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Journal of Integrative Medicine ›› 2014, Vol. 12 ›› Issue (2): 76-85.doi: 10.1016/S2095-4964(14)60013-3

• Review • Previous Articles     Next Articles

Natural modulators of liver X receptors

Cheng Huang   

  1. School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
  • Received:2014-01-11 Accepted:2014-02-24 Online:2014-03-10 Published:2014-03-15

Nuclear receptor transcription factors are ligand-activated proteins that control various biological events from cell growth and development to lipid metabolism, and energy and glucose homeostasis. Nuclear receptors are important drug targets for metabolic diseases. Liver X receptors (LXRs) are nuclear receptor transcription factors that play essential roles in regulation of cholesterol, triglyceride, fatty acid, and glucose homeostasis. LXR-deficient mice have shown the association of LXR-signaling pathway dysfunction with several human pathologies including atherosclerosis, hyperlipidemia, Alzheimer’s disease and cancer. Thus, LXRs are promising pharmacological targets for these diseases. Synthetic LXR agonists may lower cholesterol, but increase triglyceride and induce fatty liver. The naturally occurring LXR ligands, with moderate activity, may serve as nutraceuticals for prevention or treatment of the disorders, while minimizing potential side effects. In this review, recent advances in natural LXR modulators are summarized including agonist, antagonist and the modulator of LXR pathway.

Key words: Liver X receptors, Agonist, Antagonist, Atherosclerosis, Steatosis, Hyperlipidemia, Hypercholesterolemia, Hypertriglyceridemia, Nutraceuticals, Reviews

[1] Willy PJ, Umesono K, Ong ES, Evans RM, Heyman RA, Mangelsdorf DJ . LXR, a nuclear receptor that defines a distinct retinoid response pathway[J]. Genes Dev, 1995,9(9):1033-1045
doi: 10.1101/gad.9.9.1033
[2] Shinar DM, Endo N, Rutledge SJ, Vogel R, Rodan GA, Schmidt A . NER, a new member of the gene family encoding the human steroid-hormone nuclear receptor[J]. Gene, 1994,147(2):273-276
doi: 10.1016/0378-1119(94)90080-9 pmid: 7926814
[3] Repa JJ, Mangelsdorf DJ . The role of orphan nuclear receptors in the regulation of cholesterol homeostasis[J]. Annu Rev Cell Dev Biol, 2000,16:459-481
doi: 10.1021/jo901398w pmid: 11031244
[4] Edwards PA, Kennedy MA, Mak PA . LXRs; oxysterol-activated nuclear receptors that regulate genes controlling lipid homeostasis[J]. Vascul Pharmacol, 2002,38(4):249-256
doi: 10.1016/S1537-1891(02)00175-1
[5] Janowski BA, Willy PJ, Devi TR, Falck JR, Mangelsdorf DJ . An oxysterol signalling pathway mediated by the nuclear receptor LXRα[J]. Nature, 1996,383(6602):728-731
doi: 10.1038/383728a0 pmid: 8878485
[6] Repa JJ, Berge KE, Pomajzl C, Richardson JA, Hobbs H, Mangelsdorf DJ . Regulation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 by the liver X receptors α and β[J]. J Biol Chem, 2002,277(21):18793-18800
doi: 10.1074/jbc.M109927200
[7] Viennois E, Pommier AJ, Mouzat K, Oumeddour A, El Hajjaji FZ, Dufour J, Caira F, Volle DH, Baron S, Lobaccaro JM. Targeting liver X receptors in human health: deadlock or promising trail? Expert Opin Ther Targets. 2011; 15(2):219-232.
doi: 10.1517/14728222.2011.547853 pmid: 21204733
[8] Viennois E, Mouzat K, Dufour J, Morel L, Lobaccaro JM, Baron S. Selective liver X receptor modulators (SLiMs): What use in human health? . Mol Cell Endocrinol. 2012; 351(2):129-141.
