title: In vitro and in vivo assessment of cytochrome P450-mediated herb-drug interaction of Ssang-hwa-tang.
abstract: We have evaluated the herb-drug interaction potential of Ssang-hwa-tang (SHT) mediated by cytochrome P450 (CYP) inhibition/induction. Further, the effects of fermentation on the CYP-mediated herb-drug interaction potential were determined. SHT showed inhibitory activity toward CYP1A2, but not 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, and 3A4 in human liver microsomes. The results of the enzyme kinetic study suggested that the SHT-induced CYP1A2 inhibition is mixed reversible inhibition. The hepatic CYP expression and activity in rats treated with SHT were examined. The expression/activity of CYP2E1 increased as a result of SHT extract treatment (P<0.005 or P<0.001, respectively), which raises the possibility that SHT may increase the toxicity of environmental toxicants through the elevation of CYP2E1-mediated metabolic activation. SHT fermentation using Lactobacillus fermentum or Lactobacillus gasseri resulted in attenuation of the SHT-induced CYP1A2 inhibition, but not CYP2E1 induction, suggesting that changes in the chemical composition of SHT through fermentation can affect the inhibition of CYP1A2 activity.
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Sang Yoon
authors.initials: SY
authors.lastname: Lee
authors.forename: Ji-Yoon
authors.initials: JY
authors.lastname: Lee
authors.forename: Wonku
authors.initials: W
authors.lastname: Kang
authors.forename: Kwang-il
authors.initials: KI
authors.lastname: Kwon
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Oh
authors.forename: Jin Yeul
authors.initials: JY
authors.lastname: Ma
authors.forename: Sang Kyum
authors.initials: SK
authors.lastname: Kim
mesh_terms: D000818:Animals; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000009:adverse effects* / Q000737:chemistry / Q000378:metabolism; D005285:Fermentation; D041743:Herb-Drug Interactions; D006801:Humans; D007700:Kinetics; D007778:Lactobacillus / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D004365:Drugs, Chinese Herbal; D003577:Cytochrome P-450 Enzyme System