Scopoletin Improves Glucose Homeostasis in the High-Fructose High-Fat Diet-Induced Diabetes Model in Wistar Rats

Antihyperglycemic action of scopoletin needs to be validated before considering it for clinical trials. The present study explored antihyperglycemic action of scopoletin in high-fructose high-fat diet (HFHFD)-induced diabetes in rats. The animal study was performed using 48 rats, 6 in each group. HFHFD was administered for model induction for 74 days. Rats in Group I (normal control [NC]) and group II (experimental control [EC]) received normal saline and HFHFD, respectively, throughout the study. Groups III, IV, V, and VI received oral scopoletin (1 mg/kg [low dose, LD], 5 mg/kg [medium dose, MD], 10 mg/kg [high dose, HD]), and metformin (250 mg/kg; positive control [PC] for efficacy), respectively, once daily from day 60 to 74, in addition to HFHFD. Group VII (10 mg/kg oral scopoletin safety group) and VIII (0.1 mg/kg oral warfarin; PC for safety) were separately used for bleeding time-clotting time (BTCT) assessment on days 60, 68, and 74. Groups I, VII, and VIII rats were studied for safety assessment. Later, animals were sacrificed for histological examination. Scopoletin-treated groups showed a significant decline in glucose levels, especially in the MD (5.18 +/- 0.12) and HD group (5.271 +/- 0.11) in comparison to the EC (6.37 +/- 0.05) on day 74 (P < .05). Two weeks after scopoletin treatment, beta-cell function significantly improved (53.073 +/- 4.67) in the MD group versus 29.323 +/- 8.505 in the NC group (P < .05). A statistically significant difference was observed when the MD group (53.07 +/- 4.67) was compared to the metformin-treated group (24.80 +/- 3.24; P < .05). The safety assessment in the form of BTCT findings did not observe a difference among groups I, VII, and VIII (P > .05). The study showed that scopoletin dose-independently reversed insulin resistance. Consequently, scopoletin can be a potential candidate for antidiabetic drug development.