The water-soluble extract of Ganoderma lucidum mycelia (WER) is prepared from a solid medium composed of bagasse and rice bran overgrown with Ganoderma lucidum mycelia. Recently, we reported that WER shows a blood glucose-lowering effect in maltose-loaded non-diabetic mice. Here, we investigated the efficacy of WER in type 2 diabetic state using KK-A y mice. Moreover, the food-drug interactions of WER with α-glucosidase inhibitors, voglibose or acarbose were examined using both in vitro and in vivo experiments. Methods: The glucose-lowering effects of oral administration in vivo of WER alone, or concomitant administration of WER with voglibose/acarbose on the elevation of blood glucose levels by sugar-tolerance tests were examined in KK-A y mice. The inhibitory effects on α-glucosidase in vitro were also evaluated. Results: Oral administration of WER (1 g/kg), which did not affect fasting blood glucose, significantly suppressed the hyperglycemia after loading of maltose (18% of decrease in AUC) compared to the water-administrated control mice. In vitro study showed that WER inhibited maltase in concentration-dependent manner. The inhibitory effects of lower concentrations of voglibose or acarbose on α-glucosidase activity were additively enhanced by the presence of WER, but those of higher concentrations were not affected. The glucose-lowering effect of voglibose (0.1 mg/kg) disappeared in maltose-loaded KK-A y mice when the drug was concomitantly administrated with WER (1 g/kg), whereas acarbose (16 mg/kg) with WER showed no significant change in its effect. Conclusion: These results demonstrated that WER shows the glucose-lowering effect in maltose-loaded KK-A y , which may be based on inhibition of the α-glucosidase activity. The present study suggests that concomitant intake of WER with voglibose may override the therapeutic effect of voglibose on postprandial hyperglycemia by food-drug interaction in diabetic state.

Objective: Ganoderma lucidum (Rei-shi) is widely used as an alternative medicine agent to promote health and longevity. The water-soluble extract from culture medium of Ganoderma lucidum mycelia (WER) is prepared from a solid medium composed of bagasse and rice bran overgrown for 3-4 months with Ganoderma lucidum mycelia. Design: In this study, we evaluate antioxidant activity of WER in vitro, and examined the effects of oral treatment of WER on oxidative stress in streptozotocin (STZ)-induced diabetic mice. Method: Male ICR mice were treated with STZ (150 mg/kg, i.p.) and were housed for a week for induction of experimental diabetic state. WER (1 g/kg daily) was orally administered for an additional 9 weeks, and the levels of blood glucose, oxidative stress in plasma, liver and kidney of the mice were assessed. Result: WER inhibited generation of superoxide anion and lipid peroxidation in concentration dependent manner in vitro. Oral administration of WER to diabetic mice significantly reduced the levels of blood glucose, hydroperoxides, triglyceride, ALT, and AST. Moreover, WER prevented the increase in lipid peroxide levels and the decrease in activity of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) in liver and kidney of diabetic mice. In addition, histochemical studies revealed that treatment of WER precluded the sinusoidal dilation in liver and expansion of mesangial matrix in kidney of diabetic mice. Normal mice treated with WER showed no change in any parameters studied. Conclusion: These data suggested that WER can act as an antioxidant in vivo, and show the antidiabetic effects by relieving diabetic hyperglycemia-induced oxidative stress.

The water-soluble extract of Ganoderma lucidum mycelia (WER) is prepared from a solid medium composed of bagasse and rice bran overgrown with Ganoderma lucidum mycelia. Recently, we have reported that WER had glucose-lowering effect in streptozotosin-induced diabetic mice, an animal model of type 1 diabetes. Here, we investigated whether long-term treatment with WER affects hyperglycemia and insulin resistance in KK-A y mice, a type 2 diabetic animal model with obesity. Methods: Female KK-A y mice were given free access to water and high-fat food containing 0.5% WER for 8 weeks, with blood glucose and plasma insulin levels assessed every week. At the end of the experimental period, insulin tolerance test (ITT) was performed, and plasma levels of triglyceride, total cholesterol, HDL-cholesterol, AST, ALT and adiponectin were measured. Furthermore, expression of GLUT4 in skeletal muscle cell membrane and adipocytes was also determined by immunostaining and Western blot analysis. Results: The mice with high-fat ingestion showed a gradual increase in levels of blood glucose and body weight. In the WERtreated mice, the blood glucose level was significantly suppressed after 2 weeks of treatment. WER also reduced plasma levels of ALT and insulin, but did not affect the other parameters. Additionally, ITT revealed that WER improved insulin sensitivity. Moreover, expression of GLUT4 in the plasma membrane of skeletal muscle cells and adipocytes of the WER-treated mice was increased. Conclusion: These results indicate that WER has a glucose-lowering effect in type 2 diabetic mice. WER also improved hyperinsulinemia and insulin sensitivity, which may derive from enhancement of glucose uptake through GLUT4 of skeletal muscle cells and adipocytes.