title: Bioassay-guided fractionation of extracts from Codiaeum variegatum against Entamoeba histolytica discovers compounds that modify expression of ceramide biosynthesis related genes.
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.
authors.affiliation: University of Yaoundé I, Faculty of Science, Department of Biochemistry, Laboratory of Pharmacology and Toxicology, Yaoundé, Cameroon ; Institut Pasteur, Cell Biology of Parasitism Unit, Paris, France ; INSERM U786, Paris, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Mfotie Njoya
authors.affiliation: Institut Pasteur, Cell Biology of Parasitism Unit, Paris, France ; INSERM U786, Paris, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.affiliation: Institut Pasteur, Cell Biology of Parasitism Unit, Paris, France ; INSERM U786, Paris, France.
authors.forename: Nora Adriana
authors.initials: NA
authors.lastname: Hernandez-Cuevas
authors.affiliation: Institut Pasteur, Cell Biology of Parasitism Unit, Paris, France ; INSERM U786, Paris, France.
authors.forename: Chung-Chau
authors.initials: CC
authors.lastname: Hon
authors.affiliation: Institut Pasteur, Unité de Chimie et Biocatalyse, Paris, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Janin
authors.affiliation: University of Yaoundé I, Faculty of Science, Department of Biochemistry, Laboratory of Pharmacology and Toxicology, Yaoundé, Cameroon.
authors.forename: Melanie F G
authors.initials: MF
authors.lastname: Kamini
authors.affiliation: University of Yaoundé I, Faculty of Science, Department of Biochemistry, Laboratory of Pharmacology and Toxicology, Yaoundé, Cameroon.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Moundipa
authors.affiliation: Institut Pasteur, Cell Biology of Parasitism Unit, Paris, France ; INSERM U786, Paris, France.
authors.forename: Nancy
authors.initials: N
authors.lastname: Guillén
mesh_terms: D000981:Antiprotozoal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis; D001681:Biological Assay; D053898:Biosynthetic Pathways / Q000187:drug effects*; D002163:Cameroon; D002470:Cell Survival / Q000187:drug effects; D002518:Ceramides / Q000096:biosynthesis*; D004748:Entamoeba histolytica / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D019665:Euphorbiaceae / Q000737:chemistry*; D006801:Humans; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry
chemical_list: D000981:Antiprotozoal Agents; D002518:Ceramides; D010936:Plant Extracts