Inhibition of drug-metabolizing enzymes by Jingyin granules: implications of herb–drug interactions in antiviral therapy  

作　　者：Feng Zhang Wei Liu Jian Huang Qi-long Chen Dan-dan Wang Li-wei Zou Yong-fang Zhao Wei-dong Zhang Jian-guang Xu Hong-zhuan Chen Guang-bo Ge 

机构地区：[1]Institute of Interdisciplinary Integrative Medicine Research,Shanghai University of Traditional Chinese Medicine,Shanghai,201203,China [2]Institute of Liver Diseases,Shuguang Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai,201203,China [3]Pharmacology and Toxicology Division,Shanghai Institute of Food and Drug Control,Shanghai,201203,China [4]SPH Xing Ling Sci.&Tech.Pharmaceutical Co.,Ltd,Shanghai,201703,China

出　　处：《Acta Pharmacologica Sinica》2022年第4期1072-1081,共10页中国药理学报（英文版）

基　　金：This work was supported by Shanghai Science and Technology Innovation Action Plans(20S21901500,20S21900900)supported by Shanghai Science and Technology Committee;the NSF of China(81922070,81973286);the National Key Research and Development Program of China(2017YFC1700200,2017YFC1702000);the National Science and Technology Major Project of China(2018ZX09731016);the Three-year Action Plan of Shanghai TCM Development(ZY-(2018-2020)-CCCX-5001),Program of Shanghai Academic/Technology Research Leader(18XD1403600),Shuguang Program(18SG40);the Project on the Prevention and Treatment of COVID-19 with Chinese and Western Medicines supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission.

摘　　要：Jingyin granules, a marketed antiviral herbal medicine, have been recommended for treating H1N1 influenza A virus infection and Coronavirus disease 2019 (COVID-19) in China. To fight viral diseases in a more efficient way, Jingyin granules are frequently co-administered in clinical settings with a variety of therapeutic agents, including antiviral drugs, anti-inflammatory drugs, and other Western medicines. However, it is unclear whether Jingyin granules modulate the pharmacokinetics of Western drugs or trigger clinically significant herb–drug interactions. This study aims to assess the inhibitory potency of the herbal extract of Jingyin granules (HEJG) against human drug-metabolizing enzymes and to clarify whether HEJG can modulate the pharmacokinetic profiles of Western drug(s) in vivo. The results clearly demonstrated that HEJG dose-dependently inhibited human CES1A, CES2A, CYPs1A, 2A6, 2C8, 2C9, 2D6, and 2E1;this herbal medicine also time- and NADPH-dependently inhibited human CYP2C19 and CYP3A. In vivo tests showed that HEJG significantly increased the plasma exposure of lopinavir (a CYP3A-substrate drug) by 2.43-fold and strongly prolonged its half-life by 1.91-fold when HEJG (3 g/kg) was co-administered with lopinavir to rats. Further investigation revealed licochalcone A, licochalcone B, licochalcone C and echinatin in Radix Glycyrrhizae, as well as quercetin and kaempferol in Folium Llicis Purpureae, to be time-dependent CYP3A inhibitors. Collectively, our findings reveal that HEJG modulates the pharmacokinetics of CYP substrate-drug(s) by inactivating CYP3A, providing key information for both clinicians and patients to use herb–drug combinations for antiviral therapy in a scientific and reasonable way.

关 键 词：herbal extract of Jingyin granules(HEJG) cytochrome P450 enzymes(CYPs/P450s) herb-drug interactions(HDIs) CYP3A substrate-drugs 

分 类 号：R285.5[医药卫生—中药学]