Herb-drug interaction of Astragali Radix based on in vitro incubation and pharmacokinetic assessment.

BACKGROUND: Astragali Radix (AR) is extensively utilized in Asia for its various pharmacological effects. With the widespread use of AR, the risk of herb-drug interactions (HDIs) mediated by cytochrome P450 (P450) enzymes has become a serious concern. This study aims to investigate the regulatory effects of AR and its major components on P450 enzymes in vitro and in vivo to elucidate the potential HDIs and molecular mechanisms. METHODS: The inhibitory effects of AR extract and 15 major components on P450 enzymes were evaluated using rat liver microsomes and human liver microsomes (HLMs). The enzyme inhibitory kinetic parameters of these major components were determined. Additionally, animal studies were conducted to assess the effects of AR extract on the pharmacokinetics of probe substrates and on the protein expression of P450 enzymes. RESULTS: In vitro studies showed significant differences between rat and human liver microsomes in the inhibitory effects of AR extract and its major components on P450 enzymes. AR inhibited CYP1A2 and CYP2C9 in HLMs. Animal studies indicated that AR extract might weakly inhibit CYP1A2 and induce CYP2C6. WB experiments showed that AR had no significant impact on the protein expression of P450 enzymes. CONCLUSIONS: The results indicated that the AR extract and various major components may regulate CYP1A2, CYP2C9, and CYP2C19 (CYP2C6 in rat) activities. These findings provide valuable insights for predicting AR-related HDIs and support the development of traditional Chinese medicine. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12906-025-05085-5.