Combination of artemisinin‐based natural compounds from Artemisia annua L. for the treatment of malaria: Pharmacodynamic and pharmacokinetic studies

Abstract

Currently, the most effective antimalarial is artemisinin, which is extracted from the leaves of medicinal herb Artemisia annua L. (A. annua). Previous studies showed that the complex chemical matrix of A. annua could enhance both the bioavailability and efficacy of artemisinin. The present study aims to evaluate the efficacy and pharmacokinetic properties of a combination therapy based on artemisinin and 3 components from A. annua with high content (arteannuin B, arteannuic acid, and scopoletin). In vivo antimalarial activity was assessed following a 4-day treatment in murine malaria models (Plasmodium yoelii and Plasmodium berghei). Results showed that a much sharper reduction in parasitemia (~93%) was found in combination therapy compared with pure artemisinin (~31%), indicating pharmacodynamic synergism occurring between artemisinin and arteannuin B, arteannuic acid, and scopoletin. Multiple-dose pharmacokinetics further demonstrated that combination therapy results in increased area under the curve (AUC ), C , and t by 3.78-, 3.47-, and 1.13-fold in healthy mice, respectively, and by 2.62-, 1.82-, and 1.22-fold in P. yoelii-infected mice, respectively. The calculated oral clearance of combination therapy in healthy and P. yoelii-infected mice was also reduced. These findings imply that specific components in A. annua might offer a possibility to develop new artemisinin-based natural combination therapy for malaria treatment.

RETRACTED: Artemisia annua and Artemisia afra tea infusions vs. artesunate-amodiaquine (ASAQ) in treating Plasmodium falciparum malaria in a large scale, double blind, randomized clinical trial

“…artesunate, A. annua (DLA) eliminated parasites within a few days even in comatose pediatrics (Daddy et al, 2017). Studies showed that the numerous phytochemicals in A. annua and A. afra provide synergies and multiple interactions, likely constituting a polytherapy against malaria (Elford et al, 1987;Li et al, 2018;Liu et al, 1992;Suberu et al, 2013). Together, those data and this study indicate that artemisinin is not the sole phytochemical demonstrating antimalarial efficacy by Artemisia sp.…”

An overview of the anti-SARS-CoV-2 properties of Artemisia annua, its antiviral action, protein-associated mechanisms, and repurposing for COVID-19 treatment

“…The transfer of knowledge from academic research to clinical use can take many years. Given the urgency of the current pandemic, the existence of previous pharmacokinetic, pharmacodynamic, and cytotoxicity studies of A. annua and its compounds are additional factors that make them interesting candidates for drug repurposing [23] , [24] , [25] . Thus, due to the multifunctional properties of A. annua and artemisinins against different viruses and their strong safety profiles, their applicability as an anti-SARS-CoV-2 seems promising and should be further investigated.…”

Simultaneous Quantification of Five Sesquiterpene Components after Ultrasound Extraction in Artemisia annua L. by an Accurate and Rapid UPLC–PDA Assay

“…In recent years, more and more researchers—including our team—have paid attention to the therapeutic activities of A. annua multi-components in the treatment of malaria [22]. A recent study found that the combination of Art B, AA, scopoletin and Art could improve the efficacy of Art [23,24,25]. Therefore, sesquiterpenoids are the most specific compounds for the treatment of malaria.…”