Table 6.

ADMET results of determined major compounds of Cistus villosus L. by LC-HRMS profiling.

Pharmacokinetics	Ellagic acid	Kaempferol	Quercetin	Rutin	Apigenin
Absorption
Water solubility (mg/L)	922.46	127.30	-	217.20	159.88
Caco-2 cell permeability (nm/s)	20.48	9.57	−5.20	7.91	10.54
Human intestinal absorption (HIA)	61.39	79.43	0.01	2.86	88.12
Distribution
BBB penetration (C. brain/C. blood)	0.32	0.28	0.008	0.02	0.56
Plasma protein binding (%)	88.40	89.60	95.49	43.89	97.25
Metabolism
CYP3A4 substrate	NO	NO	NO	YES	NO
CYP2C19 inhibitor	NO	NO	NO	NO	NO
CYP2C9 inhibitor	NO	NO	NO	NO	NO
CYP2D6 inhibitor	NO	YES	NO	NO	YES
CYP3A4 inhibitor	NO	YES	NO	NO	YES
Excretion
T ½ (hour)	0.886	0.905	0.929	0.52	0.856
CL (mL/min/kg)	3.724	6.868	8.284	1.34	7.022
Toxicity
Human hepatotoxicity	YES	YES	-	YES	YES
Carcinogens	NO	NO	-	NO	NO
HERG inhibition	NO	NO	-	NO	NO
Pharmacokinetics	Naringenin	Hispidulin 7-O-glucoside	Dihydrokaempferol	(−)-Epicatechin gallate	(+)-Catechin
Absorption
Water solubility (mg/L)	251.40	2.55	319.73	126.98	1.74
Caco-2 cell permeability (nm/s)	10.52	9.24	9.56	13.21	5.971
Human intestinal absorption (HIA)	87.31	42.14	77.83	40.58	0.096
Distribution
BBB penetration (C. brain/C. blood)	0.59	0.03	0.28	0.14	0.025
Plasma protein binding (%)	100	62.36	89.67	100	92.06
Metabolism
CYP3A4 substrate	YES	YES	NO	NO	YES
CYP2C19 inhibitor	NO	YES	NO	NO	NO
CYP2C9 inhibitor	NO	YES	NO	NO	NO
CYP2D6 inhibitor	NO	NO	NO	NO	NO
CYP3A4 inhibitor	YES	YES	NO	NO	NO
Excretion
T ½ (hour)	0.774	0.51	0.625	0.923	0.853
CL (mL/min/kg)	17.388	2.64	8.968	17.814	17.911
Toxicity
Human hepatotoxicity	NO	NO	NO	NO	YES
Carcinogens	NO	NO	NO	NO	NO
HERG inhibition	NO	NO	NO	NO	NO