Articles
Whole-plant Artemisia annua extract mitigates artemisinin resistance: evidence for synergistic phytochemical effects against chloroquine-resistant Plasmodium falciparum
Article number
1462_19
Pages
125 – 132
Language
English
Abstract
Artemisinin resistance in Plasmodium falciparum represents a critical global health security threat, particularly with first-line artemisinin combination therapies (ACTs) becoming essential for malaria control.
Emerging resistance in Southeast Asia and the risk of African spread threaten malaria elimination strategies.
Previous studies suggest whole-plant Artemisia annua preparations may slow resistance development compared to pure artemisinin, but mechanisms remain unclear.
This study compared resistance emergence following cyclic in vitro exposures of chloroquine-resistant P. falciparum (W2 strain) to either pure artemisinin or phytochemically complex A. annua leaf extract.
Parasites exposed to 40 cycles of pure artemisinin (IC50 equivalent) showed consistent incremental increases in IC50 values, indicating progressive resistance development (relative sensitivity index, RSI, increasing significantly with cycles). In contrast, parasites exposed to equivalent IC50 doses of A. annua extract showed no comparable increases in IC50 values across 40 cycles, demonstrating resistance-mitigating effects.
The extract contains 0.74±0.06% artemisinin plus synergistic flavonoids, sesquiterpenes, and monoterpenes.
Results demonstrate that whole-plant A. annua phytochemical complexity confers resistance-mitigating effects, likely through multiple compound interactions forestalling single-pathway resistance mechanisms.
These findings support ethnopharmacological use of A. annua extracts over pure artemisinin for malaria treatment, with implications for preservation of ACT efficacy, cost-effectiveness of locally-cultivable preparations, and economic benefits for malaria-endemic regions.
Emerging resistance in Southeast Asia and the risk of African spread threaten malaria elimination strategies.
Previous studies suggest whole-plant Artemisia annua preparations may slow resistance development compared to pure artemisinin, but mechanisms remain unclear.
This study compared resistance emergence following cyclic in vitro exposures of chloroquine-resistant P. falciparum (W2 strain) to either pure artemisinin or phytochemically complex A. annua leaf extract.
Parasites exposed to 40 cycles of pure artemisinin (IC50 equivalent) showed consistent incremental increases in IC50 values, indicating progressive resistance development (relative sensitivity index, RSI, increasing significantly with cycles). In contrast, parasites exposed to equivalent IC50 doses of A. annua extract showed no comparable increases in IC50 values across 40 cycles, demonstrating resistance-mitigating effects.
The extract contains 0.74±0.06% artemisinin plus synergistic flavonoids, sesquiterpenes, and monoterpenes.
Results demonstrate that whole-plant A. annua phytochemical complexity confers resistance-mitigating effects, likely through multiple compound interactions forestalling single-pathway resistance mechanisms.
These findings support ethnopharmacological use of A. annua extracts over pure artemisinin for malaria treatment, with implications for preservation of ACT efficacy, cost-effectiveness of locally-cultivable preparations, and economic benefits for malaria-endemic regions.
Publication
Authors
L.N. Kangethe, H. Hassanali, J. Nganga, J. Kinyua, S. Omar, F. Kimani
Keywords
Artemisia annua, artemisinin resistance, phytochemical synergy, Plasmodium falciparum, whole-plant extract, resistance mitigation, ethnopharmacology
Online Articles (28)