Skimmin, a coumarin, suppresses the streptozotocin-induced diabetic nephropathy in wistar rats.
Skimmin, a major active ingredient from Hydrangea paniculata, was considered to have the possible preventive effect on the progression of diabetic nephropathy based on the traditional Chinese medicine. The present study aimed to assess this preventive activity in a rat model of diabetic nephropathy. Adult wistar rats were induced to develop diabetic nephropathy through injection of streptozotocin (60mg/kg). Animals were treated orally with saline, skimmin at 7.5, 15 and 30mg/kg, and losartan (10mg/kg) daily for 17 weeks. At 7 and 17 weeks, blood and urine samples were collected for biochemical examination; at the end of 17 weeks, all the kidney tissues were collected for the histological examination. Enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR) were used to analyze the expression of transforming growth factor-beta 1(TGF-β1) and its receptors in blood and kidney tissues respectively. Our results suggested that skimmin could decrease the Scr and glucose level in blood of diabetic rats significantly (P<0.01), and increase the creatinine clearance (P<0.01), similar changes were also observed in the losartan-treated rats. In histological examination, skimmin-treated rats showed a significant decrease in glomcrulus segmented sclerosis and incidence of tubule vacuolar degeneration (P<0.01), similar but less significant beneficial effects were observed for losartan treatment. By ELISA, western blotting and RT-PCR, we found skimmin could down-regulate the TGF-β1 and TGF-β Receptor I expression both at protein and mRNA levels. This study suggests that the skimmin can suppress diabetic nephropathy in rats effectively, and may slow down the renal fibrosis by regulating TGF-β1 signal pathway.
State key laboratory of bioactive substances and functions of natural medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union medical college, Beijing, 100050, PR China.
Sen
S
Zhang
Jingzhi
J
Yang
Hongyan
H
Li
Yan
Y
Li
Yue
Y
Liu
Dongming
D
Zhang
Furong
F
Zhang
Wanqi
W
Zhou
Xiaoguang
X
Chen
D000818:Animals; D003374:Coumarins / Q000494:pharmacology* / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000235:genetics
D003374:Coumarins; D007004:Hypoglycemic Agents; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C030123:coumarin; C581268:skimmin