PMID- 21367880
OWN - NLM
STAT- MEDLINE
DCOM- 20110616
LR  - 20110411
IS  - 1535-3699 (Electronic)
IS  - 1535-3699 (Linking)
VI  - 236
IP  - 4
DP  - 2011 Apr 1
TI  - Isoangustone A suppresses mesangial fibrosis and inflammation in human renal 
      mesangial cells.
PG  - 435-44
LID - 10.1258/ebm.2010.010325 [doi]
AB  - Development of diabetic nephropathy with fibrosis is associated with 
      hypereglycemia-linked inflammation. Increased levels of proinflammatory factors 
      have been found in diabetic patients with nephropathy. The present study was to 
      test the hypothesis that isoangustone A, a novel compound present in licorice, 
      can inhibit renal fibrosis and inflammation inflamed by high glucose (HG) in 
      human mesangial cells through disturbing transforming growth factor beta (TGF-beta) and 
      nuclear facor kappaB (NF-kappaB) pathways. Serum-starved mesangial cells were cultured in 
      33 mmol/L glucose media. Cells were treated with 1-20 mumol/L isoangustone A 
      isolated from Glycyrrhiza uralensis licorice for three days. Exposure of cells to 
      HG elevated connective tissue growth factor and collagen production, which was 
      dose-dependently reversed by isoangustone A. Isoangustone A boosted HG-plummeted 
      membrane type matrix metalloproteinase (MMP)-1 expression and diminished 
      HG-elevated tissue inhibitor of MMP-2 expression. HG activated mesangial 
      TGF-beta1-SMAD-responsive signaling, which was repealed by >/=10 mumol/L isoangustone 
      A. Furthermore, HG upregulated intracellular cell adhesion molecule-1 (ICAM-1) 
      level and monocyte chemoattractant protein-1 (MCP-1) mRNA expression, and such 
      increases were dose-dependently suppressed by isoangustone A most likely through 
      hampering TGF-beta signaling pathways. Blockade of NF-kappaB signaling appeared to be 
      responsible for attenuating HG-triggered induction of ICAM-1 and MCP-1. Our 
      findings provide the first evidence that isoangustone A dampens mesangial 
      sclerosis associated with inflammation in response to HG through hindering TGF-beta 
      and NF-kappaB signaling.
FAU - Li, Jing
AU  - Li J
AD  - Department of Food and Nutrition, Hallym University, Chuncheon, Kangwon-do 
      200-702, South Korea.
FAU - Lim, Soon Sung
AU  - Lim SS
FAU - Lee, Eun-Sook
AU  - Lee ES
FAU - Gong, Ju-Hyun
AU  - Gong JH
FAU - Shin, Daekeun
AU  - Shin D
FAU - Kang, Il-Jun
AU  - Kang IJ
FAU - Kang, Young-Hee
AU  - Kang YH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110302
PL  - Switzerland
TA  - Exp Biol Med (Maywood)
JT  - Experimental biology and medicine (Maywood, N.J.)
JID - 100973463
RN  - 0 (Isoflavones)
RN  - 0 (isoangustone A)
SB  - IM
MH  - Fibrosis
MH  - Glomerular Mesangium/*drug effects/pathology/physiopathology
MH  - Humans
MH  - Inflammation/*chemically induced
MH  - Isoflavones/*pharmacology
EDAT- 2011/03/04 06:00
MHDA- 2011/06/17 06:00
CRDT- 2011/03/04 06:00
PHST- 2011/03/04 06:00 [entrez]
PHST- 2011/03/04 06:00 [pubmed]
PHST- 2011/06/17 06:00 [medline]
AID - ebm.2010.010325 [pii]
AID - 10.1258/ebm.2010.010325 [doi]
PST - ppublish
SO  - Exp Biol Med (Maywood). 2011 Apr 1;236(4):435-44. doi: 10.1258/ebm.2010.010325. 
      Epub 2011 Mar 2.