The Ayurvedic Medicine Salacia oblonga Attenuates Diabetic Renal Fibrosis in Rats: Suppression of Angiotensin II/AT1 Signaling.
In human diabetic nephropathy, the extent of tubulointerstitial fibrosis is the leading cause of end-stage renal disease; fibrosis is closely correlated with renal dysfunction. Although a wide array of medicinal plants play a role in the prevention and treatment of diabetes, there are few reports of the application of herbal medicines in amelioration of renal fibrosis, or the underlying mechanisms by which such benefits are mediated. The efficacy of the Ayurvedic antidiabetic medicine Salacia oblonga (SO) root on rat renal fibrosis was investigated. An aqueous extract from SO (100 mg/kg, p.o., 6 weeks) diminished renal glomerulosclerosis and interstitial fibrosis in Zucker diabetic fatty (ZDF) rats, as revealed by van Giesen-staining. SO also reduced renal salt-soluble, acid-soluble and salt-insoluble collagen contents. These changes were accompanied by normalization of hypoalbuminemia and BUN. Gene profiling revealed that the increase in transcripts encoding the glomerulosclerotic mediators collagen I, collagen IV, fibronectin, angiotensin II type 1 receptor (AT1), transforming growth factor (TGF)-β1, plasminogen activator inhibitor (PAI)-1 observed in ZDF rat kidney was suppressed by SO. In rat-derived mesangial cells, similar to the effect of the AT1 antagonist telmisartan, SO and its major component mangiferin suppressed the stimulatory effect of angiotensin II on proliferation and increased mRNA expression and/or activities of collagen I, collagen IV, fibronectin, AT1, TGF-β1 and PAI-1. Considered together the present findings demonstrate that SO attenuates diabetic renal fibrosis, at least in part by suppressing anigiotensin II/AT1 signaling. Further, it now emerges that mangiferin is an effective antifibrogenic agent.
He
Lan
L
School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China.
Qi
Yanfei
Y
Rong
Xianglu
X
Jiang
Jianmin
J
Yang
Qinglin
Q
Yamahara
Johji
J
Murray
Michael
M
Li
Yuhao
Y
Kidney Int. 1994 Jan;45(1):177-84
8127007
Kidney Int. 2006 Dec;70(11):1914-9
16985515
Diabetes. 1994 Aug;43(8):1046-51
8039599
Circulation. 2002 Sep 24;106(13):1722-8
12270869
Evid Based Complement Alternat Med. 2005 Dec;2(4):465-73
16322803
Evid Based Complement Alternat Med. 2008 Mar;5(1):1-2
18317542
Kidney Int. 2002 Jan;61(1 Suppl):S106-9
11841622
Life Sci. 2004 Aug 20;75(14):1735-46
15268973
Evid Based Complement Alternat Med. 2008 Jun;5(2):121-2
18604248
Diabetes Obes Metab. 2008 Jul;10(7):574-85
17645561
J Clin Invest. 1994 Jun;93(6):2431-7
8200978
Yakugaku Zasshi. 2001 May;121(5):371-8
11360491
Diabetes Metab Res Rev. 2008 Sep;24(6):498-506
18613221
Am J Nephrol. 2008;28(4):548-54
18239381
Am J Physiol Renal Physiol. 2002 Aug;283(2):F209-20
12110504
J Clin Invest. 2003 Aug;112(3):326-8
12897200
EMBO J. 1987 May;6(5):1281-6
3111844
Pathol Res Pract. 1980;167(2-4):204-16
7433232
J Clin Invest. 2006 Feb;116(2):288-96
16453013
Hypertension. 2001 Sep;38(3 Pt 2):635-8
11566946
Curr Opin Nephrol Hypertens. 2004 May;13(3):279-84
15073485
Diabetes. 1999 Oct;48(10):2066-73
10512375
Phytother Res. 2007 Jan;21(1):1-16
16927447
Nephrol Dial Transplant. 2006 Jan;21(1):16-20
16280370
Life Sci. 2008 May 23;82(21-22):1045-9
18433791
Am J Nephrol. 2003 Jul-Aug;23(4):222-8
12840598
J Am Soc Nephrol. 1995 Jan;5(7):1492-7
7703388
Am J Pathol. 1992 Jan;140(1):95-107
1731533
J Clin Invest. 2007 Mar;117(3):524-9
17332879
J Vasc Surg. 2005 Jul;42(1):140-8
16012463
Circulation. 2005 Apr 19;111(15):1962-9
15837950
Kidney Int. 1993 Mar;43(3):661-7
8455365
Diabetes. 1989 Sep;38(9):1077-81
2670639
Toxicol Appl Pharmacol. 2006 Feb 1;210(3):225-35
15975614
Toxicol Appl Pharmacol. 2006 Jan 1;210(1-2):78-85
16129467
Kidney Int. 1999 Nov;56(5):1627-37
10571771