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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.

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Chronic treatment of rats with haloperidol decanoate (30 mg/kg and 100 mg/kg IM every 4 weeks for 52 weeks) increased [3H] SCH 23390 binding in striatal membranes by 25% and 50% and in frontal cortical membranes by 56% and 125% in 30 and 100 mg/kg haloperidol treatment groups, respectively. These increases in [3H] SCH 23390 binding to the membranes were restored to control levels after ceruletide treatment (100 micrograms/kg IP twice a day for 5 days). [3H] Spiperone binding to the rat striatal and cortical membranes also increased after chronic haloperidol treatment (by 66% and 99% in striatal membranes and by 27% and 62% in cortical membranes in the 30 and 100 mg/kg haloperidol treatment groups, respectively). Administration of ceruletide to haloperidol-treated rats reduced the increased [3H] spiperone binding to the cortical membranes toward the control level, but ceruletide was not effective in reducing the haloperidol-induced increase of [3H] spiperone binding to the striatal membranes. Activation of adenylate cyclase by dopamine (1 microM or 100 microM) or Gpp(NH)p (1 microM) was reduced in striatal and cortical membranes from haloperidol-treated rats. Ceruletide restored the lowered level of dopamine-stimulated or Gpp(NH)p-stimulated adenylate cyclase activity in the membranes from haloperidol-treated rats to control levels.(ABSTRACT TRUNCATED AT 250 WORDS)

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.