doi: 10.1016/j.mce.2011.08.036
[9] Zelcer N, Tontonoz P . Liver X receptors as integrators of metabolic and inflammatory signaling[J]. J Clin Invest, 2006,116(3):607-614
doi: 10.1172/JCI27883 pmid: 16511593
[10] Li X, Zhang S, Blander G, Tse JG, Krieger M, Guarente L . SIRT1 deacetylates and positively regulates the nuclear receptor LXR[J]. Mol Cell, 2007,28(1):91-106
doi: 10.1016/j.molcel.2007.07.032 pmid: 17936707
[11] Hu X, Li SZ, Wu J, Xia CS, Lala DS . Liver X receptors interact with corepressors to regulate gene expression[J]. Mol Endocrinol, 2003,17(6):1019-1026
doi: 10.1210/me.2002-0399 pmid: 12663743
[12] Codina A, Love JD, Li Y, Lazar MA, Neuhaus D, Schwabe JW . Structural insights into the interaction and activation of histone deacetylase 3 by nuclear receptor corepressors[J]. Proc Natl Acad Sci U S A, 2005,102(17):6009-6014
doi: 10.1073/pnas.0500299102
[13] Peet DJ, Turley SD, Ma W, Janowski BA, Lobaccaro JM, Hammer RE, Mangelsdorf DJ . Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXRα[J]. Cell, 1998,93(5):693-704
doi: 10.1016/S0092-8674(00)81432-4
[14] Volle DH, Repa JJ, Mazur A, Cummins CL, Val P, Henry-Berger J, Caira F, Veyssiere G, Mangelsdorf DJ, Lobaccaro JM . Regulation of the aldo-keto reductase gene akr1b7 by the nuclear oxysterol receptor LXRα(liver X receptor-α) in the mouse intestine: putative role of LXRs in lipid detoxification processes[J]. Mol Endocrinol, 2004,18(4):888-898
doi: 10.1210/me.2003-0338
[15] Cha JY, Repa JJ . The liver X receptor(LXR) and hepatic lipogenesis — The carbohydrate-response element-binding protein is a target gene of LXR[J]. J Biol Chem, 2007,282(1):743-751
doi: 10.1074/jbc.M605023200
[16] Leoni V, Caccia C . Oxysterols as biomarkers in neurodegenerative diseases[J]. Chem Phys Lipids, 2011,164(6):515-524
doi: 10.1016/j.chemphyslip.2011.04.002 pmid: 21515244
[17] Huang TH, Razmovski-Naumovski V, Salam NK, Duke RK, Tran VH, Duke CC, Roufogalis BD . A novel LXR-α activator identified from the natural product Gynostemma pentaphyllum[J]. Biochem Pharmacol, 2005,70(9):1298-1308
doi: 10.1016/j.bcp.2005.07.033 pmid: 16154115
[18] Li XL, Yeh V, Molteni V . Liver X receptor modulators: a review of recently patented compounds(2007-2009)[J]. Expert Opin Ther Pat, 2010,20(4):535-562
doi: 10.1517/13543771003621269 pmid: 2030245120302451
[19] Loren J, Huang ZH, Laffitte BA, Molteni V . Liver X receptor modulators: a review of recently patented compounds(2009-2012)[J]. Expert Opin Ther Pat, 2013,23(10):1317-1335
doi: 10.1517/13543776.2013.814640 pmid: 23826715
[20] Schultz JR, Tu H, Luk A, Repa JJ, Medina JC, Li L, Schwendner S, Wang S, Thoolen M, Mangelsdorf DJ, Lustig KD, Shan B . Role of LXRs in control of lipogenesis[J]. Genes Dev, 2000,14(22):2831-2838
doi: 10.1101/gad.850400 pmid: 11090131
[21] Collins JL, Fivush AM, Watson MA, Galardi CM, Lewis MC, Moore LB, Parks DJ, Wilson JG, Tippin TK, Binz JG, Plunket KD, Morgan DG, Beaudet EJ, Whitney KD, Kliewer SA, Willson TM . Identification of a nonsteroidal liver X receptor agonist through parallel array synjournal of tertiary amines[J]. J Med Chem, 2002,45(10):1963-1966
