title: A novel pentacyclic triterpenoid, Ilexgenin A, shows reduction of atherosclerosis in apolipoprotein E deficient mice.
abstract: Ilexgenin A (IA), a novel pentacyclic triterpenoid, is a compound extracted from leaves of Ilex hainanensis Merr. In this study, we explored the efficacy of IA on atherosclerosis and its underlying mechanism. We determined that treatment with IA attenuated atherosclerosis in high-fat diet-induced apolipoprotein E deficient mice via a series of effects involving regulation of lipid parameters, decrease of atherosclerosis-related indexes, inhibition of inflammatory cytokines secretion and pathological changes of main organs. Furthermore, the underlying mechanism of IA was investigated on oxidized low-density lipoprotein (Ox-LDL)-induced THP-1 cells. We showed that pre-treatment with IA decreased active inflammation cytokines involving interleukin-6 (IL-6), IL-1 and tumor necrosis factor-α (TNF-α) expression in a concentration-dependent manner. In addition, we confirmed that IA inhibited the phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), IKKα phosphorylation and NF-κB activity induced by Ox-LDL. Overall, these findings define IA as a novel drug candidate for anti-atherosclerotic therapy.
authors: College of Medicine, Yangzhou University, Yangzhou 225001, Jiangsu, PR China; Medical and Pharmaceutical Institute, Yangzhou University, Yangzhou 225001, Jiangsu, PR China.
authors: Chang
authors: C
authors: Liu
authors: Medical and Pharmaceutical Institute, Yangzhou University, Yangzhou 225001, Jiangsu, PR China.
authors: Junxian
authors: J
authors: Zhao
authors: College of Medicine, Yangzhou University, Yangzhou 225001, Jiangsu, PR China.
authors: YunXing
authors: Y
authors: Liu
authors: Suzhou Vocational Health College, Suzhou 215009, Jiangsu, PR China.
authors: Yi
authors: Y
authors: Huang
authors: College of Medicine, Yangzhou University, Yangzhou 225001, Jiangsu, PR China.
authors: Yanjun
authors: Y
authors: Shen
authors: Medical and Pharmaceutical Institute, Yangzhou University, Yangzhou 225001, Jiangsu, PR China.
authors: Juan
authors: J
authors: Wang
authors: Medical and Pharmaceutical Institute, Yangzhou University, Yangzhou 225001, Jiangsu, PR China; Chinese Medicine Hospital of Yangzhou City, Yangzhou 225009, Jiangsu, PR China; Institute of Clinical Chinese Tradition Medicine, Yangzhou University, 225001, Jiangsu, PR China. Electronic address: ysun@yzu.edu.cn.
authors: Weidong
authors: W
authors: Sun
authors: College of Medicine, Yangzhou University, Yangzhou 225001, Jiangsu, PR China; Medical and Pharmaceutical Institute, Yangzhou University, Yangzhou 225001, Jiangsu, PR China. Electronic address: zyykjc@sina.com.
authors: Yun
authors: Y
authors: Sun
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000097:blood; D059305:Diet, High-Fat; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D001057:Apolipoproteins E; D016207:Cytokines; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D014315:Triterpenes; C468850:ilexgenin A; C099252:oxidized low density lipoprotein; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051550:I-kappa B Kinase
keywords: Atherosclerosis; Ilexgenin A; Inflammation; Lipid disorder; Oxidized low-density lipoprotein; THP-1