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

摘要

> 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 ( P lasmodium 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 _0→∞ ), C _max , and t _1/2 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 spe