Modulation of esterified drug metabolism by tanshinones from Salvia miltiorrhiza ("Danshen")

M. Jason Hatfield, Lyudmila G. Tsurkan, Janice L. Hyatt, Carol C. Edwards, Andrew Lemoff, Cynthia Jeffries, Bing Yan, Philip M. Potter

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

The roots of Salvia miltiorrhiza ("Danshen") are used in traditional Chinese medicine for the treatment of numerous ailments including cardiovascular disease, hypertension, and ischemic stroke. Extracts of S. miltiorrhiza roots in the formulation "Compound Danshen Dripping Pill" are undergoing clinical trials in the United States. To date, the active components of this material have not been conclusively identified. We have determined that S. miltiorrhiza roots contain potent human carboxylesterase (CE) inhibitors, due to the presence of tanshinones. Ki values in the nM range were determined for inhibition of both the liver and intestinal CEs. As CEs hydrolyze clinically used drugs, the ability of tanshinones and S. miltiorrhiza root extracts to modulate the metabolism of the anticancer prodrug irinotecan (CPT-11) was assessed. Our results indicate that marked inhibition of human CEs occurs following incubation with both pure compounds and crude material and that drug hydrolysis is significantly reduced. Consequently, a reduction in the cytotoxicity of irinotecan is observed following dosing with either purified tanshinones or S. miltiorrhiza root extracts. It is concluded that remedies containing tanshinones should be avoided when individuals are taking esterified agents and that patients should be warned of the potential drug-drug interaction that may occur with this material.

Original languageEnglish (US)
Pages (from-to)36-44
Number of pages9
JournalJournal of Natural Products
Volume76
Issue number1
DOIs
Publication statusPublished - Jan 25 2013

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ASJC Scopus subject areas

  • Complementary and alternative medicine
  • Molecular Medicine
  • Organic Chemistry
  • Analytical Chemistry
  • Pharmaceutical Science
  • Pharmacology
  • Drug Discovery

Cite this

Hatfield, M. J., Tsurkan, L. G., Hyatt, J. L., Edwards, C. C., Lemoff, A., Jeffries, C., ... Potter, P. M. (2013). Modulation of esterified drug metabolism by tanshinones from Salvia miltiorrhiza ("Danshen"). Journal of Natural Products, 76(1), 36-44. https://doi.org/10.1021/np300628a