Ellagic acid microspheres restrict the growth of Babesia and Theileria in vitro and Babesia microti in vivo

Table 1 The IC₅₀ and selectivity index of EA, β-CD EA and APSP EA

Compound	Parasite	IC₅₀ (µM)^a	EC₅₀ (µM)^b			Selective indices^c
Compound	Parasite	IC₅₀ (µM)^a	MDBK	NIH/3T3	HFF	MDBK	NIH/3T3	HFF
EA	B. bovis	9.6 ± 1.5	> 800	> 800	> 800	> 83.3	> 83.3	> 83.3
	B. bigemina	7.9 ± 5.8				> 101.3	> 101.3	> 101.3
	B. divergens	5.4 ± 2.8				> 148.1	> 148.1	> 148.1
	B. caballi	3.3 ± 0.4				> 242.4	> 242.4	> 242.4
	T. equi	7.5 ± 0.6				> 106.7	> 106.7	> 106.7
	P. falciparum	330 nM^d
	L. major	9.8 μg/ml^e
β-CD EA	B. bovis	8.8 ± 0.53	> 800	> 800	> 800	> 90.9	> 90.9	> 90.9
	B. bigemina	18.9 ± 0.02				> 42.3	> 42.3	> 42.3
	B. divergens	11.0 ± 0.4				> 72.7	> 72.7	> 72.7
	B. caballi	4.4 ± 0.6				> 181.8	> 181.8	> 181.8
	T. equi	9.1 ± 1.7				> 87.9	> 87.9	> 87.9
APSP EA	B. bovis	4.2 ± 0.4	> 800	> 800	790 ± 5.4	> 190.5	> 190.5	188.1
	B. bigemina	9.6 ± 0.6				> 83.3	> 83.3	82.3
	B. divergens	2.6 ± 1.3				> 307.7	> 307.7	303.8
	B. caballi	0.9 ± 5.8				> 888.9	> 888.9	877.8
	T. equi	7.3 ± 0.5				> 109.6	> 109.6	108.2

^aHalf-maximal inhibition concentration of EA, β-CD EA and APSP EA on the in vitro culture of parasites. The value was determined from the dose-response curve using non-linear regression (curve fit analysis). The values are the means of experiments in triplicate
^bHalf-maximal effective concentration of EA, β-CD EA and APSP EA on cell lines. The values were determined from the dose-response curve using non-linear regression (curve fit analysis). The values are the means of experiments in triplicate
^cRatio of the EC₅₀ of cell lines to the IC₅₀ of each species. High numbers are favorable
^d[7]
^e[14]
Abbreviations: EA, ellagic acid; β-CD EA, β-cyclodextrin ellagic acid; APSP EA, antisolvent precipitation with a syringe pump prepared ellagic acid; MDBK, Madin–Darby bovine kidney; NIH/3T3, mouse embryonic fibroblast; HFF, human foreskin fibroblast