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Extract of Rhizoma Polygonum cuspidatum reduces early renal podocyte injury in streptozotocin‑induced diabetic rats and its active compound emodin inhibits methylglyoxal‑mediated glycation of proteins.

Sohn E, Kim J, Kim CS, Jo K, Kim JS - Mol Med Rep (2015)

Bottom Line: However, treatment with PCE for 16 weeks restored protein levels to normal, and reduced podocyte loss and apoptosis.Levels of caspase‑3 and MGO expression, as well as oxidative stress were ameliorated by PCE treatment.In addition, emodin, a biologically active ingredient of PCE, exerted an MGO scavenging effect and inhibited MGO‑derived advanced glycation end‑product formation.

View Article: PubMed Central - PubMed

Affiliation: Korean Medicine Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 305‑811, Republic of Korea.

ABSTRACT
Podocyte injury contributes to renal damage and, eventually, to the occurrence of proteinuria in diabetic nephropathy. The aim of the present study was to investigate the effect of an ethanol extract from Rhizoma Polygonum cuspidatum (P. cuspidatum) on proteinuria and podocyte injury, and elucidate the underlying mechanism for streptozotocin (STZ)‑induced diabetic nephropathy. The protective effects of P. cuspidatum extract (PCE) on renal podocytes in STZ‑induced diabetic rats were also investigated. PCE (100 or 350 mg/kg/day) was administered to STZ‑induced diabetic rats for 16 weeks, and blood glucose levels, body weight and proteinuria were measured. A double labeling technique with the terminal deoxynucleotidyl transferase dUTP nick end labeling assay was performed and synaptopodin expression was observed. In addition, cleaved caspase‑3, methylglyoxal (MGO) and 8‑hydroxydeoxyguanosine (8‑OHdG) expression levels were measured. STZ‑induced diabetic rats developed hyperglycemia and proteinuria. Increased apoptosis of the podocytes and increased cleaved caspase‑3, MGO and 8‑OHdG expression levels, as well as decreased synaptopodin expression were detected in the glomeruli of STZ‑induced diabetic rats. However, treatment with PCE for 16 weeks restored protein levels to normal, and reduced podocyte loss and apoptosis. Levels of caspase‑3 and MGO expression, as well as oxidative stress were ameliorated by PCE treatment. In addition, emodin, a biologically active ingredient of PCE, exerted an MGO scavenging effect and inhibited MGO‑derived advanced glycation end‑product formation. These findings indicate that PCE may be administered to prevent proteinuria and podocyte loss in STZ‑induced diabetic rats partly by inhibiting podocyte apoptosis and cleaved caspase‑3 expression, and by restoring the balance of oxidative stress and MGO expression.

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Effect of PCE on podocyte loss. Representative histology sections from the NOR, DM, PCE-100 and PCE-350 groups (magnification, ×400): (A) Synaptopodin and (B) WT-1 staining of the glomeruli. Morphometric analysis of (C) synaptopodin and (D) WT-1 in the renal cortex of rats from each group. All data are expressed as the mean ± standard error of the mean (n=8). *P<0.01 vs. NOR group; #P<0.01 vs. DM group. NOR, normal rat; DM, streptozotocin-induced diabetic rat; PCE-100, DM treated with 100 mg/kg PCE; PCE-350, DM treated with 350 mg/kg PCE; PCE, Polygonum cuspidatum extract; WT-1, Wilms Tumor 1.
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f1-mmr-12-04-5837: Effect of PCE on podocyte loss. Representative histology sections from the NOR, DM, PCE-100 and PCE-350 groups (magnification, ×400): (A) Synaptopodin and (B) WT-1 staining of the glomeruli. Morphometric analysis of (C) synaptopodin and (D) WT-1 in the renal cortex of rats from each group. All data are expressed as the mean ± standard error of the mean (n=8). *P<0.01 vs. NOR group; #P<0.01 vs. DM group. NOR, normal rat; DM, streptozotocin-induced diabetic rat; PCE-100, DM treated with 100 mg/kg PCE; PCE-350, DM treated with 350 mg/kg PCE; PCE, Polygonum cuspidatum extract; WT-1, Wilms Tumor 1.

Mentions: The podocyte content was determined by counting the cells that were stained with synaptopodin and WT-1, the podocyte marker (Fig. 1A and B). The number of synaptopodin- and WT-1-positive cells in the STZ-induced diabetic rat group was reduced compared with that of the normal control rats (P<0.01). Treatment with PCE markedly increased the podocyte content in the renal glomeruli in a dose-dependent manner (P<0.01; Fig. 1B and C).


