Peroxisome proliferator-activated receptor-γ activators monascin and rosiglitazone attenuate carboxymethyllysine-induced fibrosis in hepatic stellate cells through regulating the oxidative stress pathway but independent of the receptor for advanced glycation end products signaling
Journal
Journal of Agricultural and Food Chemistry
Journal Volume
61
Journal Issue
28
Pages
6873-6879
Date Issued
2013
Author(s)
Abstract
Advanced glycation end products (AGEs) signaling through its receptors (RAGE) results in an increase in reactive oxygen species (ROS) and is thought to contribute to hepatic fibrosis via hyperglycemia. Carboxymethyllysine (CML) is a key AGE, with highly reactive dicarbonyl metabolites. We investigated the inhibitory effect of Monascus-fermented metabolite monascin and rosiglitazone on CML-induced RAGE signaling in hepatic stellate cells (HSCs) and its resulting antihepatic fibrosis activity. We found that monascin and rosiglitazone upregulated peroxisome proliferator-activated receptor-γ (PPAR-γ) to attenuate α-smooth muscle actin (SMA) and ROS generation in CML-treated HSCs in a RAGE activation-independent pathway. Therefore, monascin may delay or inhibit the progression of liver fibrosis through the activation of PPAR-γ and might prove to be a major antifibrotic mechanism to prevent liver disease. © 2013 American Chemical Society.
Type
journal article