Ethanol extracts of Rehmannia complex (Di Huang) containing no Corni fructus improve early diabetic nephropathy by combining suppression on the ET-ROS axis with modulate hypoglycemic effect in rats.
OBJECTIVE
Liuwei Dihuang (Rehmannia complex, RC) decoction, a classic prescription of Traditional Chinese Medicine (TCM), has been used in treating diabetic nephropathy (DN). Among the 6 crude medicines which contains Corni fructus is recognized as the active fraction for its effectiveness. We aimed to investigate, first, if without Corni fructus a modified RC could be still effective, second, if the ethanol extracts could be better than that of water extract and third, the beneficial effect is mainly stemmed from suppressing the endothelin (ET-1) pathway associated with a moderate hypoglycemic effect.


METHODS
Diabetes for 8 weeks was induced by a single dose of streptozotocin (STZ, 65 mg/kg, i.p.) in rats and treated with RC extracts in either 95%, 70% ethanol or water separately during 5-8th week. The efficacy of extracts was compared with aminoguanidine (AMG).


RESULTS
An increase in albumin and creatinine in 24h urine, blood urea nitrogen (BUN) was found in STZ rats. Oxidative stress was found in renal cortex in association with upregulated plasma ET-1 and mRNA of ETA, decreased MMP 2,9 (matrix matelloproteinases) and increased hydroxyproline.


CONCLUSIONS
The RC without Corni fructus was very effective in alleviating DN and ethanol extracts provided greater effects against water extracts. The efficacy in alleviating DN is attributed to normalizing the activated ET system, oxidative stress and MMP 2,9 in combination with a moderate hypoglycemic activity.
Liu
Hao-Ran
HR
Research Division of Pharmacology, China Pharmaceutical University, Nanjing, China.
Tang
Xiao-Yun
XY
Dai
De-Zai
DZ
Dai
Yin
Y
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D019332:Endothelin-1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D005260:Female; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008516:Medicine, Chinese Traditional; D009569:Nitric Oxide / Q000032:analysis; D008517:Phytotherapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013311:Streptozocin
D004365:Drugs, Chinese Herbal; D019332:Endothelin-1; D007004:Hypoglycemic Agents; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D013311:Streptozocin; D020778:Matrix Metalloproteinase 2