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 CES1 A,CES2A,CYPs1 A,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(3g/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.