Extracts Obtained from Pterocarpus angolensis DC and Ziziphus mucronata Exhibit Antiplasmodial Activity and Inhibit Heat Shock Protein 70 (Hsp70) Function

Abstract

Malaria parasites are increasingly becoming resistant to currently used antimalarial therapies, therefore there is an urgent need to expand the arsenal of alternative antimalarial drugs. In addition, it is also important to identify novel antimalarial drug targets. In the current study, extracts of two plants, Pterocarpus angolensis and Ziziphus mucronata were obtained and their antimalarial functions were investigated. Furthermore, we explored the capability of the extracts to inhibit Plasmodium falciparum heat shock protein 70 (Hsp70) function. Heat shock protein 70 (Hsp70) are molecular chaperones whose function is to facilitate protein folding. Plasmodium falciparum the main agent of malaria, expresses two cytosol-localized Hsp70s: PfHsp70-1 and PfHsp70-z. The PfHsp70-z has been reported to be essential for parasite survival, while inhibition of PfHsp70-1 function leads to parasite death. Hence both PfHsp70-1 and PfHsp70-z are potential antimalarial drug targets. Extracts of P. angolensis and Z. mucronata inhibited the basal ATPase and chaperone functions of the two parasite Hsp70s. Furthermore, fractions of P. angolensis and Z. mucronata inhibited P. falciparum 3D7 parasite growth in vitro. The extracts obtained in the current study exhibited antiplasmodial activity as they killed P. falciparum parasites maintained in vitro. In addition, the findings further suggest that some of the compounds in P. angolensis and Z. mucronata may target parasite Hsp70 function.

Julbernardia paniculata and Pterocarpus angolensis: From Ethnobotanical Surveys to Phytochemical Characterization and Bioactivities Evaluation

“…Tables 2 and 3 resume the analysis of the phenolic compounds for both plants. It was verified that gallic acid is not abundantly present in the crude extracts and fractions of J. paniculata and P. angolensis, as it was also previously reported for P. angolensis extracts [19]. Similar results were observed for caffeic acid and taxifolin [19].…”

“…It was verified that gallic acid is not abundantly present in the crude extracts and fractions of J. paniculata and P. angolensis, as it was also previously reported for P. angolensis extracts [19]. Similar results were observed for caffeic acid and taxifolin [19]. It is difficult to compare the results now obtained for J. paniculata, since, to the best of our knowledge, this is the first study reporting its phenolic profile.…”

“…Contrariwise to what is verified in P. angolensis, whose leaves generally presented more polyphenols than barks. Previous works reported the presence of these compounds on P. angolensis extracts [12,[17][18][19].…”

“…Furthermore, P. angolensis was reported to exhibit anti-inflammatory activity and high inhibitory activity against Staphylococcus aureus, Escherichia coli and Salmonella Typhimurium [3,18]. It was also demonstrated that extracts of P. angolensis exhibited antiplasmodial activity, suppressing the chaperone activities and ATPase functions of the two parasite cytosol localized chaperones [19].…”

Partners in Mischief: Functional Networks of Heat Shock Proteins of Plasmodium falciparum and Their Influence on Parasite Virulence

“…EGCG exhibited antiplasmodial activity with IC 50 of 2.9 µM, compared to CQ which registered IC 50 of 8.5 nM under similar growth conditions [118]. Interestingly, a plant extract enriched in epicatechin, which is structurally closely related to EGCG, also inhibited P. falciparum Hsp70 and exhibited antiplasmodial action [119]. This suggests that at least some parasite Hsp70s are essential for normal parasite growth, but these studies have not yet found support from reverse genetics, probably due to the hesitation by researchers to attempt to knock out a gene which is highly likely to be essential.…”