In vitro antiplasmodial activity-directed investigation and UPLC-MS fingerprint of promising extracts and fractions from Terminalia ivorensis A. Chev. and Terminalia brownii Fresen

Mariscal Brice Tchatat Tali; Darline Dize; Steven Collins Njonte Wouamba; Patrick Valere Tsouh Fokou; Rodrigue Keumoe; Cyrille Njanpa Ngansop; Michelle Sidoine Nguembou Njionhou; Cedric Derick Jiatsa Mbouna; Lauve Rachel Yamthe Tchokouaha; Vinesh Maharaj; Ndivhuwo Kevin Khorommbi; Dashnie Naidoo-Maharaj; Jean Claude Tchouankeu; Fabrice Fekam Boyom

doi:10.1016/j.jep.2022.115512

In vitro antiplasmodial activity-directed investigation and UPLC-MS fingerprint of promising extracts and fractions from Terminalia ivorensis A. Chev. and Terminalia brownii Fresen

J Ethnopharmacol. 2022 Oct 5:296:115512. doi: 10.1016/j.jep.2022.115512. Epub 2022 Jul 1.

Authors

Mariscal Brice Tchatat Tali¹, Darline Dize², Steven Collins Njonte Wouamba³, Patrick Valere Tsouh Fokou⁴, Rodrigue Keumoe⁵, Cyrille Njanpa Ngansop⁶, Michelle Sidoine Nguembou Njionhou⁷, Cedric Derick Jiatsa Mbouna⁸, Lauve Rachel Yamthe Tchokouaha⁹, Vinesh Maharaj¹⁰, Ndivhuwo Kevin Khorommbi¹¹, Dashnie Naidoo-Maharaj¹², Jean Claude Tchouankeu¹³, Fabrice Fekam Boyom¹⁴

Affiliations

¹ Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon. Electronic address: b.tchatat@yahoo.com.
² Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon. Electronic address: darline.dize@yahoo.fr.
³ Laboratory of Natural Products and Organic Synthesis, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon; Department of Chemistry, Higher Teacher's Training College, University of Yaoundé I, P. O. Box 47, Yaoundé, Cameroon. Electronic address: wouamba01s@yahoo.fr.
⁴ Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon; Department of Biochemistry, Faculty of Science, University of Bamenda, PO Box 39, Bambili, Bamenda, Cameroon. Electronic address: ptsouh@gmail.com.
⁵ Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon. Electronic address: rkeumoe@yahoo.fr.
⁶ Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon. Electronic address: njampacyrille2@yahoo.com.
⁷ Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon. Electronic address: m.nguembou@yahoo.fr.
⁸ Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon. Electronic address: cedrickjiatsa@yahoo.com.
⁹ Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon; Institute for Medical Research and Medicinal Plants Studies (IMPM), Yaoundé, P.O. Box 6163, Yaoundé, Cameroon. Electronic address: yamthe_lauve@yahoo.fr.
¹⁰ Department of Chemistry, University of Pretoria, Hatfield Campus, Hatfield, 0028, South Africa. Electronic address: vinesh.maharaj@up.ac.za.
¹¹ Department of Chemistry, University of Pretoria, Hatfield Campus, Hatfield, 0028, South Africa. Electronic address: khorombink@gmail.com.
¹² Department of Chemistry, University of Pretoria, Hatfield Campus, Hatfield, 0028, South Africa; Agricultural Research Council-Vegetables, Industrial and Medicinal Plants, Private Bag X293, Pretoria, 0001, South Africa. Electronic address: dashnienaidoo@gmail.com.
¹³ Laboratory of Natural Products and Organic Synthesis, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon. Electronic address: jctchouank@yahoo.com.
¹⁴ Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon. Electronic address: fabrice.boyom@fulbrightmail.org.

PMID: 35788037
DOI: 10.1016/j.jep.2022.115512

Abstract

Ethnopharmacological significance: Medicinal plants from the Terminalia genus are widely used as remedies against many infectious diseases, including malaria. As such, Terminalia ivorensis A. Chev. and Terminalia brownii Fresen. are famous due to their usefulness in traditional medicines to treat malaria and yellow fever. However, further information is needed on the extent of anti-Plasmodium potency of extracts and fractions from these plants and their phytochemical profile.

Aim of the study: This study was designed to investigate the in vitro antiplasmodial activity and to determine the chemical profile of promising extracts and fractions from T. ivorensis and T. brownii stem bark.

Materials and methods: Crude aqueous, ethanolic, methanolic, hydroethanolic and ethyl acetate extracts were prepared by maceration from the stem barks of T. brownii and T. ivorensis. They were subsequently tested against chloroquine-sensitive (Pf3D7) and multidrug-resistant (PfDd2) strains of P. falciparum using the parasite lactate dehydrogenase (PfLDH) assay. Extracts showing very good activity on both plasmodial strains were further fractionated using column chromatography guided by evidence of antiplasmodial activity. All bioactive extracts and fractions were screened for their cytotoxicity on Vero and Raw cell lines using the resazurin-based assay and on erythrocytes using the hemolysis assay. The phytochemical profiles of selected potent extracts and fractions were determined by UPLC-QTOF-MS analysis.

Results: Of the ten extracts obtained from both plant species, nine showed inhibitory activity against both P. falciparum strains (Pf3D7 and PfDd2), with median inhibitory concentration (IC₅₀) values ranging from 0.13 μg/ml to 10.59 μg/ml. Interestingly, the aqueous extract of T. ivorensis (Ti^W) and methanolic extract of T. brownii (Tb^M) displayed higher antiplasmodial activities against both strains (IC₅₀ 0.13-1.43 μg/ml) and high selectivity indices (SI > 100). Their fractionation led to two fractions from T. ivorensis and two from T. brownii that showed very promising antiplasmodial activity (IC₅₀ 0.15-1.73 μg/mL) and SI greater than 100. The hemolytic assay confirmed the safety of crude extracts and fractions on erythrocytes. UPLC-MS-based phytochemical analysis of the crude aqueous extract of T. ivorensis showed the presence of ellagic acid (1) and leucodelphidin (2), while analysis of the crude methanol extract of T. brownii showed the presence of ellagic acid (1), leucodelphinidin (2), papyriogenin D (3), dihydroactinidiolide (4) and miltiodiol (5).

Conclusions: The extracts and fractions from T. ivorensis and T. brownii showed very good antiplasmodial activity, thus supporting the traditional use of the two plants in the treatment of malaria. Chemical profiling of the extracts and fractions led to the identification of chemical markers and the known antimalarial compound ellagic acid. Further isolation and testing of other pure compounds from the active fractions could lead to the identification of potent antiplasmodial compounds.

Keywords: Antiplasmodial; Fractionation; Plasmodium falciparum; Terminalia brownii; Terminalia ivorensis; UPLC–MS fingerprints.

MeSH terms

Antimalarials*
Chromatography, High Pressure Liquid
Chromatography, Liquid
Ellagic Acid / therapeutic use
Humans
Malaria* / drug therapy
Malaria, Falciparum* / drug therapy
Phytochemicals / therapeutic use
Plant Extracts
Plasmodium falciparum
Plasmodium*
Tandem Mass Spectrometry
Terminalia* / chemistry

Substances

Antimalarials
Phytochemicals
Plant Extracts
Ellagic Acid