TY - JOUR
T1 - Suppression of dimerumic acid on hepatic fibrosis caused from carboxymethyl-lysine (CML) by attenuating oxidative stress depends on Nrf2 activation in hepatic stellate cells (HSCs)
AU - Lee, Bao Hong
AU - Hsu, Wei Hsuan
AU - Hsu, Ya Wen
AU - Pan, Tzu Ming
N1 - Funding Information:
The authors would like to express our gratitude to National Science Council, ROC, for supporting this research work (NSC100-2628-B-002-004-MY2) and subsidiary. In addition, authors wish to thank Dr. She-Ching Wu (Department of Food Science, National Chiayi University, Chiayi, Taiwan) for kindly providing HSCs isolated from C57BL/6 mice.
PY - 2013/12
Y1 - 2013/12
N2 - Hyperglycemia facilitates the formation of advanced glycation end-products (AGEs) in type-2 diabetes. Evidence indicates that carboxymethyl-lysine (CML) is highly prevalent in diabetes, resulting in hepatic fibrosis. The current study was designed to evaluate the effects of dimerumic acid (DMA) identified from Monascus-fermented products on receptor for AGEs (RAGE) signal and hepatic stellate cells (HSCs) activation by CML treatment. We found that DMA (50. μM) eliminated collagen generation, mRNA expressions of α-smooth muscle actin (α-SMA), platelet-derived growth factor-β receptor (PDGF-βR), and procollagen 1a1 (proCol-1a1) in CML (100. μg/ml)-treated HSCs, and these effects were similar to allyl isothiocyanate (AITC; 50. μM). In addition, the suppression of α-SMA, PDGF-βR, proCol-1a1 by DMA were abolished while nuclear factor-erythroid 2-related factor 2 (Nrf2) silence in CML-treated HSCs. These findings suggested that DMA and AITC increased Nrf2 and glutamate-cysteine ligase (GCL) activities thereby inhibiting oxidative stress caused by CML and showing anti-fibrogentic effect in HSCs.
AB - Hyperglycemia facilitates the formation of advanced glycation end-products (AGEs) in type-2 diabetes. Evidence indicates that carboxymethyl-lysine (CML) is highly prevalent in diabetes, resulting in hepatic fibrosis. The current study was designed to evaluate the effects of dimerumic acid (DMA) identified from Monascus-fermented products on receptor for AGEs (RAGE) signal and hepatic stellate cells (HSCs) activation by CML treatment. We found that DMA (50. μM) eliminated collagen generation, mRNA expressions of α-smooth muscle actin (α-SMA), platelet-derived growth factor-β receptor (PDGF-βR), and procollagen 1a1 (proCol-1a1) in CML (100. μg/ml)-treated HSCs, and these effects were similar to allyl isothiocyanate (AITC; 50. μM). In addition, the suppression of α-SMA, PDGF-βR, proCol-1a1 by DMA were abolished while nuclear factor-erythroid 2-related factor 2 (Nrf2) silence in CML-treated HSCs. These findings suggested that DMA and AITC increased Nrf2 and glutamate-cysteine ligase (GCL) activities thereby inhibiting oxidative stress caused by CML and showing anti-fibrogentic effect in HSCs.
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U2 - 10.1016/j.fct.2013.09.007
DO - 10.1016/j.fct.2013.09.007
M3 - Article
C2 - 24036144
AN - SCOPUS:84884709820
SN - 0278-6915
VL - 62
SP - 413
EP - 419
JO - Food and Chemical Toxicology
JF - Food and Chemical Toxicology
ER -
