Adjunctive Intermittent Pneumatic Compression for Venous Thromboprophylaxis
Saudi Pharm J.
Alehaideb Z1, Chin KC2, Yao MC3, Law FCP2.
1 Department of Medical Genomics, King Abdullah International Medical Research Center/King Saud Bin Abdulaziz University for Health Sciences, PO Box 22490, Riyadh 11426, Saudi Arabia.
2 Department of Biological Sciences, Simon Fraser University, Burnaby, B.C. V5A 1S6, Canada.
3 School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong 510006, China.
Year of Publication:
Rhei rhizome (Rheum officinale Baill.) (RR) contains a large number of anthraquinone bioactive, yet little is known of the combined effect of these anthraquinones in a mixture. The goals of this study were: to determine the inhibitory potencies of individual anthraquinones and whole RR extract against human liver microsomal CYP1A2/3A4 activity, to predict the content of anthraquinones in RR using the concentration addition (CA) model, and to compare predicted and empirical contents in the same RR sample. Anthraquinone concentrations in the RR extract were determined using HPLC. The inhibitory potencies of individual anthraquinones were determined in incubations containing human liver microsomes. The study results were used to predict an effect-based dose measure of the anthraquinones in RR using the CA model. An empirical dose measure also was determined in the whole RR extract using the CYP1A2/3A4-based bioassay. For the CYP1A2-based studies, the predicted and empirical dose measures of anthraquinones were identical; they were 12.0 ± 1.80 and 12.20 ± 0.81 mg aloe-emodin equivalents/g RR, respectively. For the CYP3A4-based studies, the predicted and empirical dose measures were different; they were 2.80 ± 0.10 and 19.04 ± 0.41 mg aloe-emodin equivalents/g RR, respectively. Only the CYP1A2-based CA model which assumed additive effects of RR anthraquinones predicted an effect-based dose measure that was verifiable by empirical data. The CA model provides an alternative approach to the CYP1A2/3A4-based bioassay or empirical method to screen for the anthraquinones in RR. The CA model as described in this study is applicable to other botanical drugs, plant-based foods and dietary supplements.