Biological Activities and Pharmacokinetics of Praeruptorins from Peucedanum Species: A Systematic Review
Table 3
Summary of reported pharmacokinetic and tissue distribution studies of praeruptorins.
Compounds
Pharmacokinetic and tissue distribution studies
References
Pd-la
In vivo (in rat): a single dose administration (i.v.) of 5, 10, and 20 mg/kg Pd-la showed that it was quickly distributed and then eliminated from plasma. The main distribution tissues of Pd-Ia were spleen, heart, and lung; Pd-Ia was enabled to cross the blood-brain barrier due to low polarity.
In vivo (in rat): a single dose administration (i.v.) of 5 mg/kg Pd-la to rats with liver cirrhosis showed that the decreased metabolic clearance of Pd-la was at least partly due to the diminished levels of CYP3A1 and 3A2.
In vitro (in RLMs): CYP3A1/2 was the main isoform mediating both hydrolysis and oxidation. The major metabolite of Pd-la was (M1) -angeloyloxy-hydroxyl-,dihydroseselin.
In vitro (in human colon adenocarcinoma cells, LS174T): except Pra-E, praeruptorins significantly stimulated CAR and CYP3A4 receptor gene expression in dose-dependent manner.
In vitro (in human colon adenocarcinoma cells, Caco-2): Pd-la was rapidly transported across Caco-2 cells and partly hydrolyzed and created two stereoisomers via removal of the acetyl group from C- position.
In vitro (in RLMs and HLMs): all the metabolites were generated in an NADPH-dependent manner. Oxidation and hydrolysis were two main metabolic pathways of Pra-D and (+)-Pra-E. RLMs had more potential in catalyzing metabolism of both Pra-D and (+)-Pra-E than HLMs. Metabolites B1 and E1 were identified as (−)-cis-khellactone.
In vitro (in rat): a single dose administration (i.v.) of 10, and 20 mg/kg Pra-D showed that it is divided into two-compartment pharmacokinetic model including the fast distribution phase (t1/2, 0.119–0.130 h) followed by a slow elimination phase (1/2, 2.408–2.640 h).
In vitro (in RLMs and HLMs): in the absence of NADPH-regenerating system, Pra-C remained unbroken; however, (−)-praeruptorin A yielded (R, R)--angeloyl-khellactone and (R, R)--angeloyl-khellactone by a carboxylesterase(s)-mediated process. In RLMs, both enantiomers were eliminated more rapidly than in HLMs.
In vitro (in RLMs and HLMs): hydrolysis of these praeruptorins in the presence of the NADPH-regenerating system (hepatic phase I isozymes) produced cis-khellactone with the absolute configurations.
In vitro (in HLMs): CYP3A4 was the main isoform mediating both hydrolysis and oxidation. (−)-cis-Khellactone as a major metabolite (M1) showed biphasic kinetics in HLMs.
