Marmesin isolated from Celtis durandii Engl. root bioactive fraction inhibits β-hematin formation and contributes to antiplasmodial activity

Malaria is a leading cause of death in many developing countries, especially in sub-Saharan Africa. Nigeria is endowed with an abundance of medicinal plants, many of which are used to treat malaria. Celtis durandii Engl. is one such plant used as a traditional antimalarial remedy in southeast Nigeria. However, its antiplasmodial potential is poorly explored. The study aimed at identifying the antiplasmodial components of C. durandii root extract through antiplasmodial activity-guided fractionation. Dichloromethane/methanol mixture extract (1:1 v/v) of C. durandii root was prepared and partitioned against water to obtain the organic phase, which was further separated by column chromatography into nine (C1 – C9) fractions. The antiplasmodial activity was evaluated by in vitro screening of the different fractions against drug-sensitive and drug-resistant Plasmodium falciparum strains. Further purification of the active column fractions resulted in a potent anti-Plasmodial compound that was subsequently investigated for its effect on β-hematin formation. Additionally, the isolated compound was characterized and identified as marmesin using mass spectrometry and nuclear magnetic resonance spectroscopy. Celtis durandii root extract exhibited promising antiplasmodial activity {IC50 (μg/ml) 5.92, 6.04, and 6.92} against PfW2mef, PfINDO, and Pf3D7 respectively. Pooled fractions with good antiplasmodial activity {IC50 (μg/ml) Pf3D7: 3.99; PfINDO: 2.24} and selectivity for the parasites (SI: 21) yielded a compound that was fourteen-fold potent in antiplasmodial activity against Pf3D7(IC50: 0.28 μg/ml). It also inhibited β-hematin formation with an IC50 = 150 μM. Further studies using spectral data, literature, and chemical databases identified the purified compound as marmesin. This work has demonstrated that Celtis durandii root extract has good antiplasmodial activity against drug-sensitive and drug-resistant P. falciparum. The inhibition of β-hematin formation by marmesin accounts in part for this activity. [Display omitted] •An extract of Celtis durandii root inhibited the growth of P. falciparum in culture.•Its fractions inhibited drug-sensitive and resistant parasites and were non-cytotoxic.•Marmesin purified from the active fraction showed good activity (IC50: 0.28 μg/mL).•Marmesin inhibited β-hematin formation but was not as effective as chloroquine.•C. durandii extract contains compounds that act on distinct intra-parasitic targets.