title: Isoliquiritigenin Attenuates Atherogenesis in Apolipoprotein E-Deficient Mice.
abstract: Isoliquiritigenin (ISL) exhibits antioxidation and anti-inflammation activity. We sought to investigate the effects and mechanism of ISL on the development of atherosclerotic lesions in apolipoprotein E-deficient (apoE-/-) mice. Firstly, we determined that ISL reduced the mRNA levels of inflammatory factors interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and monocyte chemotactic protein-1 (MCP-1), while it increased the expression of several lipoprotein-related genes in peritoneal macrophages treated with lipopolysaccharide (LPS). ISL also enhanced peroxisome proliferator-activated receptor gamma (PPARγ) protein levels and reversed the changes of ATP-binding cassette transporter A (ABCA1) and cluster of differentiation 36 (CD36) in macrophages treated with oxidative low-density lipoprotein (ox-LDL). Then, in an in vivo study, female apoE-/-mice were fed a Western diet with ISL (0, 20, 100 mg/kg/day) added for 12 weeks. We found that ISL decreased the plasma cholesterol levels of very low-density lipoprotein (VLDL)/LDL, promoted plasma superoxide dismutase (SOD) and paraoxonase-1 (PON1) activities, and decreased plasma IL-6, TNF-α, and MCP-1 levels. Moreover, ISL significantly reduced the atherosclerotic lesions and hepatic steatosis in apoE-/-mice. In the liver, ISL altered the expression of several key genes (such asSRBI,ABCA1,ABCG8,PPARγ, andFASN) involving cholesterol-selective uptake and excretion into bile, triglyceride (TG) biosynthesis, and inflammation. These results suggest that the atheroprotective effects of ISL are due to the improvement of lipid metabolism, antioxidation, and anti-inflammation, which involve PPARγ-dependent signaling.
authors.affiliation: Department of Biochemistry and Molecular Biology, Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University School of Basic Medical Sciences, 185 Donghu Road, Bldg. 2, 2-209, Wuhan 430071, China. fen.du@whu.edu.cn.
authors.forename: Fen
authors.initials: F
authors.lastname: Du
authors.affiliation: Department of Biochemistry and Molecular Biology, Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University School of Basic Medical Sciences, 185 Donghu Road, Bldg. 2, 2-209, Wuhan 430071, China. gsqz123@163.com.|Medical College, Tibet University, Lhasa 850000, China. gsqz123@163.com.
authors.forename: Quzhen
authors.initials: Q
authors.lastname: Gesang
authors.affiliation: Department of Biochemistry and Molecular Biology, Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University School of Basic Medical Sciences, 185 Donghu Road, Bldg. 2, 2-209, Wuhan 430071, China. caojia1210@whu.edu.cn.
authors.forename: Jia
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Biochemistry and Molecular Biology, Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University School of Basic Medical Sciences, 185 Donghu Road, Bldg. 2, 2-209, Wuhan 430071, China. qianmei@whu.edu.cn.
authors.forename: Mei
authors.initials: M
authors.lastname: Qian
authors.affiliation: Department of Biochemistry and Molecular Biology, Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University School of Basic Medical Sciences, 185 Donghu Road, Bldg. 2, 2-209, Wuhan 430071, China. 2013203010022@whu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Pharmacy, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. dfwu2010@whu.edu.cn.
authors.forename: Dongfang
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University School of Basic Medical Sciences, 185 Donghu Road, Bldg. 2, 2-209, Wuhan 430071, China. yu.hong@whu.edu.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics*; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control; D015153:Blotting, Western; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D047188:Chalcones / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D064286:ATP Binding Cassette Transporter 1; D001057:Apolipoproteins E; D018955:CD36 Antigens; C491768:Ccl2 protein, mouse; D047188:Chalcones; D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D015850:Interleukin-6; D008070:Lipopolysaccharides; D047495:PPAR gamma; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D002784:Cholesterol; C040920:isoliquiritigenin
keywords: anti-inflammation; anti-oxidation; atherosclerosis; cholesterol flux; isoliquiritigenin