Dual assessment of cepharanthine: In vitro and in vivo inhibitory effects on multi-host haemoprotozoa, Trypanosoma evansi.

Cepharanthine, a bioactive alkaloid dervived from the plant Stephania cephalantha has recently gained significant attention for its promising therapeutic potential. In view of the increasing resistance and toxicity reports associated with current treatments for Trypanosoma evansi, the present study evaluated the anti-trypanosomal activity of different concentrations of Cepharanthine against T. evansi under both in vitro and in vivo conditions. Cepharanthine exhibited significant anti-trypanosomal activity, with an IC50 value of 1131 nM at 24 h. Additionally, high specific selectivity indices (SSI) of 78.84 on Vero cell line and 107.78 on equine PBMCs, indicates high safety profile. In the mice model, Cepharanthine cleared parasitemia within 10 days and extended survival period of infected mice by more than 30 days when administered at a dose of 12.5 mg/kg body weight, followed by additional dosages at 48- and 72-hour intervals. In transcript analysis, the upregulated mRNA expression of trypanothione reductase (2.15- fold, p < 0.05) and aurora kinase (1.27-folds, p < 0.05) suggested the disturbance in redox homeostasis and cell cycle regulation by Cepharanthine. On the other hand, trans-sialidase, oligopeptidase, arginine kinase, topoisomerase II, calcium ATPase 1 and ornithine decarboxylase remained unaffected after 24 h of exposure. Collectively, these findings indicate that Cepharanthine exert potent anti-T. evansi activity and may serve as safer alternative to existing conventional anti-trypanosomal drugs against T. evansi.