Abstract
Leaves of Codiaeum variegatum (“garden croton”) are used against bloody diarrhoea by local populations in Cameroon. This study aims to search for the active components from C. variegatum against Entamoeba histolytica, and thereby initiate the study of their mechanism of action. A bioassay-guided screening of the aqueous extracts from C. variegatum leaves and various fractions was carried out against trophozoites of E. histolytica axenic culture. We found that the anti-amoebic activity of extracts changed with respect to the collection criteria of leaves. Thereby, optimal conditions were defined for leaves' collection to maximise the anti-amoebic activity of the extracts. A fractionation process was performed, and we identified several sub-fractions (or isolated compounds) with significantly higher anti-amoebic activity compared to the unfractionated aqueous extract. Anti-amoebic activity of the most potent fraction was confirmed with the morphological characteristics of induced death in trophozoites, including cell rounding and lysis. Differential gene expression analysis using high-throughput RNA sequencing implies the potential mechanism of its anti-amoebic activity by targeting ceramide, a bioactive lipid involved in disturbance of biochemical processes within the cell membrane including differentiation, proliferation, cell growth arrest and apoptosis. Regulation of ceramide biosynthesis pathway as a target for anti-amoebic compounds is a novel finding which could be an alternative for drug development against E. histolytica.
Highlights
Medicinal plants are recognized by the World Health Organization as alternatives in the treatment of various diseases and the interest of health professionals for medicinal plants is increasing everyday [1]
In vitro anti-amoebic activity of extracts The anti-amoebic action of C. variegatum was assessed on axenic culture of trophozoites and the results are presented as follow: in the presence of the plant aqueous extract, the growth inhibition or mortality of E. histolytica increases in a concentration dependent manner and the collection criteria of leaves for extract preparation as well as the period of incubation significantly influenced the mortality rate
We hypothesize that the active components within SF9B might act through destabilization of cell architecture caused by changes in levels of ceramide, a membrane lipid involved in apoptosis and cell growth inhibition
Summary
Medicinal plants are recognized by the World Health Organization as alternatives in the treatment of various diseases and the interest of health professionals for medicinal plants is increasing everyday [1]. Medicinal plants contain a variety of secondary metabolites, which can be used to prevent or cure diseases, or to promote general health and well-being [2],[3]. It is estimated that natural products and their derivatives and analogues represent over 50% of all drugs in clinical use [5],[6]. In Cameroon, biodiversity is an important source of bioactive natural compounds and exploration of this biodiversity, based on ethnopharmacology approach from traditional healers, represents a promising strategy to fight against diseases such as intestinal infections. We have focused on amoebiasis, a human infectious disease caused by the amoebic parasite Entamoeba histolytica, which mainly targets intestine and liver. Humans are the only relevant host of this parasite and infection occurs upon ingestion of contaminated water or food containing cysts forms of E. histolytica. Amoebic liver abscesses are the most frequent with severe extra-intestinal clinical manifestations of Author Summary
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