Identification of 3,3′-O-dimethylellagic acid and apigenin as the main antiplasmodial constituents of Endodesmia calophylloides Benth and Hymenostegia afzelii (Oliver.) Harms

Abstract

Background Endodesmia calophylloides and Hymenostegia afzelii belong to the Guttiferae and Caesalpiniaceae plant families with known uses in African ethno-medicine to treat malaria and several other diseases. This study aimed at identifying antiplasmodial natural products from selected crude extracts from H. afzelii and E. calophylloides and to assess their cytotoxicity. Methods The extracts from H. afzelii and E. calophylloides were subjected to bioassay-guided fractionation to identify antiplasmodial compounds. The hydroethanol and methanol stem bark crude extracts, fractions and isolated compounds were assessed for antiplasmodial activity against the chloroquine-sensitive 3D7 and multi-drug resistant Dd2 strains of Plasmodium falciparum using the SYBR green I fluorescence-based microdilution assay. Cytotoxicity of active extracts, fractions and compounds was determined on African green monkey normal kidney Vero and murine macrophage Raw 264.7 cell lines using the Resazurin-based viability assay. Results The hydroethanolic extract of H. afzelii stem bark (HasbHE) and the methanolic extract of E. calophylloides stem bark (EcsbM) exhibited the highest potency against both Pf3D7 (EC50 values of 3.32 ± 0.15 μg/mL and 7.40 ± 0.19 μg/mL, respectively) and PfDd2 (EC50 of 3.08 ± 0.21 μg/mL and 7.48 ± 0.07 μg/mL, respectively) strains. Both extracts showed high selectivity toward Plasmodium parasites (SI > 13). The biological activity-guided fractionation led to the identification of five compounds (Compounds 1–5) from HasbHE and one compound (Compound 6) from EcsbM. Of these, Compound 1 corresponding to apigenin (EC50Pf3D7, of 19.01 ± 0.72 μM and EC50PfDd2 of 16.39 ± 0.52 μM), and Compound 6 corresponding to 3,3′-O-dimethylellagic acid (EC50Pf3D7 of 4.27 ± 0.05 μM and EC50PfDd2 of 1.36 ± 0.47 μM) displayed the highest antiplasmodial activities. Interestingly, both compounds exhibited negligible cytotoxicity against both Vero and Raw 264.7 cell lines with selectivity indices greater than 9. Conclusions This study led to the identification of two potent antiplasmodial natural compounds, 3,3′-O-dimethylellagic acid and apigenin that could serve as starting points for further antimalarial drug discovery.

Biological activities and physicochemical characterization of alkaline lignins obtained from branches and leaves of Buchenavia viridiflora with potential pharmaceutical and biomedical applications

“…The results show a decrease in viability with increasing concentration. A similar profile was obtained by Nugraha et al [95] and Keumoe et al [96] evaluating different phenolic compounds against the Plasmodium falciparum strain (Dd2). Through the curves obtained, it was possible to determine the IC 50 (concentration capable of inhibiting the growth of the parasite by 50 %) in ng/mL.…”

Antileishmanial and Antiplasmodial Activities of Secondary Metabolites from the Root of Antrocaryon klaineanum Pierre (Anacardiaceae)

“…3,3′-dimethylellagic acid is a bioactive polyphenolic compound naturally present as a secondary metabolite in many plants. Indeed, a bioassay guided fractionation of Hymenostegia afzelii and Endodesmia calophylloides identified 3,3′-dimethylellagic as the highest antiplasmodial compound with an IC 50s of 4.27 μM and 1.36 μM against Pf 3D7 and Pf Dd2, respectively [ 38 ]. Moreover, ellagic acid exhibited an in vitro effect against Leishmania donovani.…”

Antiviral activity of chrysin and naringenin against porcine epidemic diarrhea virus infection

“…Microplate reader (BioTek, Winooski, VT, United States) was used to measure the 96-well plate at 570 nm, and the cell viability (%) was calculated by OD values ( 23 ). Taking the drug concentration as the abscissa and the percentage of cell viability as the ordinate, the dose-dependent curve of cell viability was drawn by Graphpad 5.0 software and regression was performed to calculate the 50% cytotoxity concentration (CC50) ( 24 ). The percentage of relative cell viability was calculated according to the formula:…”