ABSTRACT
Clinical treatment-failures to affordable drugs encouraged new investigation for discovery and development of new prophylactic and therapeutic interventions against malaria. The Drug Discovery Cluster (DDcl) of the Italian Malaria Network gathers several highly integrated and complementary laboratories from different Italian Institutions to identify, synthesise, screen in vitro and in vivo new antimalarial molecules directed against the intraerythrocytic stage of P. falciparum parasites and/or with transmission blocking activity to select lead compounds for further development. Complementary research activities, both in vitro and in the clinics, aim at investigating the pathogenetic mechanisms of severe malaria anaemia and the different manifestations of the disease in malaria-HIV co-infected patients to identify new therapies and improve survival.
Subject(s)
Antimalarials/pharmacology , Insecticides/pharmacology , Societies, Scientific/organization & administration , Animals , Anopheles/drug effects , Anopheles/metabolism , Anopheles/parasitology , Antimalarials/therapeutic use , Biological Products/pharmacology , Biological Products/therapeutic use , Drug Delivery Systems , Drug Design , Drug Evaluation, Preclinical , Drug Resistance , Humans , Insect Vectors/drug effects , Insect Vectors/metabolism , Insect Vectors/parasitology , Insecticides/therapeutic use , Italy , Kynurenine/metabolism , Malaria, Falciparum/drug therapy , Malaria, Falciparum/parasitology , Malaria, Falciparum/transmission , Mice , Mice, Inbred BALB C , Parasitic Sensitivity Tests , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Plasmodium falciparum/drug effectsABSTRACT
Secondary metabolites of the neem tree (Azadirachta indica A. Juss., Meliaceae) exhibit a wide range of biological activities in insects. However, few studies have addressed the effects of neem extracts or compounds in arthropods of medical importance. In this study, a laboratory strain of Anopheles stephensi was used to assess the effects of a commercial formulation (Neem Azal) (NA)), containing azadirachtin A at 34%, on blood feeding, oviposition and oocyte ultrastructure. Oral administration of Neem Azal) to A. stephensi females through artificial blood meals did impair blood intake and oviposition in a concentration dependent manner. Similar results were obtained on females, which had consumed Neem Azal) in sucrose solution before taking a blood meal of plain blood. Neem treated females displayed a delay in oocyte development in both the phase of vitellogenesis and the phase of choriogenesis. The ultrastructural studies on ovaries from Neem Azal) treated females revealed distinct structural modifications indicative of: (i) a complete block of oogenesis, (ii) impairment of vitellogenesis and vitelline envelope formation, (iii) a severe degeneration of follicle cells. In agreement with results obtained in other insects, this study indicates that Neem Azal) impairs hormone control of oogenesis and exerts a cytotoxic effect on both follicular cells and oocytes of the Asian malaria vector A. stephensi.