Development of a pharmacodynamic screening model with Entamoeba histolytica

Abstract

Human amoebiasis caused by Entamoeba histolytica is widely distributed in the tropics and subtropics, but also occurring in neighbouring parts of the temperate zones. Invasive amoebiasis causes dysentery and, by haematogenous spread, also extra-intestinal hepatic, pulmonary or cerebral abscesses, not rarely fatal conditions. The available anti-amoebic drugs have shortcomings regarding tolerability and efficacy. To facilitate the screening of candidate material, an in vitro system has been developed that permits the determination of specific anti-amoebic activity. PYE medium, supplemented with bovine serum, proved to be suitable for the maintenance of the stock cultures of Entamoeba histolytica strain HM1:1MSS. For sensitivity testing, Waymouth medium and cultivation under aerobic conditions were most reliable. After adapting the system to the use of 96-well (8 x 12) tissue culture plates, sensitivity tests were carried out with metronidazole, dehydroemetine and dihydroartemisinin as active control drugs, and seven extracts from Stemona tuberosa, Aglaia edulis, Aglaia elaeagnoidea and Aglaia odorata. Stem bark extract from Aglaia elaeagnoidea was the most active material with an IC(99) of 496 ng/ml and a slope S of 1.1325, followed by leaf extract from Stemona tuberosa with an IC(99) of 638 ng/ml and a slope S of 1.5648. All seven extracts showed full activity at concentrations <4000 ng/ml and qualified for further investigation.

A phenolic ester from Aglaia loheri leaves reveals cytotoxicity towards sensitive and multidrug-resistant cancer cells

“…This group of compounds was found to be effective against thymidine kinase-deficient Herpes simplex virus type 1 (HSV-1) and phosphonoacetate-resistant HSV-1 strains [9], including human amoebiasis caused by Entamoeba histolytica [10]. These compounds were shown to inhibit necrosis factor (NF)-B induced gene activation in human T cells [11], HIV-1 infection [12], and initiation and promotion of chemically-induced cancer on mouse skin [13].…”

Comparison of allopathic and herbal medicine for the treatment of Entamoeba histolytica: A double blind clinical trial

“…Traditionally, metronidazole is prescribed for the treatment of amoebiasis and taken as drug of choice (Tasanor, 2007;Gupta, 2004;Khairnar, 2007) but studies have shown that it is not effective against the cyst, as it is rapidly absorbed from the lumen (Powell, 1969). The present recommendations are to combine this drug with some luminal amoebicidal like paromycin or diloxanide furoate.…”

“…About 25% patients were passing cyst even after completing the full course of therapy in both the groups with no significant difference between the two treatment groups. Tasanor (2007) tested in vitro three of the allopathic drugs as control (Metronidazole, Dehydroemetine and Dihydroartiminisin) and seven herbs (leaves, root and stem bark of Agalia eleagnoidae (Ae), leaves from Stemona tuberose (St), stem bark and leaves of Agalia odutis (Ao), and leaves of Agalia odorata (Aod). Stem bark extract of Ae demonstrated the highest activity with the lowest IC99 (495.5 ng/ml) and the steepest slope 1.1325 (Tasanor, 2007).…”

“…Tasanor (2007) tested in vitro three of the allopathic drugs as control (Metronidazole, Dehydroemetine and Dihydroartiminisin) and seven herbs (leaves, root and stem bark of Agalia eleagnoidae (Ae), leaves from Stemona tuberose (St), stem bark and leaves of Agalia odutis (Ao), and leaves of Agalia odorata (Aod). Stem bark extract of Ae demonstrated the highest activity with the lowest IC99 (495.5 ng/ml) and the steepest slope 1.1325 (Tasanor, 2007). The study showed a better response of all herbal medicines as compared to Metronidazole, tested against E. histolytica.…”

Efficacy of Antiamebic Drugs in a Mouse Model

“…7 These data have spurred the development of novel antiamebic therapies; there have been many recent reports of novel potentially antiamebic compounds produced by de novo synthesis and screening of plant-derived compounds. [15][16][17][18][19][20][21][22] Nitazoxanide is a drug recently approved in the United States for cryptosporidiosis. It has been reported to treat intestinal amebiasis both clinically and microbiologically, 5 but no comparative trials with metronidazole have been performed.…”