doi: 10.1021/jm0255116
[22] Laurencikiene J, Ryden M . Liver X receptors and fat cell metabolism[J]. Int J Obes, 2012,36(12):1494-1502
doi: 10.1038/ijo.2012.21 pmid: 22370853
[23] Cummins CL, Volle DH, Zhang Y , McDonald JG, Sion B, Lefran?ois-Martinez AM, Caira F, Veyssière G, Mangelsdorf DJ, Lobaccaro JM.Liver X receptors regulate adrenal cholesterol balance[J]. J Clin Invest, 2006,116(7):1902-1912
doi: 10.1172/JCI28400 pmid: 1483175
[24] Mascrez B, Ghyselinck NB, Watanabe M, Annicotte JS, Chambon P, Auwerx J, Mark M . Ligand-dependent contribution of RXRβ to cholesterol homeostasis in Sertoli cells[J]. EMBO Rep, 2004,5(3):285-290
doi: 10.1038/sj.embor.7400094 pmid: 14993927
[25] Robertson KM, Schuster GU, Steffensen KR, Hovatta O, Meaney S, Hultenby K, Johansson LC, Svechnikov K , S?der O, Gustafsson JA.The liver X receptor-β is essential for maintaining cholesterol homeostasis in the testis[J]. Endocrinology, 2005,146(6):2519-2530
doi: 10.1210/en.2004-1413
[26] Volle DH, Mouzat K, Duggavathi R, Siddeek B, Déchelotte P, Sion B, Veyssière G, Benahmed M, Lobaccaro JM . Multiple roles of the nuclear receptors for oxysterols liver X receptor to maintain male fertility[J]. Mol Endocrinol, 2007,21(5):1014-1027
doi: 10.1210/me.2006-0277
[27] Mouzat K, Prod’homme M, Volle DH, Sion B, Déchelotte P, Gauthier K, Vanacker JM, Lobaccaro JM . Oxysterol nuclear receptor LXRβ regulates cholesterol homeostasis and contractile function in mouse uterus[J]. J Biol Chem, 2007,282(7):4693-4701
doi: 10.1074/jbc.M606718200
[28] Mouzat K, Volat F, Baron S, Alves G, Pommier AJ, Volle DH, Marceau G , DeHaze A, Déchelotte P, Duggavathi R, Caira F, Lobaccaro JM.Absence of nuclear receptors for oxysterols liver X receptor induces ovarian hyperstimulation syndrome in mice[J]. Endocrinology, 2009,150(7):3369-3375
doi: 10.1210/en.2008-1519
[29] Mouzat K, Mercier E, Polge A, Evrard A, Baron S, Balducchi JP, Brouillet JP, Lumbroso S, Gris JC . A common polymorphism in NR1H2(LXRβ) is associated with preeclampsia[J]. BMC Med Genet, 2011,12:145
doi: 10.1186/1471-2350-12-145 pmid: 22029530
[30] Lo Sasso G, Murzilli S, Salvatore L , D’Errico I, Petruzzelli M, Conca P, Jiang ZY, Calabresi L, Parini P, Moschetta A.Intestinal specific LXR activation stimulates reverse cholesterol transport and protects from atherosclerosis[J]. Cell Metab, 2010,12(2):187-193
doi: 10.1016/j.cmet.2010.07.002
[31] Joseph SB , McKilligin E, Pei L, Watson MA, Collins AR, Laffitte BA, Chen M, Noh G, Goodman J, Hagger GN, Tran J, Tippin TK, Wang X, Lusis AJ, Hsueh WA, Law RE, Collins JL, Willson TM, Tontonoz P. Synthetic LXR ligand inhibits the development of atherosclerosis in mice[J]. Proc Natl Acad Sci U S A, 2002,99(11):7604-7609
doi: 10.1073/pnas.112059299 pmid: 12032330
[32] Im SS, Osborne TF . Liver X receptors in atherosclerosis and inflammation[J]. Circ Res, 2011,108(8):996-1001
