Metabolic Inhibition Evaluation of Anti-Ovarian Cancer Drug Candidate Praeruptorin E

Ovarian cancers remains to be one of the most severe diseases to threaten the health of humans, therefore, it is necessary to develop new chemical entities to treat ovarian. Praeruptorin E (PE) is an efficient anti-ovarian cancer drug isolated from Bai-hua Qian-hu (the dried roots of Peucedanum praeruptorum Dunn). The present study aims to evaluate the safety of PE from the view of inhibition of PE on the activity of important phase II drug-metabolizing enzymes (DMEs) UDP-glucuronosyltransferases (UGTs). The inhibition of PE on the activity of UGT1A isoforms expressed in both liver and intestine, UGT1A isoforms expressed specially in the intestine, and UGT2B isoforms were investigated. 100 mu M of PE inhibited 23.7, -71.9, 29, and 20.6% activity of UGT1A1, -1A3, -1A6, and -1A9, respectively. 100 mu M of PE inhibited the activity of UGT1A7, -1A8, -1A10 by 6.3, -152.9, and 23.6%, respectively. For the inhibition of PE on the activity of UGT2B isoforms, 100 mu M of PE inhibited UGT2B4, -2B7, and -2B15 by 45.7, 33.2, and 84.1%, respectively. Furthermore, concentration-dependent inhibition of PE on the activity of UGT2B15 was investigated, and 1, 5, 10, 20, 40, 60, 80, 100 mu M of PE inhibited UGT2B15 by -0.1, 12.1, 28.1, 36.3, 46.5, 53.8, 68, and 84.1%, respectively. In conclusion, herb-drug interaction (HDI) existed between PE-containing herbs and drugs mainly undergoing UGT2B15-catalyzed glucuronidation metabolism.