Investigation of the Effects of Difluorinated Curcumin on Glycemic Indices in Streptozotocin-Induced Diabetic Rats.

BACKGROUND: Curcumin is an antioxidant agent that improves glycemia in animal models of diabetes. Clinically curcumin use is limited due to poor solubility, weak absorption, and low bioavailability; therefore, this study to investigate the effects of curcumin's analog, difluorinated curcumin (CDF), on fasting blood glucose (FBG), oral glucose tolerance test (OGTT), and insulin tolerance test (ITT), in streptozotocin (STZ)-induced diabetic rats was undertaken. METHODS: STZ-induced diabetes rats were randomly assigned to six groups (7 rats per group). They were treated daily by oral gavage with curcumin (200 and 100 mg/kg/day), CDF (200 and 100 mg/kg/day), and metformin (200 mg/kg/day) as a positive control group, for 4 weeks. Two diabetic control (DC) and normal control (NC) groups (non-diabetic rats) received normal saline and citrate buffer, respectively. FBG was measured at the beginning and end of the treatment (Day 0 and week 4) and OGTT and ITT were performed to determine glucose tolerance and insulin sensitivity. RESULTS: Cur100, CDF 100, and CDF200 significantly decreased FBG levels after 4 weeks oral administration by -34% (-150 mg/dL ± 70, p = 0.02), -36% (123 mg/dL ±67, p < 0.04), and - 40% (-189 mg/dL ± 91, p = 0.03), respectively. Glucose sensitivity by OGTT showed a significant improvement in glucose tolerance ability in all treated groups compared with DC group. ITT demonstrated that insulin response improved significantly in Cur100 and CDF 200 groups. CONCLUSION: Overall, CDF improved glucose tolerance and insulin sensitivity, while reducing FBG compared to curcumin, suggesting that curcumin analogs may have therapeutic utility in diabetes.