Absorption and disposition of ginsenosides after oral administration of Panax notoginseng extract to rats.
Panax notoginseng (Sanqi) is a cardiovascular herb containing ginsenosides that are believed to be responsible for the therapeutic effects of Sanqi. The aim of this study was to evaluate rat exposure to ginsenosides after oral administration of Sanqi extract and to identify the key factors affecting their absorption and disposition. Ginsenosides were administered to rats, either in the form of Sanqi extract or as pure chemicals. The ginsenosides Ra(3), Rb(1), Rd, Re, Rg(1), and notoginsenoside R(1) were the major saponins present in the herbal extract. Systemic exposure to ginsenosides Ra(3), Rb(1), and Rd after oral administration of the extract was significantly greater than that to the other compounds. Considerable colonic deglycosylation of the ginsenosides occurred, but the plasma levels of deglycosylated metabolites were low in rats. Poor membrane permeability and active biliary excretion are the two primary factors limiting systemic exposure to most ginsenosides and their deglycosylated metabolites. In contrast with other ginsenosides, biliary excretion of ginsenosides Ra(3) and Rb(1) was passive. Meanwhile, the active biliary excretion of ginsenoside Rd was significantly slower than that of other saponins. Slow biliary excretion, inefficient metabolism, and slow renal excretion resulted in long-circulating and thus relatively high exposure levels for these three ginsenosides. For these reasons, plasma ginsenosides Ra(3), Rb(1), and Rd were identified as pharmacokinetic markers for indicating rat systemic exposure to Sanqi extract. This is a systematic investigation of the absorption and disposition of ginsenosides from an herb, the information gained from which is important for linking Sanqi administration to its medicinal effects.
Liu
Houfu
H
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhangjiang Hi-Tech Park, Shanghai 201203, China.
Yang
Junling
J
Du
Feifei
F
Gao
Xiumei
X
Ma
Xutao
X
Huang
Yuhong
Y
Xu
Fang
F
Niu
Wei
W
Wang
Fengqing
F
Mao
Yu
Y
Sun
Yan
Y
Lu
Tong
T
Liu
Changxiao
C
Zhang
Boli
B
Li
Chuan
C
D000284:Administration, Oral; D000818:Animals; D001646:Bile / Q000378:metabolism; D001711:Biotransformation; D018938:Caco-2 Cells; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002463:Cell Membrane Permeability; D003106:Colon / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D036145:Ginsenosides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006031:Glycosylation; D006801:Humans; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D007668:Kidney / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013329:Structure-Activity Relationship
D002317:Cardiovascular Agents; D004365:Drugs, Chinese Herbal; D036145:Ginsenosides; C519374:Panax notoginseng extract; C442759:ginsenoside Rb1; C049863:ginsenoside Rd