doi: 10.1161/CIRCRESAHA.110.226878 pmid: 21493922
[33] Laffitte BA, Chao LC, Li J, Walczak R, Hummasti S, Joseph SB, Castrillo A, Wilpitz DC, Mangelsdorf DJ, Collins JL, Saez E, Tontonoz P . Activation of liver X receptor improves glucose tolerance through coordinate regulation of glucose metabolism in liver and adipose tissue[J]. Proc Natl Acad Sci U S A, 2003,100(9):5419-5424
doi: 10.1073/pnas.0830671100
[34] Kase ET, Wensaas AJ, Aas V , H?jlund K, Levin K, Thoresen GH, Beck-Nielsen H, Rustan AC, Gaster M.Skeletal muscle lipid accumulation in type 2 diabetes may involve the liver X receptor pathway[J]. Diabetes, 2005,54(4):1108-1115
doi: 10.2337/diabetes.54.4.1108 pmid: 15793250
[35] Koldamova RP, Lefterov IM, Staufenbiel M, Wolfe D, Huang S, Glorioso JC, Walter M, Roth MG, Lazo JS . The liver X receptor ligand T0901317 decreases amyloid β production in vitro and in a mouse model of Alzheimer’s disease[J]. J Biol Chem, 2005,280(6):4079-4088
doi: 10.1074/jbc.M411420200
[36] Zelcer N, Khanlou N, Clare R, Jiang Q, Reed-Geaghan EG, Landreth GE, Vinters HV, Tontonoz P . Attenuation of neuroinflammation and Alzheimer’s disease pathology by liver x receptors[J]. Proc Natl Acad Sci U S A, 2007,104(25):10601-10606
doi: 10.1073/pnas.0701096104 pmid: 17563384
[37] Fitz NF, Cronican A, Pham T, Fogg A, Fauq AH, Chapman R, Lefterov I, Koldamova R . Liver X receptor agonist treatment ameliorates amyloid pathology and memory deficits caused by high-fat diet in app23 mice[J]. J Neurosci, 2010,30(20):6862-6872
doi: 10.1523/JNEUROSCI.1051-10.2010
[38] Kang JH, Rivest S . Lipid metabolism and neuroinflammation in Alzheimer’s disease: a role for liver X receptors[J]. Endocr Rev, 2012,33(5):715-746
doi: 10.1210/er.2011-1049 pmid: 22766509
[39] De Boussac H, Alioui A, Viennois E, Dufour J, Trousson A, Vega A, Guy L, Volle DH, Lobaccaro JM, Baron S . Oxysterol receptors and their therapeutic applications in cancer conditions[J]. Expert Opin Ther Targets, 2013,17(9):1029-1038
doi: 10.1517/14728222.2013.820708 pmid: 23875732
[40] Fukuchi J, Kokontis JM, Hiipakka RA, Chuu CP, Liao ST . Antiproliferative effect of liver X receptor agonists on LNCaP human prostate cancer cells[J]. Cancer Res, 2004,64(21):7686-7689
doi: 10.1158/0008-5472.CAN-04-2332 pmid: 15520170
[41] Pommier AJ, Alves G, Viennois E, Bernard S, Communal Y, Sion B, Marceau G, Damon C, Mouzat K, Caira F, Baron S, Lobaccaro JM . Liver X receptor activation downregulates AKT survival signaling in lipid rafts and induces apoptosis of prostate cancer cells[J]. Oncogene, 2010,29(18):2712-2723
doi: 10.1038/onc.2010.30
[42] Fukuchi J, Hiipakka RA, Kokontis JM, Hsu S, Ko AL, Fitzgerald ML, Liao S . Androgenic suppression of ATP-binding cassette transporter A1 expression in LNCaP human prostate cancer cells[J]. Cancer Res, 2004,64(21):7682-7685
doi: 10.1158/0008-5472.CAN-04-2647
[43] Pommier AJ, Dufour J, Alves G, Viennois E, De Boussac H, Trousson A, Volle DH, Caira F, Val P, Arnaud P, Lobaccaro JM, Baron S . Liver x receptors protect from development of prostatic intra-epithelial neoplasia in mice[J]. PLoS Genet, 2013,9:e1003483
