Effect of tanshinone IIA on the noncovalent interaction between warfarin and human serum albumin studied by electrospray ionization mass spectrometry.
Enhanced anticoagulation and/or even bleeding are often observed when patients on long-term warfarin (WAR) therapy consumed Danshen, a well-known medicinal herb in traditional Chinese medicine (TCM). This study demonstrates that altered WAR metabolism, arising from its interaction with the active components in Danshen, played a significant role in this curative effect. Mass spectrometric techniques including ESI-ITMS (electrospray ionization ion-trap mass spectrometry) and ESI-TOF (time-of-flight)-MS have been developed for the study of such drug-herb interactions. The experimental approach involved a detailed analysis and comparison of WAR metabolites in vivo from blood or urine of rats that had been orally administrated with WAR, either singly or together with the representative bioactive component of Danshen-lipid soluble TIIA (Tanshinon IIA), and a study of the interaction of human serum albumin (HSA), WAR, and water-soluble sodium tanshinone IIA sulfonate (STS) in vitro. Results demonstrate that TIIA accelerates the metabolic rate of WAR, whereas STS displaces WAR from the WAR-HSA complex, resulting in an increase of free WAR concentration in blood. It is suggested that the elevated level and enhanced metabolism of WAR is responsible for the over-anticoagulation effect observed.
Liu
Jie
J
Department of Chemistry and The Key Laboratory of Analytical Science of MOE, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China.
Wang
Xiaoru
X
Cai
Zongwei
Z
Lee
Frank S C
FS
D045784:Abietanes; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D041743:Herb-Drug Interactions; D006801:Humans; D008297:Male; D010616:Phenanthrenes / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D014859:Warfarin / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics
D045784:Abietanes; D004365:Drugs, Chinese Herbal; D010616:Phenanthrenes; D012709:Serum Albumin; C021751:tanshinone; D014859:Warfarin