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There is evidence that inflammatory processes are involved in the development and/or progression of diabetic nephropathy. However, effective treatment for inflammation in the kidneys of diabetic is practically unknown. The rhizomes of Picrorhiza scrophulariiflora (PS) are a traditional medication long used to treat inflammatory diseases. The aim of the present study was to test the hypothesis that the ethanol extract of PS (EPS) may reduce inflammation in patients with diabetic kidneys. Streptozotocin-induced diabetic rats were randomly assigned to two groups treated with a gavage of either EPS or vehicle. A group of non-diabetic control rats was treated concurrently. Compared with vehicle-treated diabetic rats, EPS-treated animals displayed a significant decrease in renal macrophage infiltration and overexpression of chemokine (C-C motif) ligand 2 (CCL2) and TGFB1. This was associated with attenuation of the structural and functional abnormalities of early diabetic nephropathy, such as glomerular hypertrophy, mesangial expansion, and albuminuria. Administration of EPS significantly reduced NADPH oxidase-dependent superoxide generation and decreased expression of malondialdehyde and advanced oxidation protein products in diabetic kidney. These data suggest that EPS might improve diabetic nephropathy, probably through inhibition of redox-sensitive inflammation.
Shanghai Key Laboratory of Endocrine Tumor, Division of Endocrinology and Metabolism, Shanghai Jiao-Tong University School of Medicine, Shanghai Institute of Endocrinology and Metabolism, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, 197 Rui-Jin 2nd Road, Shanghai 200025, People's Republic of China
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Shanghai Key Laboratory of Endocrine Tumor, Division of Endocrinology and Metabolism, Shanghai Jiao-Tong University School of Medicine, Shanghai Institute of Endocrinology and Metabolism, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, 197 Rui-Jin 2nd Road, Shanghai 200025, People's Republic of China
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Shanghai Key Laboratory of Endocrine Tumor, Division of Endocrinology and Metabolism, Shanghai Jiao-Tong University School of Medicine, Shanghai Institute of Endocrinology and Metabolism, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, 197 Rui-Jin 2nd Road, Shanghai 200025, People's Republic of China
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Shanghai Key Laboratory of Endocrine Tumor, Division of Endocrinology and Metabolism, Shanghai Jiao-Tong University School of Medicine, Shanghai Institute of Endocrinology and Metabolism, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, 197 Rui-Jin 2nd Road, Shanghai 200025, People's Republic of China
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Shanghai Key Laboratory of Endocrine Tumor, Division of Endocrinology and Metabolism, Shanghai Jiao-Tong University School of Medicine, Shanghai Institute of Endocrinology and Metabolism, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, 197 Rui-Jin 2nd Road, Shanghai 200025, People's Republic of China
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Shanghai Key Laboratory of Endocrine Tumor, Division of Endocrinology and Metabolism, Shanghai Jiao-Tong University School of Medicine, Shanghai Institute of Endocrinology and Metabolism, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, 197 Rui-Jin 2nd Road, Shanghai 200025, People's Republic of China
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Shanghai Key Laboratory of Endocrine Tumor, Division of Endocrinology and Metabolism, Shanghai Jiao-Tong University School of Medicine, Shanghai Institute of Endocrinology and Metabolism, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, 197 Rui-Jin 2nd Road, Shanghai 200025, People's Republic of China
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Genipin, a compound derived from Gardenia jasminoides Ellis fruits, has been used over the years in traditional Chinese medicine to treat symptoms of type 2 diabetes. However, the molecular basis for its antidiabetic effect has not been fully revealed. In this study, we investigated the effects of genipin on glucose uptake and signaling pathways in C2C12 myotubes. Our study demonstrates that genipin stimulated glucose uptake in a time- and dose-dependent manner. The maximal effect was achieved at 2 h with a concentration of 10 μM. In myotubes, genipin promoted glucose transporter 4 (GLUT4) translocation to the cell surface, which was observed by analyzing their distribution in subcellular membrane fraction, and increased the phosphorylation of insulin receptor substrate-1 (IRS-1), AKT, and GSK3β. Meanwhile, genipin increased ATP levels, closed KATP channels, and then increased the concentration of calcium in the cytoplasm in C2C12 myotubes. Genipin-stimulated glucose uptake could be blocked by both the PI3-K inhibitor wortmannin and calcium chelator EGTA. Moreover, genipin increases the level of reactive oxygen species and ATP in C2C12 myotubes. These results suggest that genipin activates IRS-1, PI3-K, and downstream signaling pathway and increases concentrations of calcium, resulting in GLUT4 translocation and glucose uptake increase in C2C12 myotubes.
