Effects of Traditional Herbal Formulae on Human CYP450 Isozymes

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 CYP450isozymes（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 CYP2C19activity（IC50：SJZD,83.28μg/m L;SWD,235.54μg/m L;BWD,166.82μg/m L;SDD,178.19μg/m L）;SJZD（IC50=196.46μg/m L）,SWD（IC50=333.42μg/m L）and SDD（IC50=163.42μg/m L）inhibited CYP2E1-mediated metabolism;whereas BWD exhibited comparatively weak inhibition of CYP2E1（IC50=501.78μg/m L）.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.

Inhibitory potential of three Yin-tonification herbal formulas on the activities of human major cytochrome P450 and UDP-glucuronosyltransferases isozymes in vitro

OBJECTIVE:To investigate the influence of Yin-tonification herbal formulas Jaeumganghwa-tang(Ziyin Jianghuo Tang,JEGHT),Ssanghwa-tang(Shuanghe Tang,SHT) and Yukmijihwang-tang(Liuwei Di huang Tang,YMJHT) on the activities of human major cytochrome P450(CYP450 s) and UDP-glucuronosyltransferases isozymes(UGTs) in vitro.METHODS:The activities of CYP450 s(CYP1 A2,CYP3 A4,CYP2 B6,CYP2 C9,CYP2 C19,CYP2 D6 and CYP2 E1) and UGTs(UGT1 A1,UGT1 A4 and UGT2 B7)were assessed using in vitro fluorescence-and luminescence-based enzyme assays,respectively.The effects of herbal formulas on the activities of CYP450 s and UGTs were presented as IC50 values.RESULTS:JEGHT showed the potent inhibition of the CYP2 D6 activity,with weak inhibition on the activities of CYP1 A2,CYP2 B6,CYP2 C9,CYP2 C19,CYP2 E1,CYP3 A4,UGT1 A1,UGT1 A4 and UGT2 B7.SHT inhibited the activities of CYP1 A2 and CYP2 E1,whereas the negligible inhibition of the activities of CYP2 B6,CYP2 C9,CYP2 C19,CYP2 D6,CYP3 A4,UGT1 A1,UGT1 A4 and UGT2 B7 through SHT was observed.YMJHT inhibited CYP2 E1 activity,with a negligible inhibition on the activities of CYP1 A2,CYP2 B6,CYP2 C9,CYP2 C19,CYP2 D6,CYP3 A4,UGT1 A1,UGT1 A4 and UGT2 B7.CONCLUSION:These findings provide information about the potential interactions between three Yin-tonification herbal formulas and conventional drugs.