Background: Reishi (Ganoderma lucidum) is a well-known and popular edible mushroom eaten as vegetables all over the world. It has been used as alternative medicine for long years in China, Korea, Japan, Malaysia, and in eastern Russia. It is reported to exhibit a number of medicinal properties including antitumor, antioxidant, immunomodulating, anti-inflammatory, hepatoprotective, and hypoglycemic activities due to the presence of bioactive polysaccharide. Glucocorticoids, prescribed for the treatment of arthritis to protect inflammation and reduce pain, can induce hyperglycemia or aggravate the hyperglycemic condition reaching to very high glucose levels in diabetic patients. However, no report has been published for its activity on glucocorticoid-induced diabetes. Objective: To investigate the effect of Ganoderma lucidum on alloxan- and glucocorticoid- induced diabetes in Long-Evans rats. Methods: Alloxan monohydrate (150 mg/kg) was intraperitoneally administered to Long-Evans rats as a single dose. The same volume of normal saline was injected to control rats. Three days after alloxan injection, rats with plasma glucose levels higher than 12 mmoL /L were considered as diabetic and they were included in the study. Reishi mushroom was collected from the Mushroom Development Institute, Ministry of Agriculture, Savar, Dhaka, Bangladesh, where it was identified by a Taxonomist. Petroleum ether extract (PEE) Methanol extract (ME) were prepared by maceration and distillation techniques. The extracts were orally administered once in a day at doses of 200, 400, 600 and 800 mg/kg, respectively for 7 days. Metformin (150 mg/kg) was orally administered as a standard antidiabetic drug. Glucose levels were measured at 0 and 7th days of treatment. The rats were allowed to rest for 1 week without treatment. The animals were again injected with dexamethasone (2 mg/kg) through intra-muscular route for 3 days and glucose levels were monitored regularly. Rats were then further treated with PEE and ME and metformin for another 7 days and glucose levels were determined at 0 and 7th days of treatment. Results: The PEE and ME of Reishi mushroom dose-dependently reduced the plasma glucose levels in alloxan-and steroid-induced fasting diabetic rats. The maximum reduction of fasting plasma glucose levels observed by PEE (800 mg/kg) and ME (800 mg/kg) were 55.57% and 36.01% in alloxan-induced and 51.41% and 32.02% in steroid-induced diabetic rats, respectively. Whereas, metformin (150 mg/kg) resulted in the diminution of fasting blood glucose levels by 60.02 and 51.12% in the alloxan- induced and steroid-induced diabetic rats, respectively. Both the PEE (800 mg/kg) and ME (800 mg/kg) significantly augmented plasma insulin levels (***P < 0.001 and **P < 0.01) and reduced HbA1c (**P < 0.01 and *P < 0.05) in alloxan-and steroid-induced diabetic rats. Besides, treatment of diabetic rats with PEE (800 mg/kg) and ME (800 mg/kg) controlled the 2-h post prandial elevated glucose levels in blood plasma. The same dose of the extracts also significantly reduced the levels of total cholesterol (TC) (***P < 0.001 and ***P < 0.01), triglyceride (TG) (***P < 0.001 and **P < 0.01) and low-density lipoprotein-cholesterol (LDL-c) (***P < 0.001 and ***P < 0.001), as well as increased the level of high density lipoprotein cholesterol (HDL-c) (**P < 0.01 and **P < 0.01, respectively). Conclusion: Our study demonstrated that edible mushrooms-Reishi has antihyperglycemic, insulin-sensitivity, and hyperlipidaemic activity against both alloxan- and corticosteroid-induced diabetes rats. The bioactive chemicals responsible for those activities are most probably the polysaccharides available in the mushroom. Thus, usage of Reishi mushrooms as vegetables or as extract will be beneficial for the management of diabetes.Keywords: Antihyperglycemic, antidiabetic, insulin-sensitizer, anti-hyperlipidemic, Gano mushroom, Reishi mushroom, Ganoderma lucidum, alloxan-induced diabetes, Steroid induced diabetes, Glycated haemolgobin (HbA1c), Oral glucose tolerance test (OGTT), Hyperlipidemia
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