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Research ArticleArticle

Absorption and Disposition of Ginsenosides after Oral Administration of Panax notoginseng Extract to Rats

Houfu Liu, Junling Yang, Feifei Du, Xiumei Gao, Xutao Ma, Yuhong Huang, Fang Xu, Wei Niu, Fengqing Wang, Yu Mao, Yan Sun, Tong Lu, Changxiao Liu, Boli Zhang and Chuan Li
Drug Metabolism and Disposition December 2009, 37 (12) 2290-2298; DOI: https://doi.org/10.1124/dmd.109.029819
Houfu Liu
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Junling Yang
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Feifei Du
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Xiumei Gao
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Xutao Ma
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Yuhong Huang
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Fang Xu
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Wei Niu
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Fengqing Wang
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Yu Mao
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Yan Sun
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Tong Lu
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Changxiao Liu
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Boli Zhang
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Chuan Li
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Abstract

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 Ra3, Rb1, Rd, Re, Rg1, and notoginsenoside R1 were the major saponins present in the herbal extract. Systemic exposure to ginsenosides Ra3, Rb1, 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 Ra3 and Rb1 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 Ra3, Rb1, 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.

Footnotes

  • This work was supported in part by the National Basic Research Program of China [Grant 2005CB523403]; the National Science and Technology Major Project of China “Key New Drug Creation and Manufacturing Program” [Grant 2009ZX09304-002]; the National Science Fund of China for Distinguished Young Scholars [Grant 30925044]; the National Natural Science Foundation of China [Grant 90209044]; and the Shanghai Science and Technology Major Project [Grant 08DZ1980200].

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

    doi:10.1124/dmd.109.029819

  • ppd-type
    20(S)-protopanaxadiol type
    ppt-type
    20(S)-protopanaxatriol type
    PK
    pharmacokinetic
    GRb1
    ginsenoside Rb1
    GRd
    ginsenoside Rd
    GRg3
    ginsenoside Rg3
    GF2
    ginsenoside F2
    GRh2
    ginsenoside Rh2
    GRe
    ginsenoside Re
    GRg1
    ginsenoside Rg1
    GRf
    ginsenoside Rf
    GF1
    ginsenoside F1
    NGR1
    notoginsenoside R1
    C-K
    compound-K
    Ppd
    protopanaxadiol
    Ppt
    protopanaxatriol
    GRa3
    ginsenoside Ra3
    GRc
    ginsenoside Rc
    20gRf
    20-gluco-ginsenoside Rf
    GRh1
    ginsenoside Rh1
    GRg2
    ginsenoside Rg2
    MK571
    3-[[3-[2-(7-chloroquinolin-2-yl)vinyl]phenyl]-(2-dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid
    AUC
    area under concentration-time curve
    CLB
    biliary clearance
    CLR
    renal clearance
    Cum.Ae
    cumulative amount excreted during sampling period
    Papp
    apparent permeability coefficient
    P-gp
    P-glycoprotein
    MRP2
    multidrug resistance-associated protein 2
    S
    aqueous solubility at a given pH
    TPSA
    topological polar surface area
    LC
    liquid chromatography
    t1/2
    elimination half-life
    CLtot,p
    total plasma clearance
    QSPKR
    quantitative structure-PK relationships.

    • Received August 5, 2009.
    • Accepted September 23, 2009.
  • Copyright © 2009 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 37 (12)
Drug Metabolism and Disposition
Vol. 37, Issue 12
1 Dec 2009
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Research ArticleArticle

Absorption and Disposition of Ginsenosides after Oral Administration of Panax notoginseng Extract to Rats

Houfu Liu, Junling Yang, Feifei Du, Xiumei Gao, Xutao Ma, Yuhong Huang, Fang Xu, Wei Niu, Fengqing Wang, Yu Mao, Yan Sun, Tong Lu, Changxiao Liu, Boli Zhang and Chuan Li
Drug Metabolism and Disposition December 1, 2009, 37 (12) 2290-2298; DOI: https://doi.org/10.1124/dmd.109.029819

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Research ArticleArticle

Absorption and Disposition of Ginsenosides after Oral Administration of Panax notoginseng Extract to Rats

Houfu Liu, Junling Yang, Feifei Du, Xiumei Gao, Xutao Ma, Yuhong Huang, Fang Xu, Wei Niu, Fengqing Wang, Yu Mao, Yan Sun, Tong Lu, Changxiao Liu, Boli Zhang and Chuan Li
Drug Metabolism and Disposition December 1, 2009, 37 (12) 2290-2298; DOI: https://doi.org/10.1124/dmd.109.029819
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