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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 the apoptosis of podocytes. (A) Dual-labeling for TUNEL (brown) and synaptopodin (red) in kidney sections from the NOR, DM, PCE-100 and PCE-350 groups (magnification, ×400). Morphometric analysis of (B) the positive area of synaptopodin expression and (C) TUNEL and synaptopodin double-positive cells. Hematoxylin (blue) was used to counterstain the nucleus in (A). 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, Polygonum cuspidatum extract; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling.
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f2-mmr-12-04-5837: Effect of PCE on the apoptosis of podocytes. (A) Dual-labeling for TUNEL (brown) and synaptopodin (red) in kidney sections from the NOR, DM, PCE-100 and PCE-350 groups (magnification, ×400). Morphometric analysis of (B) the positive area of synaptopodin expression and (C) TUNEL and synaptopodin double-positive cells. Hematoxylin (blue) was used to counterstain the nucleus in (A). 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, Polygonum cuspidatum extract; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling.

Mentions: To determine the anti-apoptotic effect of PCE, the double labeling technique for TUNEL and synaptopodin was performed. A reduced number of synaptopodin-labeled cells was observed in the glomeruli of STZ-induced diabetic rats compared with the normal control rats (P<0.01). However, in the PCE-treated diabetic rats, the level of synaptopodin-positive cells had increased compared with the STZ-induced diabetic rats (P<0.01). TUNEL-positive cells co-localized to the region of synaptopodin expression in the double labeling-stained kidney section, which is consistent with the apoptosis of podocytes in the STZ-induced diabetic rat glomeruli (Fig. 2A). In the STZ-induced diabetic rats, the number of TUNEL-positive cells was markedly increased compared with that observed in the normal control rats (P<0.01). PCE treatment was effective in reducing the apoptotic signal in STZ-induced diabetic rats (Fig. 2B 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 the apoptosis of podocytes. (A) Dual-labeling for TUNEL (brown) and synaptopodin (red) in kidney sections from the NOR, DM, PCE-100 and PCE-350 groups (magnification, ×400). Morphometric analysis of (B) the positive area of synaptopodin expression and (C) TUNEL and synaptopodin double-positive cells. Hematoxylin (blue) was used to counterstain the nucleus in (A). 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, Polygonum cuspidatum extract; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2-mmr-12-04-5837: Effect of PCE on the apoptosis of podocytes. (A) Dual-labeling for TUNEL (brown) and synaptopodin (red) in kidney sections from the NOR, DM, PCE-100 and PCE-350 groups (magnification, ×400). Morphometric analysis of (B) the positive area of synaptopodin expression and (C) TUNEL and synaptopodin double-positive cells. Hematoxylin (blue) was used to counterstain the nucleus in (A). 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, Polygonum cuspidatum extract; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling.
Mentions: To determine the anti-apoptotic effect of PCE, the double labeling technique for TUNEL and synaptopodin was performed. A reduced number of synaptopodin-labeled cells was observed in the glomeruli of STZ-induced diabetic rats compared with the normal control rats (P<0.01). However, in the PCE-treated diabetic rats, the level of synaptopodin-positive cells had increased compared with the STZ-induced diabetic rats (P<0.01). TUNEL-positive cells co-localized to the region of synaptopodin expression in the double labeling-stained kidney section, which is consistent with the apoptosis of podocytes in the STZ-induced diabetic rat glomeruli (Fig. 2A). In the STZ-induced diabetic rats, the number of TUNEL-positive cells was markedly increased compared with that observed in the normal control rats (P<0.01). PCE treatment was effective in reducing the apoptotic signal in STZ-induced diabetic rats (Fig. 2B 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