doi: 10.1371/journal.pgen.1003483 pmid: 23675307
[44] Schroepfer GJ , Jr.Oxysterols: modulators of cholesterol metabolism and other processes[J]. Physiol Rev, 2000,80(1):361-554
doi: 10.1152/physrev.2000.80.1.361
[45] Lehmann JM, Kliewer SA, Moore LB, Smith-Oliver TA, Oliver BB, Su JL, Sundseth SS, Winegar DA, Blanchard DE, Spencer TA, Willson TM . Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway[J]. J Biol Chem, 1997,272(6):3137-3140
doi: 10.1074/jbc.272.6.3137 pmid: 9013544
[46] Beltowski J, Semczuk A . Liver X receptor(LXR) and the reproductive system — a potential novel target for therapeutic intervention[J]. Pharmacol Rep, 2010,62(1):15-27
[47] Schaffer S, Tandon R, Zipse H, Siess W, Schmidt A, Jamasbi J, Karshovska E, Steglich W, Lorenz R . Stereo specific platelet inhibition by the natural LXR agonist 22(R)-OH-cholesterol and its fluorescence labelling with preserved bioactivity and chiral handling in macrophages[J]. Biochem Pharmacol, 2013,86(2):279-285
doi: 10.1016/j.bcp.2013.04.024
[48] Okabe A, Urano Y, Itoh S, Suda N, Kotani R, Nishimura Y, Saito Y, Noguchi N . Adaptive responses induced by 24S-hydroxycholesterol through liver X receptor pathway reduce 7-ketocholesterol-caused neuronal cell death[J]. Redox Biol, 2013,2:28-35
[49] Forman BM, Ruan B, Chen J, Schroepfer GJ Jr, Evans RM . The orphan nuclear receptor LXRα is positively and negatively regulated by distinct products of mevalonate metabolism[J]. Proc Natl Acad Sci U S A, 1997,94(20):10588-10593
doi: 10.1073/pnas.94.20.10588
[50] Ruan B, Wilson WK, Schroepfer GJ Jr . An alternative synjournal of 4,4-dimethyl-5α-cholesta-8,14,24-trien-3β-ol, an intermediate in sterol biosynjournal and a reported activator of meiosis and of nuclear orphan receptor LXRα[J]. Bioorg Med Chem Lett, 1998,8(3):233-236
doi: 10.1016/S0960-894X(98)00016-X
[51] Yang C , McDonald JG, Patel A, Zhang Y, Umetani M, Xu F, Westover EJ, Covey DF, Mangelsdorf DJ, Cohen JC, Hobbs HH.Sterol intermediates from cholesterol biosynthetic pathway as liver X receptor ligands[J]. J Biol Chem, 2006,281(38):27816-27826
doi: 10.1074/jbc.M603781200 pmid: 16857673
[52] Song C, Hiipakka RA, Liao SS . Selective activation of liver X receptor α by 6α-hydroxy bile acids and analogs[J]. Steroids, 2000,65(8):423-427
doi: 10.1016/S0039-128X(00)00127-6
[53] Hessvik NP, Bakke SS, Smith R, Ravna AW, Sylte I, Rustan AC, Thoresen GH, Kase ET . The liver X receptor modulator 22(S)-hydroxycholesterol exerts cell-type specific effects on lipid and glucose metabolism[J]. J Steroid Biochem Mol Biol, 2012,128(3-5):154-164
doi: 10.1016/j.jsbmb.2011.10.006
[54] Berrodin TJ, Shen Q, Quinet EM, Yudt MR, Freedman LP, Nagpal S . Identification of 5α,6α-epoxycholesterol as a novel modulator of liver X receptor activity[J]. Mol Pharmacol, 2010,78(6):1046-1058
doi: 10.1124/mol.110.065193
