasitology; D012556:Schistosomicides / Q000008:administration & dosage*
D036701:Limonins; D012556:Schistosomicides; D011223:Praziquantel; C001546:limonin
Adult; In vivo; Juvenile; Limonin; Natural plants; S. mansoni