Modulation of Esterified Drug Metabolism by Tanshinones from Salvia miltiorrhiza (鈥淒anshen鈥?

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• 作者：M. Jason Hatfield ; Lyudmila G. Tsurkan ; Janice L. Hyatt ; Carol C. Edwards ; Andrew Lemoff ; Cynthia Jeffries ; Bing Yan ; Philip M. Potter
• 刊名：Journal of Natural Products
• 出版年：2013
• 出版时间：January 25, 2013
• 年：2013
• 卷：76
• 期：1
• 页码：36-44
• 全文大小：505K
• 年卷期：v.76,no.1(January 25, 2013)
• ISSN：1520-6025

文摘

The roots of Salvia miltiorrhiza (鈥淒anshen鈥? 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 鈥淐ompound Danshen Dripping Pill鈥?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. K_i 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鈥揹rug interaction that may occur with this material.