Unraveling the potential of Artemisia afra, Artemisia annua and Erigeron bonariensis as Culturally Sound Alternative Therapeutic Approaches Against Malaria: Efficacy, Safety and Mode of Action

The emergence and spread of resistance to antimicrobial agents has
increased the probability of treatment failure in the chemotherapy of
infectious diseases. Of interest is the potential resistance to antimalarial
agents. Resistance has been reported in almost all the major classes of
available malarial drugs. The resistance challenge is further compounded by
the lack of safer transmission blocking agents. This limitation, which is
further aggrevated by factors such as cultural impediments to Western
medicines, has led to the resurgent and increasing use of traditional
remedies, especially Artemisia annua and Artemisia afra, in the context of
malaria, among other ailments.
Although proven to be effective in the management of malaria, the use of
these two medicinal plants face tremendous challenges and has been
controvercially advocated for several reasons including batch-to-batch
variations, seasonal and geographical impacts, post-harvest processing
methods leading to inconsistency in the metabolite contents. These
variations in metabolite composition influence the effectiveness of the
medicinal plant. Additionally, there are contradictory reports regarding the
chemical composition, especially the presence and role of artemisinin in both
plants. This project was conceived to address these problems with its major
aim to standardize, validate, and assess the safety of formulations of
Artemisia spp as potential antimalarial agents to accelerate it elimination in
high-transmission settings.
To achieve the aim of this project, firstly, we explore the phytochemical
diversity of both plants harvested from different geographical regions and
seasons in Cameroon, and the impact of post-harvest handling practices on
the metabolite content through HPTLC, HPLC, and GC. In the second phase,
we isolated antiplasmodial and gametocytocidal molecules from A. afra.
Then we proceeded to the development of a formulation of A. afra and
investigated its efficacy and safety profiles. Additionally, analysis of the
phenolic profile of A. afra and A. annua through HPLC, detected and
quantified artemisinin, and performed comparative HPLC-MS metabolomic
analysis on in vitro P. falciparum trophozoites to elucidate the modes of
action. This objective was achieved thanks to Dr. Lucia Mamede through her
colaboration with Pr. Manuel Llinás (Pennsylvania State University, USA). In addition, Erigeron bonariensis, a medicinal plant with traditional use in
Cameroonian folk medicine and other parts of Africa for the management of
ailments, including malaria was equally investigated for its antiplasmodial,
gametocidal activty and toxity.
The findings show that A. annua and A. afra activity profiles are related to
their surroundings, with different phytochemical compositions seen for each
sample depending on the season and place of origin. High artemisinin
contents was retrieved in samples obtained in the rainy for A. annua with
improved antiplasmodial activity. On the other hand, A. afra samples lacked
the sesquiterpene lactone and equally desmonstrated good antiplasmodial
activity. Also, post-harvest handling affected A. annua and A. afra volatile
and polyphenol profiles, and influenced how effective they were against
malaria parasites. Sun-dry method showed the best profiles of terpenes and
polyphenols for both plants. Furthermore, intriguing dual-stage
antiplasmodial and gametocytocidal capabilities were demonstrated by two
compounds that were isolated from A. afra (IC50 values < 5µg/mL).
Meanwhile, on a hedonic score of 9.0, a formulation of A. afra acquired an
overall acceptance level of 7.2, and proved to be effective and safe.
Ultimately, A. afra induced a distinct metabolic response in the parasite, in
contrast to A. annua, which closely aligned with the parasite response profile
generated by purified artemisinin through the redox mechanism of
glutathion.
Moreso, Erigeron bonariensis showed significant antiplasmodial (IC50 6.02 ±
1.13 μg/mL) and gametocytocidal (IC50 1.863 ± 0.717 μg/mL) activity and
relatively safe of toxicity after an acute and subchronic oral exposure in mice.
Generally, the study contributes to the broader exploration of herbal
medicine as a sustainable and culturally relevant approach to combating
malaria, with potential implications for the development of alternative
antimalarial therapies needed to drive malaria elimination efforts. This study
shows the divergent mode of action and equally demonstrates that when
choosing an Artemisia sample as an antimalarial agent we must take into
consideration the season, origin and method of drying.