A mechanistic study of the intestinal absorption of crypotanshinone, the major active constituent of Saliva miltiorrhiza

Zhang, Jing, Huang, Min, Guan, Su, Bi, Hui-Chang, Pan, Ying, Duan, Wei, Chan, Sui Yung, Chen, Xiao, Hong, Yun-Han and Zhou, Shufeng 2006, A mechanistic study of the intestinal absorption of crypotanshinone, the major active constituent of Saliva miltiorrhiza, Journal of pharmacology and experimental therapeutics, vol. 317, no. 3, pp. 1285-1294.

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Title A mechanistic study of the intestinal absorption of crypotanshinone, the major active constituent of Saliva miltiorrhiza
Formatted title Mechanistic study of the intestinal absorption of crypotanshinone, the major active constituent of Saliva miltiorrhiza
Author(s) Zhang, Jing
Huang, Min
Guan, Su
Bi, Hui-Chang
Pan, Ying
Duan, Wei
Chan, Sui Yung
Chen, Xiao
Hong, Yun-Han
Zhou, Shufeng
Journal name Journal of pharmacology and experimental therapeutics
Volume number 317
Issue number 3
Start page 1285
End page 1294
Publisher American Association for Pharmacology Experimental Therapeutics
Place of publication Bethesda, Md.
Publication date 2006-06
ISSN 0022-3565
Summary The nature of intestinal absorption of most herbal medicine is unknown. Cryptotanshinone (CTS) is the principal active constituent of the widely used cardiovascular herb Salvia miltiorrhiza (Danshen). We investigated the oral bioavailability of CTS in rats and the mechanism for its intestinal absorption using several in vitro and in vivo models:1) Caco-2 cell monolayers; 2) monolayers of MDCKII cells overexpressing P-glycoprotein
(PgP); and 3) single-pass rat intestinal perfusion with mesenteric vein cannulation. The systemic bioavailabilities of CTS after oral and intraperitoneal administration at 100 mg/kg were 2.05 and 10.60%, respectively. In the perfused rat intestinal model, permeability coefficients based on CTS disappearance from the luminal perfusate (Plumen) were 6.7- to 10.3-fold higher than permeability coefficients based on drug appearance in venous blood (Pblood). Pblood significantly increased in the presence of the P-gP inhibitor, verapamil. CTS transport across Caco-2 monolayers was pH-, temperature- and ATP-dependent. The transport from the apical (AP) to the basolateral (BL) side was 3- to 9-fold lower than that from the BL to the AP side. Inclusion of verapamil (50 µM) in both AP and BL sides abolished the polarized CTS transport across Caco-2 cells. Moreover, CTS was significantly more permeable in the BL to AP than in the AP to BL direction in MDCKII and MDR1-MDCKII cells. The permeability coefficients in the BL to AP direction were significantly higher in MDCKII cells overexpressing PgP. These findings indicate that CTS is a substrate for PgP that can pump CTS into the luminal side.
Language eng
Field of Research 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2006, The American Society for Pharmacology and Experimental Therapeutics
Persistent URL http://hdl.handle.net/10536/DRO/DU:30009157

Document type: Journal Article
Collection: School of Medicine
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