title: Metabolism-mediated drug interaction potential of HS-23, a new herbal drug for the treatment of sepsis in human hepatocytes and liver microsomes.
abstract: HS-23, an extract of the dried flower buds of Lonicera japonica, is a new botanical drug currently being evaluated in a phase I clinical study in Korea for the treatment of sepsis. The in vitro induction and inhibition potentials of HS-23 on the drug-metabolizing enzymes using human hepatocytes and liver microsomes were assessed to evaluate herb-drug interaction according to botanical drug guideline and drug interaction guidance of FDA. HS-23 slightly inhibited CYP2A6, CYP2B6, CYP2C9, CYP2C19, and CYP3A4 enzyme activities in human liver microsomes with IC50 values of 80.6, 160.7, 169.5, 85.4, and 76.6 μg/mL, respectively. HS-23 showed negligible inhibition of CYP1A2, CYP2C8, CYP2D6, UGT1A1, UGT1A4, UGT1A9, and UGT2B7 activities in human liver microsomes. Based on these results, HS-23 may not inhibit the metabolism of CYP2A6, CYP2B6, CYP2C9, CYP2C19, and CYP3A4-catalyzed drugs in humans. HS-23 did not affect the mRNA expression of CYP1A2, CYP2B6, and CYP3A4 after 48 h treatment at three concentrations (0.5, 5, and 50 μg/mL) in three independent human hepatocytes, indicating that HS-23 has no effect on herb-drug interactions that up- or down-regulate CYP1A2, CYP2B6, and CYP3A4. These results indicate that the administration of HS-23 in human may not cause clinically relevant inhibition and induction of these cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes and HS-23 may be promising therapeutic agent for treatment of sepsis.
authors: College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon, Gyeonggi-do, 420-743, Republic of Korea.
authors: Hyeon-Uk
authors: HU
authors: Jeong
authors: Ji Young
authors: JY
authors: Lee
authors: Soon-Sang
authors: SS
authors: Kwon
authors: Ju Hyun
authors: JH
authors: Kim
authors: Young-Mok
authors: YM
authors: Kim
authors: Sung-Woon
authors: SW
authors: Hong
authors: Sung Hum
authors: SH
authors: Yeon
authors: Sun-Mee
authors: SM
authors: Lee
authors: Yong-Yeon
authors: YY
authors: Cho
authors: Hye Suk
authors: HS
authors: Lee
mesh_terms: D002853:Chromatography, Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology*; D041743:Herb-Drug Interactions; D006801:Humans; D008658:Inactivation, Metabolic; D031239:Lonicera / Q000737:chemistry; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D018805:Sepsis / Q000188:drug therapy*; D053719:Tandem Mass Spectrometry
chemical_list: D010936:Plant Extracts; C588038:lonicerae flos; D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase