Puerarin attenuated early diabetic kidney injury through down-regulation of matrix metalloproteinase 9 in streptozotocin-induced diabetic rats.
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.
Division of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Yifei
Y
Zhong
Division of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Xianwen
X
Zhang
Division of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Xianfan
X
Cai
National Engineering Research Center for Biochip at Shanghai, Shanghai, China.
Ke
K
Wang
Division of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Yiping
Y
Chen
Division of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Yueyi
Y
Deng
D000818:Animals; D024141:Collagen Type IV / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000201:enzymology*; D003928:Diabetic Nephropathies / Q000201:enzymology* / Q000517:prevention & control; D004353:Drug Evaluation, Preclinical; D004794:Enzyme Repression; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology* / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D050199:Podocytes / Q000187:drug effects; D011507:Proteinuria / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013311:Streptozocin
D024141:Collagen Type IV; D047908:Intracellular Signaling Peptides and Proteins; D007529:Isoflavones; D008565:Membrane Proteins; C407223:NPHS2 protein; D017382:Reactive Oxygen Species; C113267:nephrin; D013311:Streptozocin; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; D019808:Losartan; C033607:puerarin