Development of a pharmacodynamic screening model with Crithidia fasciculata

Abstract

The genus Crithidia is a member of the family Trypanosomatidae and is related to the genera Leishmania and Trypanosoma with which it shares a variety of biochemical mechanisms, such as polyamine synthesis and methionin salvage. In consequence, a screening system for antiparasitic candidate material has been developed with Crithidia fasciculata, a parasite naturally occurring in insects and amphibians, but devoid of pathogenicity for humans. Initially a variety of culture media were evaluated of which TPS was best suited for the maintenance of stock cultures, and E-medium - a newly developed formula - for sensitivity testing. Optimal growth of C. fasciculata was observed under microaerophilic conditions. A system for sensitivity testing was developed and applied to the investigation of extracts from higher tropical plants of the genera Stemona and Aglaia for anticrithidial activity. Extracts with significant anti-crithidial activity were scheduled for chromatographic fractionation and the subsequent isolation, purification and structural identification of individual compounds for further sensitivity testing. Encouraging results were obtained with extracts from Aglaia odorata leaves, A. elaeagnoidea stem bark and A. edulis leaves, with EC(90) values of 1213 ng/ml, 1606 ng/ml, and 1462 ng/ml, respectively.

Development of a pharmacodynamic screening model with Entamoeba histolytica

“…The study's focus on extracts from Aglaia edulis, Aglaia elaeagnoidea, Aglaia odorata and Stemona tu berosa can be explained by encouraging results in the Crithidia fasciculata model [11] and in malaria parasites. Particular aspects of the biological activity of alkaloids, stilbenoids and tocopherols from members of the family Stemonaceae have been explored before [15][16][17].…”

“…The extract formulations contained dry extract concentrations of 1.0 mg/ml or 5.0 mg/ml. The selection of the plants was based on earlier observations of bioactivity against protozoan parasites other than Entamoebidae [11]. For active control substances served metronidazole (Sigma M 1547), dehydroemetine bichlorhydrate (Ro-1-9334, Roche) and dihydroartemisinin (laboratory standard of the Academy of Military Medical Medicine, Beijing).…”

Punch in the gut: parasite tolerance of phytochemicals reflects host diet

“…However, C. fasciculata infects larvae as well as adults (Wallace, 1943). As a result, the parasite is likely exposed to a variety of phytochemicals in the woody debris-rich aquatic breeding habitats of mosquitoes, which are considered to be the major sites of C. fasciculata transmission (Clark et al, 1964), and has been proposed as a chemically resistant model for trypanosomatid protozoa that infect mammals (Tasanor et al, 2006;Siheri et al, 2016), with which its phytochemical tolerance is correlated (Siheri et al, 2016).…”