CAG ameliorates diabetes-related metabolic syndromes in ZDF diabetes rat
ZDF diabetes rat, a well-known model mimicking the characteristics of T2DM populations, was applied to determine the anti-diabetes effects ofCAG in vivo . The related indexes, including body weight, levels of glucose, HbA1c, triglyceride, cholesterol, LDL-c, and HDL-c in the ZDF rats treated with CAG for five weeks, were determined. As shown in Figure 3A, Dapagliflozin decreased plasma glucose after one week of treatment, and this strong glucose-decreasing effect did not maintain to 5 weeks as observed by a slight increase in plasma glucose level in week 2~5. Compared with Dapagliflozin, CAG could reduce blood glucose levels with a concentration-dependent mode. Either the hypoglycemic effect or the later increase of glucose level is not as apparent as Dapagliflozin. The OGTT assay further confirmed that CAG had a mild hypoglycemic effect on plasma glucose in mice (Figure 3B and 3C).
In clinical, diabetes populations are accompanied by several metabolic syndromes (MetS), bodyweight decrease, and tissue breakdown, especially at the late stage. Thus, we evaluated the effect of CAG on bodyweight and observed a progressive decrease in body weight in the vehicle group, while Dapagliflozin and CAG efficiently reversed this decrease (Figure 3D). Consistent with the plasma glucose-decreasing effect in KM mice, CAG dose-dependently decreased serum glucose and HbA1c levels as well as the insulin excretion level, whereas Dapagliflozin showed no major effect on insulin level in rats (Figure 3E). Especially for another important clinical diagnosis index for diabetes, glycated hemoglobin (HbA1c)(Rodbard et al., 2007),CAG showed significant decreasing effect similar to Dapagliflozin (Figure 3E). Meanwhile, CAG could also efficiently decrease plasma triglyceride, low-density lipoprotein cholesterol (LDL-c) and reverse the progressive degeneration of ratio HDL-c/LDL-c in ZDF rats (Figure 3F-3I).
CAG inhibits