Anti-diabetic effects of mulberry (Morus alba L.) branches and oxyresveratrol in streptozotocin-induced diabetic mice

Abstract

Despite with accumulating evidences on the anti-diabetic effects of mulberry branch (MB), the major active component for the activity has not been known. Oral administration of MB ethanol (EtOH) extracts [0.5 or 1 g/kg body weight (BW)] once a day for 22 days to streptozotocin-induced diabetic ICR mouse significantly reduced fasting blood and plasma glucose level in a dose dependent manner compared to those of the diabetic control. Administration of oxyresveratrol [ORT, 0.6 g/kg BW], a major compound of MB EtOH extracts, to diabetic ICR mouse also significantly reduced fasting plasma glucose level. Further, ORT increased hepatic glucose transporter 2 transcription and glycogen content. Plasma insulin concentration and intestinal disaccharidase activity were not different between diabetic control and ORT groups. This suggests that ORT reduced plasma glucose by stimulating hepatic glucose uptake and glycogen storage. MB EtOH extracts and ORT could be potential adjunct therapies for diabetes management.

Keywords: Diabetes; Mouse; Mulberry branch; Oxyresveratrol; Streptozotocin.

Fig. 1

HPLC chromatograms of two standards, mulberroside A (MSA) and oxyresveratrol (ORT) (A), and the EtOH extract of mulberry branch (MB) (B). 1: Mulberroside A (MSA), 2: oxyresveratrol (ORT)

Fig. 2

Schematic representation of the experiments in T1DM animal model. (A) Experiment I; after 1 week of adaptation, male ICR mice were injected 5 times with STZ (40 mg/kg/day). Experimental supplement was orally administrated to mice in each group once a day for 22 days after the last injection of STZ. STZ, streptozotocin; MBE, mulberry branch EtOH extract, (B) experiment II; After 1 week of adaptation, male ICR mice were injected 5 times with STZ (40 mg/kg/day). Experimental supplement was orally administrated to mice in each group once a day for 22 days after the last injection of STZ. STZ streptozotocin, ORT oxyresveratrol, Met metformin

Fig. 3

Hypoglycemic effects of MB EtOH extracts. In STZ-induced diabetic ICR mouse, EtOH extracts of MB (0.5 or 1 g/kg BW) were orally administered for 22 days. After 10 days of oral administration, fasting blood glucose (FBG) (A) was measured from mouse tail vein. Concentration of plasma glucose (B) was measured after euthanization. Values are presented as the mean ± SE. Means with different letters are significantly different at p < 0.05 using Duncan’s multiple range test. NS, not significant; NC, normal control; DC, diabetes control; MBE0.5, mulberry branch EtOH extract 0.5 g/kg BW; MBE1, mulberry branch EtOH extract 1 g/kg BW

Fig. 4

Effect of ORT on the level of plasma glucose and insulin. In STZ-induced diabetic ICR mouse, ORT (0.6 g/kg BW) and Met (0.6 g/kg BW) were orally administered for 22 days. After 10 days of oral administration, fasting blood glucose (FBG) (A) was measured from mouse tail vein. Concentration of plasma glucose (B) and insulin (C) was measured after euthanization. Values are presented as the mean ± SE. Means with different letters are significantly different at p < 0.05 using Duncan’s multiple range test. NS not significant, NC normal control, DC diabetes control, DORT diabetes + oxyresveratrol; DMet diabetes + metformin

Fig. 5

Effect of ORT on intestinal disaccharidase activity. Lactase (A), sucrase (B), and maltase (C) activity were measured at the proximal region of the small intestine. Values are presented as the mean ± SE. Means with different letters are significantly different at p < 0.05 using Duncan’s multiple range test. NS not significant, NC normal control, DC diabetes control, DORT diabetes + oxyresveratrol, DMet diabetes + metformin

Fig. 6

Effect of ORT on GLUT2 expression and glycogen contents in the liver of diabetic mouse. In STZ-induced diabetic ICR mouse, ORT (0.6 g/kg BW) and Met (0.6 g/kg BW) were orally administered for 22 days. After euthanization, expression of glucose transporter 2 (GLUT2) mRNA in the liver (A) was measured by qRT-PCR. Concentration of liver glycogen (B) was measured. Values are presented as the mean ± SE. Means with different letters are significantly different at p < 0.05 using Duncan’s multiple range test. NS not significant, NC normal control, DC diabetes control, DORT diabetes + oxyresveratrol, DMet diabetes + metformin