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

Feng Zhang1, Wei Liu2, Jian Huang1,3, Qi-long Chen1, Dan-dan Wang4, Li-wei Zou1, Yong-fang Zhao1,2, Wei-dong Zhang1, Jian-guang Xu1, Hong-zhuan Chen1, Guang-bo Ge1
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
Correspondence to: Hong-zhuan Chen:, Guang-bo Ge:,
DOI: 10.1038/s41401-021-00697-2
Received: 3 December 2020
Accepted: 12 May 2021
Advance online: 28 June 2021


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.

Keywords: herbal extract of Jingyin granules (HEJG); cytochrome P450 enzymes (CYPs/P450s); herb–drug interactions (HDIs); CYP3A substrate-drugs

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