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

Abstract

Ethnopharmacological relevance: 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.

Aim of the study: The study aimed at identifying the antiplasmodial components of C. durandii root extract through antiplasmodial activity-guided fractionation.

Materials and methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Antiplasmodial; Celtis durandii; Malaria; Marmesin; Plant extract; Plasmodium falciparum.