title: Panax notogingseng saponins suppress RAGE/MAPK signaling and NF-kappaB activation in apolipoprotein-E-deficient atherosclerosis-prone mice.
abstract: BACKGROUND
  Panax notoginseng saponins (PNS) extracted from the roots of panax notoginseng are free radical-scavenger, with an antioxidant property, capable of inhibiting expression of adhesion molecules and chemokines. This study was designed to test the effects of PNS administration in apolipoprotein (apo)-E-deficient mice on the activation of JNK, p38(MAPK), ERK1/2 and NF-κB, and the expression of RAGE, adhesion molecules and chemokines in the atherosclerotic lesions.
  
  
  METHODS
  Wild type and apoE-null mice (male, 10-week-old) were treated with PNS for 4 weeks. Peripheral blood was collected for assessing the serum levels of glucose, lipids and MDA, and activities of SOD and GSH. The sizes of atherosclerotic lesions and numbers of macrophages in the branchiocephalic arteries, and the reactive oxygen species (ROS) production in the aortic root were analyzed. The levels of CD68, Galectin-3, RAGE, JNK, phosphor-JNK, p38(MAPK), phosphor-p38(MAPK), ERK1/2, phosphor-ERK1/2, I-κB, phosphor-I-κB (Ser32), NF-κB, phosphor-NF-κB, MCP-1, VCAM-1 and ICAM-1 in the descending arteries were identified by Western blot.
  
  
  RESULTS
  The atherosclerotic lesion sizes, and macrophage numbers, but not the smooth muscle cell amounts and the collagen content, were decreased in apoE(-/-) mice treated with PNS. After PNS administration for 4 weeks, the apoE(-/-) mice displayed reduced level of serum MDA and enhanced activity of SOD and GSH, accompanied by impaired ROS generation in the aortic root. Moreover, PNS down-regulated the expression of VCAM-1, ICAM-1 and MCP-1, accompanied by reduced expression of RAGE and suppressed the activation of NF-κB, JNK, p38(MAPK) and ERK1/2.
  
  
  CONCLUSIONS
  PNS may inhibit progression of atherosclerotic lesions via their antioxidant/anti-inflammatory biological properties. PNS suppress the RAGE/MAPK signaling pathways, inactivate NF-κB, and reduce expression of pro-inflammatory factors, such as VCAM-1, ICAM-1 and MCP-1 in atherosclerotic lesions of apoE(-/-) mice.
authors.affiliation: Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Dou
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Lu
authors.forename: Tao
authors.initials: T
authors.lastname: Shen
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Huang
authors.forename: Yong
authors.initials: Y
authors.lastname: Man
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000201:enzymology / Q000378:metabolism*; D015153:Blotting, Western; D004789:Enzyme Activation; D007150:Immunohistochemistry; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005894:Panax / Q000737:chemistry*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D012503:Saponins; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4