Isoliquiritigenin Attenuates Atherogenesis in Apolipoprotein E-Deficient Mice

被引:29
作者
Du, Fen [1 ]
Gesang, Quzhen [1 ,2 ]
Cao, Jia [1 ]
Qian, Mei [1 ]
Ma, Li [1 ]
Wu, Dongfang [3 ]
Yu, Hong [1 ]
机构
[1] Wuhan Univ, Hubei Prov Key Lab Dev Originated Dis, Dept Biochem & Mol Biol, Sch Basic Med Sci, 185 Donghu Rd,Bldg 2,2-209, Wuhan 430071, Peoples R China
[2] Tibet Univ, Coll Med, Lhasa 850000, Peoples R China
[3] Wuhan Univ, Dept Pharm, Zhongnan Hosp, Wuhan 430071, Peoples R China
基金
中国国家自然科学基金;
关键词
isoliquiritigenin; atherosclerosis; cholesterol flux; anti-inflammation; anti-oxidation; ADIPOSE-TISSUE INFLAMMATION; MACROPHAGE-GENE-EXPRESSION; CORONARY-ARTERY-DISEASE; X-RECEPTOR-ALPHA; CARDIOVASCULAR-DISEASE; PPAR-GAMMA; CHOLESTEROL TRANSPORTERS; REDUCES ATHEROSCLEROSIS; OXIDATIVE STRESS; KNOCKOUT MICE;
D O I
10.3390/ijms17111932
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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(-/-)) miice. Firstly, we determined that ISL reduced the mRNA levels of inflammatory factors interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), 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 (PPAR gamma) 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-alpha, 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 as SRBI, ABCA1, ABCG8, PPAR gamma, and FASN) 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 PPAR gamma-dependent signaling.
引用
收藏
页数:14
相关论文
共 48 条
[1]   Superoxide dismutases-a review of the metal-associated mechanistic variations [J].
Abreu, Isabel A. ;
Cabelli, Diane E. .
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, 2010, 1804 (02) :263-274
[2]  
[Anonymous], 2016, EVID BASED COMPLEMEN, DOI DOI 10.1016/J.JAMDA.2016.06.001
[3]   A PPARγ-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis [J].
Chawla, A ;
Boisvert, WA ;
Lee, CH ;
Laffitte, BA ;
Barak, Y ;
Joseph, SB ;
Liao, D ;
Nagy, L ;
Edwards, PA ;
Curtiss, LK ;
Evans, RM ;
Tontonoz, P .
MOLECULAR CELL, 2001, 7 (01) :161-171
[4]   PPAR-γ dependent and independent effects on macrophage-gene expression in lipid metabolism and inflammation [J].
Chawla, A ;
Barak, Y ;
Nagy, L ;
Liao, D ;
Tontonoz, P ;
Evans, RM .
NATURE MEDICINE, 2001, 7 (01) :48-52
[5]   MicroRNA-155 Deficiency Results in Decreased Macrophage Inflammation and Attenuated Atherogenesis in Apolipoprotein E-Deficient Mice [J].
Du, Fen ;
Yu, Fang ;
Wang, Yuzhen ;
Hui, Yvonne ;
Carnevale, Kevin ;
Fu, Mingui ;
Lu, Hong ;
Fan, Daping .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2014, 34 (04) :759-767
[6]   ABC transporters, atherosclerosis and inflammation [J].
Fitzgerald, Michael L. ;
Mujawar, Zahedi ;
Tamehiro, Norimasa .
ATHEROSCLEROSIS, 2010, 211 (02) :361-370
[7]   ABCG5 and ABCG8 are obligate heterodimers for protein trafficking and biliary cholesterol excretion [J].
Graf, GA ;
Yu, LQ ;
Li, WP ;
Gerard, R ;
Tuma, PL ;
Cohen, JC ;
Hobbs, HH .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (48) :48275-48282
[8]  
Hamblin M, 2009, ANTIOXID REDOX SIGN, V11, P1415, DOI [10.1089/ars.2008.2280, 10.1089/ARS.2008.2280]
[9]   Mechanisms of disease - Inflammation, atherosclerosis, and coronary artery disease [J].
Hansson, GK .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 352 (16) :1685-1695
[10]   Isoliquiritigenin is a potent inhibitor of NLRP3 inflammasome activation and diet-induced adipose tissue inflammation [J].
Honda, Hiroe ;
Nagai, Yoshinori ;
Matsunaga, Takayuki ;
Okamoto, Naoki ;
Watanabe, Yasuharu ;
Tsuneyama, Koichi ;
Hayashi, Hiroaki ;
Fujii, Isao ;
Ikutani, Masashi ;
Hirai, Yoshikatsu ;
Muraguchi, Atsushi ;
Takatsu, Kiyoshi .
JOURNAL OF LEUKOCYTE BIOLOGY, 2014, 96 (06) :1087-1100