Ginsenoside Rb1, a panoxadiol saponin against oxidative damage and renal interstitial fibrosis in rats with unilateral ureteral obstruction.
OBJECTIVE
To investigate the possible protective effect and mechanism of ginsenoside Rb1 against oxidative damage and renal interstitial fibrosis on rats with unilateral ureteral obstruction (UUO).


METHODS
In total, 80 male rats were randomly divided into 4 groups, 20 in each group: the sham operated group (SOR), UUO group, UUO with ginsenoside Rb1 treatment group (treated with intraperitoneal injection of 50 mg/ kg daily) and UUO with Losartan treatment group (as the positive control, treated with 20 mg/kg by gastrogavage per day). The rats were randomly sacrificed on day 3, 7 and 14 after surgery, respectively. The histopathologic changes of renal interstitial tissues were observed with Masson staining. The mRNA of transforming growth factor beta 1 (TGF-beta 1), collagen I and fibronectin were reversed transcribed and quantified by Real-time PCR. Enzyme-linked immunosorbent assay was used to quantitatively detect TGF-beta 1 and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. P47phox protein expression was assessed by immunohistochemistry and Western blot analysis.


RESULTS
In the UUO model, the obstructed kidney showed typical features of progressive renal tubulointerstitial fibrosis, and the levels of TGF-beta1, collagen I and fibronectin increased (P<0.05). As compared with the UUO group, ginsennoside Rb1 significantly inhibited the interstitial fibrosis including tubular injury and collagen deposition, and decreased the levels of TGF-beta1 (P<0.05). Ginsenoside Rb1 also inhibited the heme oxygenase (HO-1) and 8-OHdG, two markers of oxidative stress (P<0.05). Moreover, ginsenoside Rb1 suppressed the expression of p47phox, a subunit of nicotinamide adeninedinucleotide phosphate (NADPH) oxidase (P<0.05).


CONCLUSIONS
Ginsenoside Rb1 can obviously inhibit renal interstitial fibrosis in rats with UUO, its mechanism possibly via against the oxidative damage and suppressing TGF-beta1 expression.
Xie
Xi-sheng
XS
Department of Nephrology, West China Hospital, Sichuan University, Chengdu, 610041, China.
Liu
Heng-chuan
HC
Yang
Man
M
Zuo
Chuan
C
Deng
Yao
Y
Fan
Jun-ming
JM
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D004353:Drug Evaluation, Preclinical; D005355:Fibrosis / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D005786:Gene Expression Regulation / Q000187:drug effects; D036145:Ginsenosides / Q000627:therapeutic use*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D007674:Kidney Diseases / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008954:Models, Biological; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000627:therapeutic use; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014517:Ureteral Obstruction / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism
D036145:Ginsenosides; D012503:Saponins; D053773:Transforming Growth Factor beta1; C442759:ginsenoside Rb1; D000080242:8-Hydroxy-2'-Deoxyguanosine; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D003849:Deoxyguanosine