Molecular mechanism of alcoholic extract from medicinal mushroom Inonotus obliquus improve early-stage nephritic dysfunction and late-stage renal fibrosis of type 2 diabetic mice-derived

• Main Authors: Wen-Chun Yu, 余文鈞
• Other Authors: Jiunn-Jye CHuu
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/16841293051496925703

碩士 === 南台科技大學 === 生物科技系 === 97 === In the study, we are looking for construct many kinds of non-genetic deficient DM 2 animal models, which closely simulates the metabolic abnormalities of the human disease and is also cost-effective compared with the genetic models currently available. It is suggested that disease models prior to serving with renal fibrosis, which may be used for studies on type 2 diabetic nephropathy animal models. The experimental mice were orally administrated high-fat diet (HFD) for consecutive 8 weeks, following by 7 consecutive days of streptozotocin (STZ, 50mg/Kg, ip) plus nicotinamide (NA, 200mg/Kg, ip), eventually which almost caused hyperglycemia and hyperinsulina occurred on HFD-controlled C57BL/6 mice (fasting blood glucose over 150 mg/dl, and ACR over 2 g/mg, alternatively). Inonotus obliquus is a white rot fungus, which belongs to the family Hymenochaetaceae of Basidiomycetes. Recently, there have been reports hat melanin complexes from sclerotia contain strong anti-oxidants. In our study, we detect the effect of hyperglycemia via the toxicity of diabetic nephropathy-prone, which produced by hyperglycemia from the damage of LLC-PK1 renal tubular cells. It suggested that the effectiveness of Inonotus obliquus needed to be conducted for the treatment of type 2 diabetic nephropathy. The preparation of experimental animals started with high fat diet (HFD) administration for 8 weeks followed by intraperitoneal injection of streptozotocin (STZ 50 mg/Kg) and nicotinamide (NA, 200 mg/kg). Once fasting hyperglycemia (over 150mg/dl, fasting period), hyperinsulinemia (10 unit), and positive microalbuminuria (ACR, 2 mg/g Creatinine) occured gradually on HFD-controlled C57BL/6 mice, the candidates were divided into 4 groups, (1) saline, (2) Innonotus oblique (IO), (3) rosiglitazone (R.S), and (4) Cordyceps sinensis (CS). Treatment with oral dosing ethanol extracts of Innonotus oblique and Cordyceps sinensis of 1000 mg/kg/day and 300 mg/kg/day for 8 weeks. The result MTT assay will claim the glucotoxicity, respectively in renal proximal tubular cell line（LLC-PK1） in vitro in a concentration-dependent AGE. We found that the Innonotus oblique also improve the glucose tolerance and insulin resistance with increasing TGF-β and NFκB expression kindey of high fat diet-induced diabetic nephropathy mice by western blotting. Immunohistochemical evaluation showed weak TGF-β staining in the glomeruli of native and I.O group, but in the control group the signal was markedly stronger. In conclusion, our data demonstrated that the alcoholic extract from Inonotus obliquus treatment has shown a potential anti-hyperglycemic effect, and significantly inhibited the early stage and late-stage renal fibrosis of glucolipotoxicity-induced nephrofibrosis in high fat diet-induced diabetic nephropathy mice.