Abstract
Radix puerariae, a traditional Chinese herbal medication, has been used successfully to treat patients with early stage of diabetic nephropathy. However, the underlined mechanism of this renal protective effect has not been determined. In the current study, we investigated the effects and the mechanism of puerarin in Streptozotocin (STZ)-induced diabetic rats. We treated STZ-rats with either puerarin or losartan, an angiotensin II receptor blocker, as compared to those treated with vehicle. We found that both puerarin and losartan attenuated kidney hypertrophy, mesangial expansion, proteinuria, and podocyte foot process effacement in STZ rats. In addition, both puerarin and losartan increased expression of podocyte slit diaphragm proteins such as nephrin and podocin. Interestingly, we found that puerarin treatment induced a more pronounced suppression of oxidative stress production and S-nitrosylation of proteins in the diabetic kidneys as compared to losartan treatment. Furthermore, we found that matrix metalloproteinase-9 (MMP-9), which is known to be activated by oxidative stress and S-nitrosylation of proteins, was also suppressed more extensively by puerarin than losartan. In conclusion, these data provide for the first time the potential mechanism to support the use of puerarin in the treatment of early diabetic nephropathy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Collagen Type IV / metabolism
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Diabetes Mellitus, Experimental / complications
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Diabetes Mellitus, Experimental / enzymology*
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Diabetic Nephropathies / enzymology*
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Diabetic Nephropathies / prevention & control
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Drug Evaluation, Preclinical
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Enzyme Repression
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Intracellular Signaling Peptides and Proteins / metabolism
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Isoflavones / pharmacology*
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Isoflavones / therapeutic use
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Kidney / drug effects
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Kidney / enzymology
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Losartan / pharmacology
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Male
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Matrix Metalloproteinase 9 / genetics*
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Matrix Metalloproteinase 9 / metabolism
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Membrane Proteins / metabolism
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Podocytes / drug effects
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Proteinuria / prevention & control
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Rats
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Rats, Wistar
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Reactive Oxygen Species / metabolism
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Streptozocin
Substances
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Collagen Type IV
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Intracellular Signaling Peptides and Proteins
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Isoflavones
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Membrane Proteins
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NPHS2 protein
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Reactive Oxygen Species
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nephrin
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Streptozocin
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Matrix Metalloproteinase 9
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Mmp9 protein, rat
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Losartan
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puerarin
Grants and funding
YF Zhong is supported by National Natural Science Foundation of China for Young Investigators (1999-30901944) and Shanghai Bureau of Health for Young Investigators (2011- XYQ2011059); YY Deng is supported by National Natural Science Foundation of China (30973725); XW Zhang is supported by Shanghai Natural Science Foundation for Young Investigators (2012-ZR1450500); XF Cai is supported by Graduate student creative project of the Shanghai University of Traditional Chinese Medicine (22). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.