[Effects of Shuganning Injection on enzymatic activities of cytochrome P450 and its interaction with bicyclol]

This study investigated the effects of Shuganning Injection(SGN) on the enzymatic activities of cytochrome P450(CYP450) and its interaction with bicyclol(BIC). In vitro assessments were performed utilizing the Cocktail probe drug method in combination with a human liver microsome incubation system. UPLC-MS/MS analysis revealed that SGN inhibited the enzymatic activities of CYP1A2, CYP2D6, CYP2C9, CYP2C19, CYP3A4, and CYP2E1 in a concentration-dependent manner. In vivo experiments demonstrated that SGN significantly altered the pharmacokinetic parameters of caffeine, dextromethorphan, midazolam, and omeprazole in rats, primarily characterized by a marked increase in the area under the curve(AUC)(P<0.05) and a significant decrease in clearance(CL)(P<0.05). These findings suggest that SGN may inhibit the activities of CYP1A2, CYP2C19, CYP2D4, and CYP3A2. After co-administration with BIC, the exposure level(AUC_(0-t)) of BIC was significantly increased, while its CL significantly decreased. Further analysis using real-time quantitative PCR and Western blot confirmed that SGN significantly downregulated the mRNA and protein expression of CYP2C19 and CYP3A2 in rat liver. The results indicate that SGN can inhibit the activities of CYP1A2, CYP2C19, CYP2D4, and CYP3A2 in rats. By inhibiting CYP2C19 and CYP3A2, SGN slowed down the metabolic clearance of BIC, leading to elevated plasma drug concentrations. These findings suggest a potential risk of increased drug exposure when SGN is used in combination with BIC in clinical practice.