ObjectiveTo investigate the mechanism by which the aqueous extract of Dictamni Cortex induces hepatotoxicity by regulating the expression of cytochrome P450 （CYP） 1A2 through the aryl hydrocarbon receptor （AHR） signaling pathway.MethodsThe 80 male Sprague Dawley （SD） rats were randomly divided into a blank group， high-dose （8.1g·kg^-1）， medium-dose （2.7 g·kg^-1）， and low-dose groups （0.9 g·kg^-1） of aqueous extract of Dictamni Cortex. The aqueous extract of Dictamni Cortex was intragastrically administered for three months， and a recovery period of one month was set. The level of aspartate aminotransferase （AST） and alanine aminotransferase （ALT） in rat serum was detected. The organ index of liver tissue was calculated. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in liver tissue. Real-time quantitative reverse transcription-polymerase chain reaction （Real-time PCR） was employed to screen for key metabolic enzymes in the liver tissue of rats during the drug administration period. Subsequently， the mRNA and protein expression levels of the screened key metabolic enzyme CYP1A2 and its related pathway molecules ［AHR， aryl hydrocarbon receptor nuclear translocator （ARNT）， heat shock protein 90 （HSP90）， p23 molecular chaperone protein （p23）， and AHR-interacting protein （AIP）］ were detected by Real-time PCR， Western blot， and immunohistochemistry （IHC） techniques.ResultsCompared with the blank group， the ALT and AST levels were significantly increased in the high-dose， medium-dose， and low-dose groups during the administration period （P<0.05， P<0.01） and were still significantly increased in the high-dose group during the recovery period （P<0.05）. The organ index was significantly increased in the high-dose， medium-dose， and low-dose groups during the administration period （P<0.05， P<0.01） and was significantly decreased in the high-dose group during the recovery period （P<0.05）. Histopathological observations revealed that during the administration period， the high-dose， medium-dose， and low-dose groups exhibited varying degrees of hepatocyte necrosis and inflammatory cell infiltration. During the recovery period， only a small number of inflammatory cells were observed in the high-dose group. During the administration period， the mRNA and protein expression level of CYP1A2 in the high-dose and medium-dose groups and AHR， ARNT， HSP90， and p23 in the low-dose， high-dose， and medium-dose groups was significantly increased （P<0.01）， while the expression of AIP was significantly decreased （P<0.01）. During the recovery period， the mRNA and protein expression level of CYP1A2， AHR， ARNT， HSP90， and p23 remained significantly elevated in the high-dose group （P<0.05， P<0.01）， and the expression of AIP was still significantly decreased （P<0.01）. Immunohistochemical results showed that the positive expression rate of CYP1A2 was significantly increased in the high-dose and medium-dose groups during the administration period （P<0.01） and remained significantly elevated in the high-dose group during the recovery period （P<0.01）.ConclusionCYP1A2 is a key metabolic enzyme for hepatotoxicity during the administration period and reversibility during the recovery period of aqueous extract of Dictamni Cortex， and its mechanism is related to the AHR signaling pathway.

aqueous extract of Dictamni Cortex;aryl hydrocarbon receptor（AHR） pathway;cytochrome P450 （CYP） 1A2;hepatotoxicity;metabolic enzyme