Inhibition of Re Du Ning Injection on Enzyme Activities of Rat Liver Microsomes Using Cocktail Method

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• 作者：Xiao-qian Xu^a ; ^b ; Ting Geng^b ; ^c ; ^d ; She-bing Zhang^a ; Dan-yu Kang^a ; ^d ; Yan-jing Li^a ; ^b ; ^c ; Gang Ding^a ; ^b ; ^c ; ^{dingg2000@126.com" class="auth_mail" title="E-mail the corresponding author} ; Wen-zhe Huang^a ; ^b ; ^c ; Zhen-zhong Wang^b ; ^c ; Wei Xiao^b ; ^c ; ^{kanionxw2010@126.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：cocktail ; cytochrome P450 ; inhibition ; rat liver microsomes ; Reduning Injection
• 刊名：Chinese Herbal Medicines
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：8
• 期：3
• 页码：231-241
• 全文大小：837 K

文摘

Re Du Ning Injection (RDN), a Chinese materia medica injection, is made from the extracts of Lonicerae Japonicae Flos, Gardeniae Fructus, and Artemisiae Annuae Herba. Since last decade, RDN has been widely used in China for the treatment of viral infection, fever, and inflammation. To assess the potential interacting of RDN with co-administered drugs, the inhibitory effects of RDN on the enzyme activities (CYP1A1, CYP1A2, CYP2C11, CYP2D1, and CYP3A1/2) of rat liver microsomes were investigated by a cocktail method.

Methods

A sensitive and specific LC-MS method capable of simultaneous quantification of five metabolites in rat liver microsomes was developed and validated. Then RDN (0.625%–1.0%) was incubated with rat liver microsomes and specific substrates. The enzyme activities were expressed as the formation rate of the specific metabolites of the substrates (pmol · mg · protein⁻¹ · min⁻¹).

Results

RDN competitively inhibited the activities of CYP1A2 and CYP2C11, with inhibition constant (K_i) values determined to be 0.18% and 0.63%, respectively. RDN exhibited the mixed inhibition on the activity of CYP2D1, with a K_i value of 0.15%. The activities of CYP1A1 and CYP3A1/2 were not markedly inhibited even by 1.0% RDN.

Conclusion

RDN could inhibit the rat enzyme activities of CYP1A2, 2C11, and 2D1 in vitro with different inhibition modes, which is worthy of promoting safety and efficacy of RDN.