[55] Song C, Hiipakka RA, Liao SS . Auto-oxidized cholesterol sulfates are antagonistic ligands of liver X receptors: implications for the development and treatment of atherosclerosis[J]. Steroids, 2001,66(6):473-479
doi: 10.1016/S0039-128X(00)00239-7
[56] Ou J, Tu H, Shan B, Luk A , DeBose-Boyd RA, Bashmakov Y, Goldstein JL, Brown MS.Unsaturated fatty acids inhibit transcription of the sterol regulatory element-binding protein-1c(SREBP-1c) gene by antagonizing ligand-dependent activation of the LXR[J]. Proc Natl Acad Sci U S A, 2001,98(11):6027-6032
doi: 10.1073/pnas.111138698
[57] Yoshikawa T, Shimano H, Yahagi N, Ide T, Amemiya-Kudo M, Matsuzaka T, Nakakuki M, Tomita S, Okazaki H, Tamura Y, Iizuka Y, Ohashi K, Takahashi A, Sone H, Osuga Ji J, Gotoda T, Ishibashi S, Yamada N . Polyunsaturated fatty acids suppress sterol regulatory element-binding protein 1c promoter activity by inhibition of liver X receptor(LXR) binding to LXR response elements[J]. J Biol Chem, 2002,277(3):1705-1711
doi: 10.1074/jbc.M105711200
[58] Zhuang J, Zhang H, Zhou R, Chen L, Chen J, Shen X . Regulation of prostaglandin F2α against β amyloid clearance and its inflammation induction through LXR/RXR heterodimer antagonism in microglia[J]. Prostaglandins Other Lipid Mediat, 2013,106:45-52
doi: 10.1016/j.prostaglandins.2013.09.002
[59] Lee JM, Gang GT, Kim DK, Kim YD, Koo SH, Lee CH, Choi HS . Ursodeoxycholic acid inhibits liver X receptor α-mediated hepatic lipogenesis via induction of the nuclear corepressor SMILE[J]. J Biol Chem, 2014,289(2):1079-1091
doi: 10.1074/jbc.M113.491522
[60] Qin Y, Dalen KT, Gustafsson JA, Nebb HI . Regulation of hepatic fatty acid elongase 5 by LXR α-SREBP-1c[J]. Biochim Biophys Acta, 2009,1791(2):140-147
doi: 10.1016/j.bbalip.2008.12.003
[61] Plat J, Nichols JA, Mensink RP . Plant sterols and stanols: effects on mixed micellar composition and LXR(target gene) activation[J]. J Lipid Res, 2005,46(11):2468-2476
doi: 10.1194/jlr.M500272-JLR200
[62] Plat J, Mensink RP . Increased intestinal ABCA1 expression contributes to the decrease in cholesterol absorption after plant stanol consumption[J]. FASEB J, 2002,16(10):1248-1253
doi: 10.1096/fj.01-0718hyp
[63] Pl?sch T, Kruit JK, Bloks VW, Huijkman NC, Havinga R, Duchateau GS, Lin Y, Kuipers F . Reduction of cholesterol absorption by dietary plant sterols and stanols in mice is independent of the Abcg5/8 transporter[J]. J Nutr, 2006,136(8):2135-2140
doi: 10.1093/jn/136.8.2135
[64] Traves PG, Hortelano S, Zeini M, Chao TH, Lam T, Neuteboom ST, Theodorakis EA, Palladino MA, Castrillo A, Bosca L . Selective activation of liver X receptors by acanthoic acid-related diterpenes[J]. Mol Pharmacol, 2007,71(6):1545-1553
doi: 10.1124/mol.106.031906 pmid: 17329499
[65] Jayasuriya H, Herath KB, Ondeyka JG, Guan Z, Borris RP , Tiwari S, de Jong W, Chavez F, Moss J, Stevenson DW, Beck HT, Slattery M, Zamora N, Schulman M, Ali A, Sharma N, MacNaul K, Hayes N, Menke JG, Singh SB. Diterpenoid, steroid, and triterpenoid agonists of liver X receptors from diversified terrestrial plants and marine sources[J]. J Nat Prod, 2005,68(8):1247-1252
