Investigation of the efficacy of cinnamaldehyde, cannabidiol and, eravacycline in a malaria model

Objective: In this study, it was aimed to investigate the cytotoxic activity, suppression rate and antimalarial activity of cinnamaldehyde and cannabidiol, which have shown strong antimicrobial activities as well as various biological activities, and eravacycline, a new generation derivative of tetracyclines, in an in vivo malaria model. Materials and Methods: The cytotoxic activities of the active substances were determined by the MTT method against L929 mouse fibroblasts, and their antimalarial activity by the 4-day test in an in vivo mouse model. In this study, five groups were formed: the cinnamaldehyde group (CIN), the cannabidiol group (CBD), the eravacycline group (ERA), the chloroquine group (KG) and the untreated group (TAG). 2.5 x 107 parasites/ml of P. berghei-infected erythrocyte suspension was administered IP to all mice. The determined doses of active substances were given to the mice by oral gavage in accordance with the 4-day test, and the parasitemia status in the mice was controlled for 21 days with smear preparations made from the blood taken from the tail end of the mice. Results: The IC50 values, which express the cytotoxic activity values of the active substances were determined as 27,75 μg/ml, 16.40 μM and 48,82 μg/ml for CIN, CBD and ERA, respectively. The mean parasitemia rate in untreated mice was 33% on day 9 and all mice died on day 11. On the ninth day, when compared with the TAG group, no parasites were observed in the CIN group, while the average parasitemia was 0,08% in the CBD group and 17,8% in the ERA group. Compared to the mice in the TAG group, the life expectancy of the other groups was prolonged by 8 days in the CIN group, 12 days in the CBD group, and 8 days in the ERA group. Conclusion: It has been determined that all three active subtances tested in this study suppress the development of Plasmodium parasites in an in vivo mouse model and prolong the life span of the mice. It is thougth that the strong antimalarial activity of CIN and CBD shown in the study and the possible positive effect of ERA on the clinical course can be improved by combining existing and potential antimalarial molecules.