• Anneke du Toit and Frank van der Kooy.
• Unit for Drug Research and Development, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa. Electronic address: annekedutoit00@gmail.com.
• J Ethnopharmacol. 2019 Nov 15; 244: 112127.

Ethnoparmacological RelevanceArtemisia afra is one of the most widely used herbal remedies in South Africa. This highly aromatic shrub is used to treat various disorders including coughs, colds, influenza, and malaria. Due to the long tradition of use and popularity of A. afra, it has been successfully commercialised and can currently be bought from various internet stores and pharmacies. The most notable indication is for the prophylaxis and treatment of Plasmodium falciparum infections. In 2013, the Medicine Control Council (MCC) of South Africa banned the sale of A. afra for the treatment of malaria because it lacks scientific evidence of efficacy. This resulted in a lawsuit being filed in 2017 against the MCC by an herbal company which claimed that artemisinin was responsible for A. afra's antiplasmodial activity. At the time, no scientific literature reported that A. afra contained artemisinin.Materials And MethodsThis review aims to collate all available scientific literature regarding the phytochemistry and biological activity, focusing on antimalarial activity, of A. afra published from 2009 to 2019 and follows on our earlier review, which covered all literature until 2009. All scientific literature in English published between 2009 and June 2019 were retrieved from scientific databases (Scifinder scholar, Web of Science, Scopus, PubMed, Google scholar) and a number of books regarding medicinal plants in South Africa were also consulted.ResultsIn the last decade very few compounds have been identified in A. afra, none of which were novel compounds. Based on all the tests that have been conducted using extracts and compounds of A. afra in a disparate variety of in vitro and in vivo bioassays, the results indicate only weak biological activity. The activity of extracts, and in some cases pure compounds, exhibited IC50 or MIC values of 1000-10 000 fold less active than the positive controls. In contrast, and quite surprisingly, two randomised controlled trials were recently conducted (Schistosoma mansoni and Plasmodium falciparum infected patients) and although criticised based on design, execution, statistical analysis and ethical concerns, showed remarkably positive results.ConclusionsPre-clinical in vitro and in vivo animal experiments failed to yield any promising drug leads. However, if the recent randomised controlled trials can be independently replicated in well-designed and executed clinical trials it might indicate that A. afra contain powerful 'prodrugs'. Future research on A. afra should therefore focus on reproducing the randomised controlled trials and on artificially metabolising A. afra extracts/compounds in order to identify the presence of any 'prodrugs'.Copyright © 2019 Elsevier B.V. All rights reserved.

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