title: Combinatorial metabolism notably affects human systemic exposure to ginsenosides from orally administered extract of Panax notoginseng roots (Sanqi).
abstract: Ginsenosides are medicinal ingredients of the cardiovascular herb Panax notoginseng roots (Sanqi). Here, we implemented a human study (ChiCTR-ONC-09000603; www.chictr.org) to characterize pharmacokinetics and metabolism of ginsenosides from an orally ingested Sanqi-extract (a 1:10 water extract of Sanqi) and the human plasma and urine samples were analyzed by liquid chromatography-mass spectrometry. Plasma and urinary compounds derived from ginsenosides included: 1) intestinally absorbed ginsenosides Ra3, Rb1, Rd, F2, Rg1, and notoginsenoside R1; and 2) the deglycosylated products compound-K, 20(S)-protopanaxadiol, 20(S)-protopanaxatriol, and their oxidized metabolites. The systemic exposure levels of the first group compounds increased as the Sanqi-extract dose increased, but those of the second group compounds were dose-independent. The oxidized metabolites of 20(S)-protopanaxadiol and 20(S)-protopanaxatriol represented the major circulating forms of ginsenosides in the bloodstream, despite their large interindividual differences in exposure level. The metabolites were formed via combinatorial metabolism that consisted of a rate-limiting step of ginsenoside deglycosylation by the colonic microflora and a subsequent step of sapogenin oxidation by the enterohepatic cytochrome P450 enzymes. Significant accumulation of plasma ginsenosides and metabolites occurred in the human subjects receiving 3-week subchronic treatment with the Sanqi-extract. Plasma 20(S)-protopanaxadiol and 20(S)-protopanaxatriol could be used as pharmacokinetic markers to reflect the subjects' microbial activities, as well as the timely-changes and interindividual differences in plasma levels of their respective oxidized metabolites. The information gained from the current study is relevant to pharmacology and therapeutics of Sanqi.
authors: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors: Zheyi
authors: Z
authors: Hu
authors: Junling
authors: J
authors: Yang
authors: Chen
authors: C
authors: Cheng
authors: Yuhong
authors: Y
authors: Huang
authors: Feifei
authors: F
authors: Du
authors: Fengqing
authors: F
authors: Wang
authors: Wei
authors: W
authors: Niu
authors: Fang
authors: F
authors: Xu
authors: Rongrong
authors: R
authors: Jiang
authors: Xiumei
authors: X
authors: Gao
authors: Chuan
authors: C
authors: Li
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D005260:Female; D036145:Ginsenosides / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D008297:Male; D053723:Panax notoginseng; D010936:Plant Extracts / Q000008:administration & dosage / Q000378:metabolism*; D018517:Plant Roots; D012502:Sapogenins / Q000378:metabolism
chemical_list: D036145:Ginsenosides; D010936:Plant Extracts; D012502:Sapogenins; C081552:protopanaxatriol; C112772:ginsenoside compound K; C062916:protopanaxadiol