Extract of Rhizoma Polygonum cuspidatum reduces early renal podocyte injury in streptozotocin‑induced diabetic rats and its active compound emodin inhibits methylglyoxal‑mediated glycation of proteins.

Sohn E, Kim J, Kim CS, Jo K, Kim JS - Mol Med Rep (2015)

Effect of PCE on podocyte loss. Representative histology sections from the NOR, DM, PCE-100 and PCE-350 groups (magnification, ×400): (A) Synaptopodin and (B) WT-1 staining of the glomeruli. Morphometric analysis of (C) synaptopodin and (D) WT-1 in the renal cortex of rats from each group. All data are expressed as the mean ± standard error of the mean (n=8). *P<0.01 vs. NOR group; #P<0.01 vs. DM group. NOR, normal rat; DM, streptozotocin-induced diabetic rat; PCE-100, DM treated with 100 mg/kg PCE; PCE-350, DM treated with 350 mg/kg PCE; PCE, Polygonum cuspidatum extract; WT-1, Wilms Tumor 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581740&req=5

f1-mmr-12-04-5837: Effect of PCE on podocyte loss. Representative histology sections from the NOR, DM, PCE-100 and PCE-350 groups (magnification, ×400): (A) Synaptopodin and (B) WT-1 staining of the glomeruli. Morphometric analysis of (C) synaptopodin and (D) WT-1 in the renal cortex of rats from each group. All data are expressed as the mean ± standard error of the mean (n=8). *P<0.01 vs. NOR group; #P<0.01 vs. DM group. NOR, normal rat; DM, streptozotocin-induced diabetic rat; PCE-100, DM treated with 100 mg/kg PCE; PCE-350, DM treated with 350 mg/kg PCE; PCE, Polygonum cuspidatum extract; WT-1, Wilms Tumor 1.
Mentions: The podocyte content was determined by counting the cells that were stained with synaptopodin and WT-1, the podocyte marker (Fig. 1A and B). The number of synaptopodin- and WT-1-positive cells in the STZ-induced diabetic rat group was reduced compared with that of the normal control rats (P<0.01). Treatment with PCE markedly increased the podocyte content in the renal glomeruli in a dose-dependent manner (P<0.01; Fig. 1B and C).

Bottom Line: However, treatment with PCE for 16 weeks restored protein levels to normal, and reduced podocyte loss and apoptosis.Levels of caspase‑3 and MGO expression, as well as oxidative stress were ameliorated by PCE treatment.In addition, emodin, a biologically active ingredient of PCE, exerted an MGO scavenging effect and inhibited MGO‑derived advanced glycation end‑product formation.

View Article: PubMed Central - PubMed

Affiliation: Korean Medicine Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 305‑811, Republic of Korea.

ABSTRACT
Podocyte injury contributes to renal damage and, eventually, to the occurrence of proteinuria in diabetic nephropathy. The aim of the present study was to investigate the effect of an ethanol extract from Rhizoma Polygonum cuspidatum (P. cuspidatum) on proteinuria and podocyte injury, and elucidate the underlying mechanism for streptozotocin (STZ)‑induced diabetic nephropathy. The protective effects of P. cuspidatum extract (PCE) on renal podocytes in STZ‑induced diabetic rats were also investigated. PCE (100 or 350 mg/kg/day) was administered to STZ‑induced diabetic rats for 16 weeks, and blood glucose levels, body weight and proteinuria were measured. A double labeling technique with the terminal deoxynucleotidyl transferase dUTP nick end labeling assay was performed and synaptopodin expression was observed. In addition, cleaved caspase‑3, methylglyoxal (MGO) and 8‑hydroxydeoxyguanosine (8‑OHdG) expression levels were measured. STZ‑induced diabetic rats developed hyperglycemia and proteinuria. Increased apoptosis of the podocytes and increased cleaved caspase‑3, MGO and 8‑OHdG expression levels, as well as decreased synaptopodin expression were detected in the glomeruli of STZ‑induced diabetic rats. However, treatment with PCE for 16 weeks restored protein levels to normal, and reduced podocyte loss and apoptosis. Levels of caspase‑3 and MGO expression, as well as oxidative stress were ameliorated by PCE treatment. In addition, emodin, a biologically active ingredient of PCE, exerted an MGO scavenging effect and inhibited MGO‑derived advanced glycation end‑product formation. These findings indicate that PCE may be administered to prevent proteinuria and podocyte loss in STZ‑induced diabetic rats partly by inhibiting podocyte apoptosis and cleaved caspase‑3 expression, and by restoring the balance of oxidative stress and MGO expression.

Show MeSH
Related in: MedlinePlus