Artemisinin-Based Combination Therapy Synergized with Medicinal Plants to Induce Musculotoxic Effects

Abstract

Introduction. Multivisceral, neurological, hepatic, and renal damage has been witnessed following the use of artemisinin-based combination therapy (ACT) and herbal medicine. These multiple organ damages make us think of muscle damage. The objective was to study the myotoxicity of the combination of ACTs with medicinal plants. Materials and Methods. Muscle cells (RD cells) were brought into contact with preparations of antimalarial drugs and/or antimalarial herbs. The following drugs were used: artesunate 100 mg/amodiaquine 270 mg (ASAQ) and artemether 80 mg/lumefantrine 480 mg (AL); plant Sida acuta (PSA) and plant Enantia polycarpa (PEP) at 10 µg/ml. After 5 days of incubation, the cells were counted by using a hemocytometer with trypan blue solution. Results. Artesunate/amodiaquine caused a significant drop in the number of muscle cells, compared to the control, between D2 and D4 ( $p$  < 0.001). There was also a significant difference between the control and artemether/lumefantrine between D2 ( $p$  < 0.01) and D4 ( $p$  < 0.001) and between the control and the Sida acuta plant, on D2 ( $p$  < 0.001), D4 ( $p$  < 0.001), and D5 ( $p$  < 0.05). In tubes treated with ASAQ and Sida acuta, cell mortality was over 30%. Finally, statistically significant cell destruction in the tubes treated with the combination of antimalarial drugs and traditional plants compared to those of the control was observed from D2 ( $p$  < 0.001). Conclusion. Artemisinin-based combination therapy remains effective and well tolerated. But its combination with medicinal plants induced myotoxic effects. This toxicity would appear to be of the additive type. Further studies should be able to better elucidate the mechanism of this toxicity.