“Because current amebiasis drugs are toxic to patients, generate resistance in the pathogen, or can potentially induce cancer, alternative anti-amebic compounds need to be discovered and tested to treat and manage amebiasis. Our study suggests that anthraquinones might be such alternative compounds.”

Our latest publication on amebas is now available open access (links below). Although our research program focuses on taxa, clone and kin discrimination/recognition in unicellular eukaryotes (protists), occasionally we conduct experiments on applied, related topics. Readers might find this post specialized, which is true; we will continue posting about broad(er) themes for all audiences. For now, try to follow the abstract of the scientific article and a simple figure that explains the experiments:

Entamoeba histolytica infects 50 million people worldwide and causes 55 thousand fatalities every year. Current anti-amebic drugs (e.g. paromomycin) work either at the level of the intestinal lumen (where trophozoites proliferate via cell divisions) or on the invasive trophozoites that have penetrated the gut or colonized internal organs (e.g. metronidazole). Some of these drugs are highly toxic to patients, have generated trophozoite resistance, or caused mutations and cancer in laboratory animals. Thus, alternative anti-amebic compounds need to be identified to minimize the side effects (on patients) or resistance (by amebas) to current treatments. The literature suggests that anthraquinones (chemicals found in medicinal plants) have antibacterial, antiparasitic, anti-inflammatory and antioxidant properties. Here we provide experimental evidence that Chinese rhubarb (Rheum palmatum) leaves’ extract (rich in the anthraquinone rhein) inhibits E. histolytica trophozoite growth in vitro. In addition, from a set of ten isolated/synthetic anthraquinones (which we suspected to have anti-amebic properties), four analogs (rhein; AHHDAC = 1-amino-4-hydroxy-9, 10-dioxo-9, 10-dihydro-anthracene-2-carboxylic acid; unisol blue AS; and sennoside B) efficiently inhibited amebic growth at EIC₅₀ concentrations comparable to metronidazole. The mechanism of action of these compounds still needs to be determined, although anthraquinones might enhance the production of toxic oxygen metabolites as it has been suggested for various protists (e.g. Leishmania, Plasmodium, Trypanosoma). Our research is the first to explore anti-amebic effects of Chinese rhubarb leaves’ extract and isolated/synthetic anthraquinones on pathogenic Entamoeba.

Above (click on image to enlarge) – Experimental design: tests with Chinese rhubarb (Rheum palmatum) extract (“rhein extract”) or with isolated/synthetic anthraquinones. Top: Extract obtained from Chinese rhubarb leaves was added to suspensions of Entamoeba histolytica trophozoites and incubated for 24h or 48 h at 37 °C; likewise, metronidazole (20 μM), TYI-S-33 media or TYI-S-33 media + DMSO (dimethyl sulfoxide) were added to separate suspensions (both controls); each series was done in triplicate (x3, total 24 wells). Bottom: From commercially available isolated/synthetic anthraquinones (rationale in Methods), four analogs (rhein; AHDDAC = 1-amino-4-hydroxy-9, 10-dioxo-9, 10-dihydro-anthracene-2-carboxylic acid; unisol blue AS; or sennoside B) were added (concentrations 60 μM or 120 μM) to the suspensions of trophozoites and incubated for 24h or 48 h at 37 °C; metronidazole, TYI-S-33 media or TYI-S-33 media + DMSO were separately added as in above; each series was done in triplicate (x3, total 84 wells).

The open access files are available at Helion, PDF, and NCBI PubMed.

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