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OBJECTIVE To study the hypoglycemic effects of columbin and its effects on catalytic activities as well as gene expression of hepatic cytochrome P450 (CYP450) isozymes in experimental type 2 diabetic rats.METHODS High-fat diet and streptozotocin-induced (HFD-STZ) type 2 diabetic rats were equally randomized into 3 groups: a model control group, a low dose columbin group (25 mg·kg-1 ·d-1 , ig) and a high dose columbin group (50 mg·kg-1 ·d-1 , ig).The animals were treated for4 weeks.Fasting blood glucose concentration, serum insulin, total cholesterol (TC), triglycerides (TG), free fatty acid (FFA), body weights, insulin sensitivity index (ISI) and oral glucose tolerance test (OGTT) were determined to evaluate hypoglycemic effects.At the end of treatment, the rats were sacrificed about 2 h later after the last dose.Livers were harvested and microsomes were prepared and analyzed for enzyme activities.Total RNA was also isolated and the mRNA levels of various CYPs were determined by quantitative RT-PCR with Taqman MGB probes.RESULTS A significant reduction of fasting blood glucose were observed in the low dose group (P < 0.05) and high dose group (P < 0.01) compared with the model control group; Columbin could remarkably improve the levels of ISI (P < 0.05) compared with untreated group; Furthermore, columbin improved oral glucose tolerance and reduced TC, TG levels and FFA.However, columbin had no significant effects on body weight and serum insulin.The catalytic activities and mRNA expression levels of CYP1A1, CYP1A2, and CYP2B1 in model control group were raised in different degree; Columbin showed significant inhibition effects on their activities and mRNA expression levels in experimental type 2 diabetic rats, which showed good dosage effect relationship.The catalytic activities and mRNA levels of CYP2B1, CYP2C11, and CYP2E1 in model control group were decrease compared to normal control group; while columbin increased the catalytic activities of these CYP450s and positively modulated their mRNA transcriptional levels.Columbin didnt significantly impact the activity and mRNA transcriptional level of CYP2D1 in type 2 diabetes mellitus rats.CONCLUSION Columbin exhibits hypoglycemic activity and reduces insulin resistance in type 2 diabetes rats.It also reversed the changes of CYP450 isozymes through the regulation at transcriptional level, which make the drug metabolism in the liver in type 2 diabetes rats tend to be normal.