ABSTRACT
<b>Objective</b>: <i>Lentinus edodes</i> (Shiitake) is a very popular mushroom in Asian cuisine. The water-soluble extract from culture medium of <i>Lentinus edodes</i> mycelia (LEM), which is commercially available as a nutritional supplement, is prepared by hot-water treatment from a solid medium composed of bagasse and defatted-rice bran overgrown for about 4 months with its mycelia. LEM was previously reported to have antioxidant activity and to suppress various oxidative damages. In this study, the neuroprotective effects of 2-week intake of LEM on cerebral ischemic damage induced by hypoxia/ischemia (H/I) followed by reoxygenation in mice were examined.<br> <b>Method</b>: Male C57BL/6J mice were divided into three groups, fed for two weeks with the control laboratory powder chow, 0.5% LEM-contained chow, or 1% LEM-contained chow, respectively. Cerebral ischemic damage was induced in the mice by H/I (i.e., unilateral ligation of the carotid artery and exposure of 8%O<sub>2</sub> for 30 min). Twenty-four hours after H/I, total plasma oxidative stress, neurological deficits, cerebral infarction volume were evaluated in each group. Furthermore, the number of apoptotic cells in ischemic penumbra, the hippocampal CA1 and CA2, and the somatosensory area of the cortex, were analyzed by TUNEL staining and cleaved caspase-3 immunostaining.<br> <b>Results</b>: The infarct area assessed 24-h after H/I was extended to the corpus striatum and cortex in the control mice. Treatment of LEM dose dependently improved plasma oxidative stress, neurological deficits, and cerebral infarction volume. Moreover, LEM decreased the levels of dihydroethidium activity as an index of super oxide production and the number of apoptotic cells in ischemic penumbra.<br> <b>Conclusion</b>: These results show that chronic intake of LEM relieves the hypoxia-induced cerebral ischemic injury, which may be attributed to the antioxidant effects of LEM.<br>
ABSTRACT
<b>Objective:</b> The water-soluble extract of <i>Ganoderma lucidum</i> mycelia (WER) is prepared from a solid medium composed of bagasse and rice bran overgrown with<i> Ganoderma lucidum</i> 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<sup>y</sup> mice. Moreover, the food-drug interactions of WER with α-glucosidase inhibitors, voglibose or acarbose were examined using both <i>in vitro</i> and <i>in vivo </i>experiments.<br> <b>Methods:</b> The glucose-lowering effects of oral administration <i>in vivo</i> 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<sup>y</sup> mice. The inhibitory effects on α-glucosidase <i>in vitro</i> were also evaluated.<br> <b>Results:</b> 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. <i>In vitro</i> 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<sup>y</sup> 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.<br> <b>Conclusion:</b> These results demonstrated that WER shows the glucose-lowering effect in maltose-loaded KK-A<sup>y</sup>, 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.<br>
ABSTRACT
<i>Objective</i>: The water-soluble extract of <i>Ganoderma lucidum</i> mycelia (WER) is prepared from a solid medium composed of bagasse and rice bran overgrown with <i>Ganoderma lucidum</i> 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<sup>y</sup> mice, a type 2 diabetic animal model with obesity.<br> <i>Methods</i>: Female KK-A<sup>y</sup> 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.<br> <i>Results</i>: The mice with high-fat ingestion showed a gradual increase in levels of blood glucose and body weight. In the WER-treated 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.<br> <i>Conclusion</i>: 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.<br>