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, antiinflammatory 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 ¼ 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 EIC 50 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.

Entamoeba histolytica is a parasitic protist which causes amoebiasis in humans. Amoebiasis causes about 100,000 deaths every year worldwide. Currently, the antibiotic, metronidazole is the only effective treatment for amoebiasis. Metronidazole is effective; however, it has a high toxicity and causes damage to the nervous system. Finding an alternative treatment is necessary to manage the disease better and reduce the risks associated with the current medication. In previous studies, purified plant extracts and homologous commercial derivatives have shown significant antimicrobial character. Previously, we identified pomegranate, rhubarb (rhein), and maple syrup (maplifa) extracts as potential inhibitors of E. histolytica trophozoite growth. The effectiveness of the extracts was assessed by growth inhibition assays monitored at 12, 24, and 48 hours using 60 μM or 120 μM concentrations of pure compounds. Rhein and maplifa, showed promising inhibitory activity on E. histolytica trophozoite growth. Testing of compounds of analogous structures is currently in progress. Future studies will be completed to determine the biochemical mechanism of action of each of these inhibitors and test their toxicity to mammalian tissue cultures in comparison to the current drug of choice, metronidazole.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.