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.

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.
Authors	Wei-Hsuan Hsu, Bao-Hong Lee, Ya-Wen Hsu, Tzu-Ming Pan
Journal	Journal of agricultural and food chemistry (J Agric Food Chem) Vol. 61 Issue 28 Pg. 6873-9 (Jul 17 2013) ISSN: 1520-5118 [Electronic] United States
PMID	23796251 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Anti-Inflammatory Agents Heterocyclic Compounds, 3-Ring PPAR gamma RNA, Small Interfering Receptor for Advanced Glycation End Products Receptors, Immunologic Thiazolidinediones beta-Glucans micellapist Rosiglitazone N(6)-carboxymethyllysine Lysine monascin
Topics	Animals Anti-Inflammatory Agents (pharmacology) Cells, Cultured Hepatic Stellate Cells (drug effects, pathology) Heterocyclic Compounds, 3-Ring (pharmacology) Liver Cirrhosis (chemically induced, prevention & control) Lysine (analogs & derivatives, pharmacology) Male Mice Oxidative Stress (drug effects) PPAR gamma (drug effects, physiology) RNA, Small Interfering (genetics) Receptor for Advanced Glycation End Products Receptors, Immunologic (antagonists & inhibitors, physiology) Rosiglitazone Signal Transduction (drug effects) Thiazolidinediones (pharmacology) Transfection beta-Glucans

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