Gut Microbiota Mediated Metabolism and CYP1A1 Inhibition Effects of Scutellaria Barbata D. Don

OBJECTIVE   To study gut microbiota mediated the changes in the concentration of main chemical components of Scutellaria barbata D.Don (S. barbata) and the vary of its inhibitory effect on CYP1A1 enzyme.METHODS   Ultra-fast liquid chromatography coupled with quadrupole linear ion trap mass spectrometry (UPLC-Q-TRAP-MS) was established to quantify the constituents in co-incubation solution. CYP1A1 activity assay was used to detect the inhibitory effect of co-incubation extract, scutellarein, luteolin and wogonin on CYP1A1 enzyme. Molecular docking was used to study the binding of ligand to CYP1A1.RESULTS   After the S. barbata extract was transformed by intestinal bacteria, the content of cutellarein increased at the earliest stage and then decreased, the content of luteolin and wogonin were increased, the content of scutellarin, luteoloside and wogonoside were decreased. Additionally, there was no significant change in the content of Scutebarbatine A, B, and X. The inhibitory effect of S. barbata extract on CYP1A1 enzyme activity was increased after incubating with intestinal bacteria for 2, 4, 6 h, and this enhancement decreased after 12 h. The binding energy between scutellarin, luteolin, wogonin with human CYP1A1 were -6.33, -6.61 and -7.09 kcal/mol, respectively. The main interaction was the formation of π-π stacking between the ligand and Phe224 of CYP1A1.CONCLUSION   The flavonoids in S. barbata might be the main active substances that inhibit CYP1A1 enzyme activity.