Curcumin attenuates diabetic nephropathy by inhibiting PKC-α and PKC-β1 activity in streptozotocin-induced type I diabetic rats

Vivian Soetikno, Kenichi Watanabe, Flori R. Sari, Meilei Harima, Rajarajan A. Thandavarayan, Punniyakoti T. Veeraveedu, Wawaimuli Arozal, Vijayakumar Sukumaran, Arun Lakshmanan, Somasundaram Arumugam, Kenji Suzuki

Research output: Contribution to journalArticle

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Abstract

Scope: We hypothesized that curcumin, a potent anti-oxidant, might be beneficial in ameliorating the development of diabetic nephropathy through inhibition of PKC-α and PKC-β1 activity-ERK1/2 pathway. Methods and results: Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ) (55mg/kg) in rats. Three weeks after STZ injection, rats were divided into three groups, namely, normal, diabetic and diabetic treated with curcumin at 100mg/kg/day, p.o., for 8wk. At 11wk after STZ injection, diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine clearance, increased blood urea nitrogen (BUN) and proteinuria, marked increases in lipid peroxidation, NOX4 and p67phox and decrease in anti-oxidant enzyme. All of these abnormalities were significantly reversed by curcumin. Furthermore, the high-glucose-induced PKC-α and PKC-β1 activities and phosphorylated ERK1/2 was significantly diminished by curcumin. Curcumin also attenuated the expression of TGF-β1, CTGF, osteopontin, p300 and ECM proteins such as fibronectin and type IV collagen. The high-glucose-induced expression of VEGF and its receptor VEGF receptor II (flk-1) was also ameliorated by curcumin. Conclusion: These results prove that curcumin produces dual blockade of both PKC-α and PKC-β1 activities, which suggests that curcumin is a potential adjuvant therapy for the prevention and treatment of diabetic nephropathy.

Original languageEnglish
Pages (from-to)1655-1665
Number of pages11
JournalMolecular Nutrition and Food Research
Volume55
Issue number11
DOIs
Publication statusPublished - 1 Nov 2011
Externally publishedYes

Fingerprint

diabetic nephropathy
Curcumin
curcumin
streptozotocin
Diabetic Nephropathies
Streptozocin
rats
Oxidants
oxidants
vascular endothelial growth factor receptors
injection
osteopontin
Glucose
Vascular Endothelial Growth Factor Receptor-2
glucose
Vascular Endothelial Growth Factor Receptor
Injections
Osteopontin
Collagen Type IV
MAP Kinase Signaling System

Keywords

  • Curcumin
  • Diabetic nephropathy
  • Mitogen-activated protein kinase
  • Oxidative stress
  • Protein kinase C

ASJC Scopus subject areas

  • Biotechnology
  • Food Science

Cite this

Soetikno, V., Watanabe, K., Sari, F. R., Harima, M., Thandavarayan, R. A., Veeraveedu, P. T., ... Suzuki, K. (2011). Curcumin attenuates diabetic nephropathy by inhibiting PKC-α and PKC-β1 activity in streptozotocin-induced type I diabetic rats. Molecular Nutrition and Food Research, 55(11), 1655-1665. https://doi.org/10.1002/mnfr.201100080

Curcumin attenuates diabetic nephropathy by inhibiting PKC-α and PKC-β1 activity in streptozotocin-induced type I diabetic rats. / Soetikno, Vivian; Watanabe, Kenichi; Sari, Flori R.; Harima, Meilei; Thandavarayan, Rajarajan A.; Veeraveedu, Punniyakoti T.; Arozal, Wawaimuli; Sukumaran, Vijayakumar; Lakshmanan, Arun; Arumugam, Somasundaram; Suzuki, Kenji.

In: Molecular Nutrition and Food Research, Vol. 55, No. 11, 01.11.2011, p. 1655-1665.

