AUTHOR=Schultz Fabien , Osuji Ogechi Favour , Nguyen Anh , Anywar Godwin , Scheel John R. , Caljon Guy , Pieters Luc , Garbe Leif-Alexander 

TITLE=Pharmacological Assessment of the Antiprotozoal Activity, Cytotoxicity and Genotoxicity of Medicinal Plants Used in the Treatment of Malaria in the Greater Mpigi Region in Uganda

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.678535

DOI=10.3389/fphar.2021.678535

ISSN=1663-9812

ABSTRACT=<p>We investigated the potential antimalarial and toxicological effects of 16 medicinal plants frequently used by traditional healers to treat malaria, fever, and related disorders in the Greater Mpigi region in Uganda. Species studied were <italic>Albizia coriaria</italic>, <italic>Cassine buchananii</italic>, <italic>Combretum molle</italic>, <italic>Erythrina abyssinica</italic>, <italic>Ficus saussureana</italic>, <italic>Harungana madagascariensis</italic>, <italic>Leucas calostachys</italic>, <italic>Microgramma lycopodioides</italic>, <italic>Morella kandtiana</italic>, <italic>Plectranthus hadiensis</italic>, <italic>Securidaca longipedunculata</italic>, <italic>Sesamum calycinum subsp. angustifolium</italic>, <italic>Solanum aculeastrum</italic>, <italic>Toddalia asiatica</italic>, <italic>Warburgia ugandensis,</italic> and <italic>Zanthoxylum chalybeum</italic>. In addition, the traditional healers indicated that <italic>P. hadiensis</italic> is used as a ritual plant to boost fertility and prepare young women and teenagers for motherhood in some Ugandan communities where a high incidence of rapidly growing large breast masses in young female patients was observed (not necessarily breast cancer). We present results from various <italic>in vitro</italic> experiments performed with 56 different plant extracts, namely, 1) an initial assessment of the 16 species regarding their traditional use in the treatment of malaria by identifying promising plant extract candidates using a heme biocrystallization inhibition library screen; 2) follow-up investigations of antiprotozoal effects of the most bioactive crude extracts against chloroquine-resistant <italic>P. falciparum</italic> K1; 3) a cytotoxicity counterscreen against human MRC-5<sub>SV2</sub> lung fibroblasts; 4) a genotoxicity evaluation of the extract library without and with metabolic bioactivation with human S9 liver fraction; and 5) an assessment of the mutagenicity of the ritual plant <italic>P. hadiensis</italic>. A total of seven extracts from five plant species were selected for antiplasmodial follow-up investigations based on their hemozoin formation inhibition activity in the heme biocrystallization assay. Among other extracts, an ethyl acetate extract of <italic>L. calostachys</italic> leaves exhibited antiplasmodial activity against <italic>P. falciparum</italic> K1 (IC<sub>50</sub> value: 5.7 µg/ml), which was further characterized with a selectivity index of 2.6 (CC<sub>50</sub> value: 14.7 µg/ml). The experiments for assessment of potential procarcinogenic properties of plant extracts <italic>via</italic> evaluation of <italic>in vitro</italic> mutagenicity and genotoxicity indicated that few extracts cause mutations. The species <italic>T. asiatica</italic> showed the most significant genotoxic effects on both bacterial test strains (without metabolic bioactivation at a concentration of 500 µg/plate). However, none of the mutagenic extracts from the experiments without metabolic bioactivation retained their genotoxic activity after metabolic bioactivation of the plant extract library through pre-incubation with human S9 liver fraction. While this study did not show that <italic>P. hadiensis</italic> has genotoxic properties, it did provide early stage support for the therapeutic use of the medicinal plants from the Greater Mpigi region.</p>