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| Effects of Traditional Herbal Formulae on Human CYP450 Isozymes |
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| KeyWord:cytochrome P450, Sijunzi Decoction, Siwu decoction, Bawu Decoction, Shiquan Dabu Decoction, herb-drug interactions |
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| Abstract: |
| Objective: To assess the effects of traditional herbal formulae Sijunzi Decoction (四君子汤, Sagunja-tang, SJZD), Siwu Decoction (四物汤, Samul-tang, SWD), Bawu Decoction (八物汤, Palmul-tang, BWD) and Shiquan Dabu Decoction (十全大补汤, Sipjeondaebo-tang, SDD) on the activities of human cytochrome P450 (CYP450), a drug-metabolizing enzyme. Methods: Herbal formula water extracts were filtered and lyophilized after the powder extracts were dissolved in distilled water. The activities of major human CYP450 isozymes (CYP3A4, CYP2C19, CYP2D6 and CYP2E1) were measured using in vitro fluorescence-based enzyme assays. The inhibitory effects of the herbal formulas on the activities of CYP450 were characterized as half maximal inhibition concentration (IC50) values. Results: All the tested herbal formulae inhibited CYP2C19 activity (IC50: SJZD, 83.28 μg/mL; SWD, 235.54 μg/mL; BWD, 166.82 μg/mL; SDD, 178.19 μg/mL); SJZD (IC50 = 196.46 μg/mL), SWD (IC50 = 333.42 μg/mL) and SDD (IC50 = 163.42 μg/mL) inhibited CYP2E1-mediated metabolism; whereas BWD exhibited comparatively weak inhibition of CYP2E1 (IC50 = 501.78 μg/mL). None of the four herbal formulas significantly affected CYP3A4 or CYP2D6. Conclusions: These results suggest that SJZD, SWD, BWD and SDD could potentially inhibit the metabolism of co-administered synthetic drugs whose primary route of elimination is via CYP2C19. In addition, clinically relevant pharmacokinetic interactions could occur when SJZD, SWD or SDD is co-administered with drugs metabolized by CYP2E1. Our findings provide information for the safety and effective clinical use of these four classic herbal formulas. |
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