The Intestinal Target And Mechanism Of Berberine On Diabetes Mellitus

The Chinese Goldthread Rhizome has been used in the Traditional Chinese Medicine as an important ingredient of many formulas for the treatment of diabetes mellitus. Berberine, the main effective composition of Chinese Goldthread Rhizome, is also effective in treating diabetes in today’s clinical practice of Traditional Chinese Medicine. The aim of the study is to evaluate the hypoglycemic activity of berberine which treating acutely on the postprandial blood glucose, and to explore the mechanism of this activity.Methods:One-dose preprandial intragastric administrations of berberine were given to normal animals (mice, rats and dogs), and the postprandial blood glucose concentration curves were measured. Serum insulin enzyme linked immunosorbent assay (ELISA) was performed in rats. The euglycemic clamp test was performed to evaluate the effect of one-dose berberine intragastric administration on the blood glucose transformation and utilization rate in rats. In the Caco-2 cell monolayer test, the changes of glucose concentration on the apical and basolateral sides were measured when the maltose solution containing berberine was added to the apical side. The inhibition ratio of berberine against a-glucosidase was measured in vitro. The effect of berberine on the fluorescence emission spectrums of a-glucosidase was studied. Berberine and a certain quantity maltose were injected into the mouse ansa intestinalis and the maltose remained in it was measured at some given time points.Results:One-dose preprandial intragastric administration of berberine decreased the rise of post-maltose blood glucose in mice, rats and dogs; did not affect postprandial blood glucose after glucose meal. One-dose intragastric administration of berberine did not affect the insulin level in normal rats. The result of euglycemic clamp test showed that one-dose intragastric administration of berberine had no effect on the blood glucose transformation and utilization rate in rats. Berberine added to the maltose solution on the apical side of Caco-2 cell monolayer reduced the glucose concentration on the apical side. Glucose in basolateral side of all groups cannot be detected. Berberine inhibited the activity of a-glucosidase in vitro. Berberine significantly and concentration dependently quenched the fluorescence emission spectrum of a-glucosidase. Berberine increased the maltose remained in the mouse ansa intestinalis after a certain quantity maltose was injected in it.Conclusion:our findings suggest an additional mechanism of the hypoglycemic activity of berberine by demonstrating its ability to acutely inhibit the α-glucosidase, and support the traditional use of berberine and Chinese Goldthread Rhizome for the treatment of diabetes mellitus.