title: Emodin Inhibits Homocysteine-Induced C-Reactive Protein Generation in Vascular Smooth Muscle Cells by Regulating PPARγ Expression and ROS-ERK1/2/p38 Signal Pathway.
abstract: Atherosclerosis is an inflammatory disease. As an inflammatory molecule, C-reactive protein (CRP) plays a direct role in atherogenesis. It is known that the elevated plasma homocysteine (Hcy) level is an independent risk factor for atherosclerosis. We previously reported that Hcy produces a pro-inflammatory effect by inducing CRP expression in vascular smooth muscle cells (VSMCs). In the present study, we observed effect of emodin on Hcy-induced CRP expression in rat VSMCs and molecular mechanisms. The in vitro results showed that pretreatment of VSMCs with emodin inhibited Hcy-induced mRNA and protein expression of CRP in a concentration-dependent manner. The in vivo experiments displayed that emodin not only inhibited CRP expression in the vessel walls in mRNA and protein levels, but also reduced the circulating CRP level in hyperhomocysteinemic rats. Further study revealed that emodin diminished Hcy-stimulated generation of reactive oxygen species (ROS), attenuated Hcy-activated phosphorylation of ERK1/2 and p38, and upregulated Hcy-inhibited expression of peroxisome proliferator-activated receptor gamma (PPARγ) in VSMCs. These demonstrate that emodin is able to inhibit Hcy-induced CRP generation in VSMCs, which is related to interfering with ROS-ERK1/2/p38 signal pathway and upregulating PPARγ expression. The present study provides new evidence for the anti-inflammatory and anti-atherosclerotic effects of emodin.
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an, China; Department of Clinical Pharmacy, Central Hospital of Zibo, Zibo, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Pang
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an, China.
authors.forename: Juntian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Clinical Pharmacy, Central Hospital of Zibo, Zibo, China.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an, China.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002097:C-Reactive Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004642:Emodin / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006710:Homocysteine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D020138:Hyperhomocysteinemia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D047495:PPAR gamma; D017382:Reactive Oxygen Species; D006710:Homocysteine; D002097:C-Reactive Protein; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D004642:Emodin