doi: 10.1021/np050182g
[66] Hoang MH, Jia Y, Jun HJ, Lee JH, Lee BY, Lee SJ . Fucosterol is a selective liver X receptor modulator that regulates the expression of key genes in cholesterol homeostasis in macrophages, hepatocytes, and intestinal cells[J]. J Agric Food Chem, 2012,60(46):11567-11575
doi: 10.1021/jf3019084
[67] Kaneko E, Matsuda M, Yamada Y, Tachibana Y, Shimomura I, Makishima M . Induction of intestinal ATP-binding cassette transporters by a phytosterol-derived liver X receptor agonist[J]. J Biol Chem, 2003,278(38):36091-36098
doi: 10.1074/jbc.M304153200
[68] Singh SB, Ondeyka JG, Liu W, Chen S, Chen TS, Li X, Bouffard A, Dropinski J, Jones AB , McCormick S, Hayes N, Wang J, Sharma N, Macnaul K, Hernandez M, Chao YS, Baffic J, Lam MH, Burton C, Sparrow CP, Menke JG.Discovery and development of dimeric podocarpic acid leads as potent agonists of liver X receptor with HDL cholesterol raising activity in mice and hamsters[J]. Bioorg Med Chem Lett, 2005,15(11):2824-2828
doi: 10.1016/j.bmcl.2005.03.100
[69] Jung CG, Horike H, Cha BY, Uhm KO, Yamauchi R, Yamaguchi T, Hosono T, Iida K, Woo JT, Michikawa M . Honokiol increases ABCA1 expression level by activating retinoid X receptor β[J]. Biol Pharm Bull, 2010,33(7):1105-1111
doi: 10.1248/bpb.33.1105 pmid: 20606297
[70] Kotani H, Tanabe H, Mizukami H, Makishima M, Inoue M . Identification of a naturally occurring rexinoid, honokiol, that activates the retinoid X receptor[J]. J Nat Prod, 2010,73(8):1332-1336
doi: 10.1021/np100120c
[71] Lin HR . Paeoniflorin acts as a liver X receptor agonist[J]. J Asian Nat Prod Res, 2013,15(1):35-45
doi: 10.1080/10286020.2012.742510 pmid: 23281636
[72] Jun HJ, Hoang MH, Lee JW, Yaoyao J, Lee JH, Lee DH, Lee HJ, Seo WD, Hwang BY, Lee SJ . Iristectorigenin B isolated from Belamcanda chinensis is a liver X receptor modulator that increases ABCA1 and ABCG1 expression in macrophage RAW 264.7 cells[J]. Biotechnol Lett, 2012,34(12):2213-2221
doi: 10.1007/s10529-012-1036-y
[73] Hoang MH, Jia Y, Jun HJ, Lee JH, Lee DH, Hwang BY, Kim WJ, Lee HJ, Lee SJ . Ethyl 2,4,6-trihydroxybenzoate is an agonistic ligand for liver X receptor that induces cholesterol efflux from macrophages without affecting lipid accumulation in HepG2 cells[J]. Bioorg Med Chem Lett, 2012,22(12):4094-4099
doi: 10.1016/j.bmcl.2012.04.071
[74] Jia Y, Hoang MH, Jun HJ, Lee JH, Lee SJ . Cyanidin, a natural flavonoid, is an agonistic ligand for liver X receptor α and β and reduces cellular lipid accumulation in macrophages and hepatocytes[J]. Bioorg Med Chem Lett, 2013,23(14):4185-4190
doi: 10.1016/j.bmcl.2013.05.030
[75] Jun HJ, Hoang MH, Yeo SK, Jia Y, Lee SJ . Induction of ABCA1 and ABCG1 expression by the liver X receptor modulator cineole in macrophages[J]. Bioorg Med Chem Lett, 2013,23(2):579-583
doi: 10.1016/j.bmcl.2012.11.012 pmid: 23246324
