Abstract: OBJECTIVE   To investigate the effects of prenylated compounds derived from Psoralea corylifolia against human CYP1A1, and validate the obtained results by molecular docking.METHODS   7-Ethoxyresorufin was used as the probe substrate for human CYP1A1. In addition, the ultra-high performance liquid chromatography tandem triple quadrupole mass spectrometry (UHPLC-TQD-MS) conditions for resorufin (the specific metabolite of 7-ethoxyresorufin by CYP1A1) were optimized. Based on the optimized condition, 7-ethoxyresorufin was incubated with CYP1A1 in the absence (control) and presence of bavachin, psoralidin, isobavachalcone, isobavachin and bavachinin at different concentration (1, 10, 100 μmol·L^-1), respectively. Three kinetic models were applied to calculate the K_ivalues by nonlinear regression for competitive inhibition, noncompetitive inhibition, and mixed-type inhibition, respectively. The molecular docking between prenylated compounds and CYP1A1 was performed by Autodock 4.2.RESULTS   These findings demonstrated that bavachin, psoralidin, isobavachalcone, isobavachin and bavachinin exhibited potent inhibitory effects against CYP1A1, and the corresponding IC₅₀values were 0.28, 0.49, 0.36, 2.24, 4.07 μmol·L^-1, respectively. Based on the smallest Akaike information criterion (AIC) and Schwarz criterion (SC) principles, bavachin and isobavachalcone exerted competitive inhibition against CYP1A1 with K_i values of 0.12 and 0.23 μmol·L^-1, respectively, while psoralidin displayed noncompetitive inhibitory effects against CYP1A1(K_i=0.59 μmol·L^-1). Molecular docking results indicated that hydrogen bond, π-π bond and hydrophobic interaction could be formed between bavachin (or isobavachalcone) and CYP1A1 protein crystals, and their binding free energies were -10.145 and -8.286 kcal·mol^-1(1 kcal=4.2 kJ), respectively. This might be the reason why these compounds have strong affinity with CYP1A1, and thus produce strong inhibitory activity.CONCLUSION   Prenylated compounds in Psoralea corylifolia are identified as potent inhibitors for CYP1A1 (IC₅₀ < 5 μmol·L^-1). When dehydration reaction occurrs in bonds 1 and 2, the inhibitory effects of herbal compounds against CYP1A1 increases. Herbal compounds with isopentene group at C-6 position exhibits stronger inhibitory effects against CYP1A1 than those with isopentene group at C-8 position. Herbal compounds with C-7-OCH₃ displays weaker inhibitory effects against CYP1A1 than those with C-7-OH. The molecular docking results also validates the presence of strong affinity between bavachin (or isobavachalcone) and CYP1A1 protein.