In vitro and in vivo growth inhibitory activities of cryptolepine hydrate against several Babesia species and Theileria equi

Piroplasmosis treatment has been based on the use of imidocarb dipropionate or diminazene
aceturate (DA), however, their toxic effects. Therefore, the discovery of new drug molecules
and targets is urgently needed. Cryptolepine (CRY) is a pharmacologically active
plant alkaloid; it has significant potential as an antiprotozoal and antibacterial under different
in vitro and in vivo conditions. The fluorescence assay was used for evaluating the inhibitory
effect of CRY on four Babesia species and Theileria equi in vitro, and on the multiplication of
B. microti in mice. The toxicity assay was evaluated on Madin–Darby bovine kidney
(MDBK), mouse embryonic fibroblast (NIH/3T3), and human foreskin fibroblast (HFF) cell
lines. The half-maximal inhibitory concentration (IC50) values of CRY on Babesia bovis, B.
bigemina, B. divergens, B. caballi, and T. equi were 1740 ± 0.377, 1400 ± 0.6, 790 ± 0.32,
600 ± 0.53, and 730 ± 0.025 nM, respectively. The toxicity assay on MDBK, NIH/3T3, and
HFF cell lines showed that CRY affected the viability of cells with a half-maximum effective
concentration (EC50) of 86.67 ± 4.43, 95.29 ± 2.7, and higher than 100 μM, respectively. In
mice experiments, CRY at a concentration of 5 mg/kg effectively inhibited the growth of B.
microti, while CRY–atovaquone (AQ) and CRY–DA combinations showed higher chemotherapeutic
effects than CRY alone. Our results showed that CRY has the potential to be an
alternative remedy for treating piroplasmosis.