Research output: Contribution to journalArticle

Soetikno, V, Watanabe, K, Sari, FR, Harima, M, Thandavarayan, RA, Veeraveedu, PT, Arozal, W, Sukumaran, V, Lakshmanan, A, Arumugam, S & Suzuki, K 2011, 'Curcumin attenuates diabetic nephropathy by inhibiting PKC-α and PKC-β1 activity in streptozotocin-induced type I diabetic rats', Molecular Nutrition and Food Research, vol. 55, no. 11, pp. 1655-1665. https://doi.org/10.1002/mnfr.201100080
Soetikno, Vivian ; Watanabe, Kenichi ; Sari, Flori R. ; Harima, Meilei ; Thandavarayan, Rajarajan A. ; Veeraveedu, Punniyakoti T. ; Arozal, Wawaimuli ; Sukumaran, Vijayakumar ; Lakshmanan, Arun ; Arumugam, Somasundaram ; Suzuki, Kenji. / Curcumin attenuates diabetic nephropathy by inhibiting PKC-α and PKC-β1 activity in streptozotocin-induced type I diabetic rats. In: Molecular Nutrition and Food Research. 2011 ; Vol. 55, No. 11. pp. 1655-1665.
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AU - Watanabe, Kenichi

AU - Sari, Flori R.

AU - Harima, Meilei

AU - Thandavarayan, Rajarajan A.

AU - Veeraveedu, Punniyakoti T.

AU - Arozal, Wawaimuli

AU - Sukumaran, Vijayakumar

AU - Lakshmanan, Arun

AU - Arumugam, Somasundaram

AU - Suzuki, Kenji

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N2 - Scope: We hypothesized that curcumin, a potent anti-oxidant, might be beneficial in ameliorating the development of diabetic nephropathy through inhibition of PKC-α and PKC-β1 activity-ERK1/2 pathway. Methods and results: Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ) (55mg/kg) in rats. Three weeks after STZ injection, rats were divided into three groups, namely, normal, diabetic and diabetic treated with curcumin at 100mg/kg/day, p.o., for 8wk. At 11wk after STZ injection, diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine clearance, increased blood urea nitrogen (BUN) and proteinuria, marked increases in lipid peroxidation, NOX4 and p67phox and decrease in anti-oxidant enzyme. All of these abnormalities were significantly reversed by curcumin. Furthermore, the high-glucose-induced PKC-α and PKC-β1 activities and phosphorylated ERK1/2 was significantly diminished by curcumin. Curcumin also attenuated the expression of TGF-β1, CTGF, osteopontin, p300 and ECM proteins such as fibronectin and type IV collagen. The high-glucose-induced expression of VEGF and its receptor VEGF receptor II (flk-1) was also ameliorated by curcumin. Conclusion: These results prove that curcumin produces dual blockade of both PKC-α and PKC-β1 activities, which suggests that curcumin is a potential adjuvant therapy for the prevention and treatment of diabetic nephropathy.

AB - Scope: We hypothesized that curcumin, a potent anti-oxidant, might be beneficial in ameliorating the development of diabetic nephropathy through inhibition of PKC-α and PKC-β1 activity-ERK1/2 pathway. Methods and results: Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ) (55mg/kg) in rats. Three weeks after STZ injection, rats were divided into three groups, namely, normal, diabetic and diabetic treated with curcumin at 100mg/kg/day, p.o., for 8wk. At 11wk after STZ injection, diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine clearance, increased blood urea nitrogen (BUN) and proteinuria, marked increases in lipid peroxidation, NOX4 and p67phox and decrease in anti-oxidant enzyme. All of these abnormalities were significantly reversed by curcumin. Furthermore, the high-glucose-induced PKC-α and PKC-β1 activities and phosphorylated ERK1/2 was significantly diminished by curcumin. Curcumin also attenuated the expression of TGF-β1, CTGF, osteopontin, p300 and ECM proteins such as fibronectin and type IV collagen. The high-glucose-induced expression of VEGF and its receptor VEGF receptor II (flk-1) was also ameliorated by curcumin. Conclusion: These results prove that curcumin produces dual blockade of both PKC-α and PKC-β1 activities, which suggests that curcumin is a potential adjuvant therapy for the prevention and treatment of diabetic nephropathy.

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