title: Uptake and metabolism of ginsenoside Rh2 and its aglycon protopanaxadiol by Caco-2 cells.
abstract: The uptake and metabolism profiles of ginsenoside Rh2 and its aglycon protopanaxadiol (ppd) were studied in the human epithelial Caco-2 cell line. High-performance liquid chromatography-mass spectrometry was applied to determine Rh2 and its aglycon ppd concentration in the cells at different pH, temperature, concentration levels and in the presence or absence of inhibitors. Rh2 uptake was time and concentration dependent, and its uptake rates were reduced by metabolic inhibitors and influenced by low temperature, thus indicating that the absorption process was energy-dependent. Drug uptake was maximal when the extracellular pH was 7.0 for Rh2 and 8.0 for ppd. Rh2 kinetic analysis showed that a non-saturable component (Kd 0.17 nmol x h(-1) x mg(-1) protein) and an active transport system with a Km of 3.95 micromol x l(-1) and a Vmax of 4.78 nmol x h(-1) x mg(-1)protein were responsible for the drug uptake. Kinetic analysis of ppd showed a non-saturable component (Kd 0.78 nmol x h(-1) x mg(-1) protein). It was suggested that active extrusion of P-glycoprotein and drug degradation in the intestine may influence Rh2 bioavailability.
authors.affiliation: Key Laboratory of Pharmacokinetics, China Pharmaceutical University, 24 Tong Jia Xing Street, Nanjing, Jiangsu Province, China.
authors.forename: Hai-Tang
authors.initials: HT
authors.lastname: Xie
authors.forename: Guang-Ji
authors.initials: GJ
authors.lastname: Wang
authors.forename: Miao
authors.initials: M
authors.lastname: Chen
authors.forename: Xi-Ling
authors.initials: XL
authors.lastname: Jiang
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.forename: Hua
authors.initials: H
authors.lastname: Lv
authors.forename: Chen-Rong
authors.initials: CR
authors.lastname: Huang
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Michael
authors.initials: M
authors.lastname: Roberts
mesh_terms: D018938:Caco-2 Cells; D036145:Ginsenosides / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D012502:Sapogenins / Q000737:chemistry / Q000378:metabolism*; D014315:Triterpenes / Q000737:chemistry / Q000378:metabolism*
chemical_list: D036145:Ginsenosides; D012502:Sapogenins; D014315:Triterpenes; C055305:ginsenoside Rh2; C062916:protopanaxadiol