The In Vitro Antimalarial, Toxicological and Chemical Characteristics of Select Phytomedicines and Major Constituents

Abstract

Plants are an important part of medicine in treating both communicable and non-communicable diseases. As the prevalence and spread of drug-resistant malaria has increased, so too has the search for new compounds to treat this lethal disease. Phytomedicines are popular alternatives to allopathic medicine in Africa, making them promising candidates in this search. Based on their known toxicological and chemical characteristics, there is a need to investigate the extent to which the crude extracts of the plants Camelia sinensis, Viscum album, Siphonochilus aethiopicus, and Warburgia salutaris, and their predicted constituents, inhibit chloroquine (CQ)- sensitive and -resistant strains of P. falciparum. Aqueous (70 C, MilliQ® water) and organic (dichloromethane:methanol - 1:1; acetone) crude extracts were prepared from commercially sourced C. sinensis, V. album, S. aethiopicus, and W. salutaris material. Qualitative tests were performed on each crude extract to determine the presence of alkaloids, flavonoids, anthraquinones, coumarins, phenols, saponins, and tannins, followed by quantitative HPLC fingerprinting and total flavonoid and phenolic content assays. Antiplasmodial activity of the crude extracts and major constituents were assessed against CQ-sensitive (NF54) and CQ-resistant (FCR-3) P. falciparum strains. Preliminary toxicology of the crude extracts and their major constituents were profiled based on their ability to induce haemolysis and cytotoxicity in K562 and HepG2 cells. Cuprous and ferrous chelation and free radical scavenging assays were undertaken to consider possible mechanisms of action of the crude extracts regarding any antiplasmodial activity. In silico predictions provided information on the pharmacokinetic characteristics of major constituents. Crude extract % yields ranged from the lowest yield of 3.43% (V. album DCM:MeOH) to 33.99% (C. sinensis aqueous). The crude acetone extract and the major constituent, S. aethiopicus acetone and ellagic acid, had the greatest antiplasmodial activity on both strains. Phenols and tannins were most abundant while anthraquinones and coumarins were absent in all extracts. The DCM:MeOH extract of C. sinensis appeared to have the highest amounts of secondary metabolites, while the aqueous extract of S. aethiopicus had the least comparatively. All extracts and major constituents induced minimal haemolysis (1-3%) and cytotoxicity (<60%), except for polygodial and the S. aethiopicus crude extract. None of the crude extracts had favourable cuprous or ferrous chelating properties (>60%) at 100 μg/mL, while only the C. sinensis DCM:MeOH extract (IC50 = 9.97 ± 0.17 μg/mL) had free radical scavenging properties (>95%) comparable to the standard, ascorbic acid. S. aethiopicus organic extracts and ellagic acid have good activity antiplasmodial activity and could interact in an additive manner with standard antimalarials. Thereby further investigation into their chemical and toxicological profile, as well as the mechanism of their antiplasmodial activity is warranted.