[76] Bramlett KS, Houck KA, Borchert KM, Dowless MS, Kulanthaivel P, Zhang Y, Beyer TP, Schmidt R, Thomas JS, Michael LF, Barr R, Montrose C, Eacho PI, Cao G, Burris TP . A natural product ligand of the oxysterol receptor, liver X receptor[J]. J Pharmacol Exp Ther, 2003,307(1):291-296
doi: 10.1124/jpet.103.052852 pmid: 12893846
[77] Ondeyka JG, Jayasuriya H, Herath KB, Guan Z, Schulman M, Collado J, Dombrowski AW, Kwon SS , McCallum C, Sharma N, MacNaul K, Hayes N, Menke JG, Singh SB. Steroidal and triterpenoidal fungal metabolites as ligands of liver X receptors[J]. J Antibiot, 2005,58(9):559-565
doi: 10.1038/ja.2005.76 pmid: 16320760
[78] Herath K, Jayasuriya H, Ondeyka JG, Guan Z, Borris RP, Stijfhoorn E, Stevenson D, Wang J, Sharma N, Macnaul K, Menke JG, Ali A, Schulman MJ, Singh SB . Guttiferone I, a new prenylated benzophenone from Garcinia humilis as a liver X receptor ligand[J]. J Nat Prod, 2005,68(4):617-619
doi: 10.1021/np050045j
[79] Tamehiro N, Sato Y, Suzuki T, Hashimoto T, Asakawa Y, Yokoyama S, Kawanishi T, Ohno Y, Inoue K, Nagao T, Nishimaki-Mogami T . Riccardin C: a natural product that functions as a liver X receptor(LXR) α agonist and an LXRβ antagonist[J]. FEBS Lett, 2005,579(24):5299-5304
doi: 10.1016/j.febslet.2005.08.054
[80] Goldwasser J, Cohen PY, Yang E, Balaguer P, Yarmush ML, Nahmias Y . Transcriptional regulation of human and rat hepatic lipid metabolism by the grapefruit flavonoid naringenin: role of PPARα, PPARγ and LXRα[J]. PLoS One, 2010,5:e12399
doi: 10.1371/journal.pone.0012399
[81] González-Granillo M, Steffensen KR, Granados O, Torres N, Korach-André M, Ortíz V, Aguilar-Salinas C, Jakobsson T , Díaz-Villase?or A, Loza-Valdes A, Hernandez-Pando R, Gustafsson J, Tovar AR.Soy protein isoflavones differentially regulate liver X receptor isoforms to modulate lipid metabolism and cholesterol transport in the liver and intestine in mice[J]. Diabetologia, 2012,55(9):2469-2478
doi: 10.1007/s00125-012-2599-9
[82] Hoang MH, Jia Y, Jun HJ, Lee JH, Hwang KY, Choi DW, Um SJ, Lee BY, You SG, Lee SJ . Taurine is a liver X receptor-α ligand and activates transcription of key genes in the reverse cholesterol transport without inducing hepatic lipogenesis[J]. Mol Nutr Food Res, 2012,56(6):900-911
doi: 10.1002/mnfr.201100611
[83] Sheng X, Wang M, Lu M, Xi B, Sheng H, Zang YQ . Rhein ameliorates fatty liver disease through negative energy balance, hepatic lipogenic regulation, and immunomodulation in diet-induced obese mice[J]. Am J Physiol Endocrinol Metab, 2011,300(5):E886-E893
doi: 10.1152/ajpendo.00332.2010
[84] Kanaya N, Kubo M, Liu Z, Chu P, Wang C, Yuan YC, Chen S . Protective effects of white button mushroom(Agaricus bisporus) against hepatic steatosis in ovariectomized mice as a model of postmenopausal women[J]. PLoS One, 2011,6:e26654
doi: 10.1371/journal.pone.0026654
[85] Fan S, Zhang Y, Hu N, Sun Q, Ding X, Li G, Zheng B, Gu M, Huang F, Sun YQ, Zhou Z, Lu X, Huang C, Ji G . Extract of Kuding tea prevents high-fat diet-induced metabolic disorders in C57BL/6 mice via liver X receptor(LXR) β antagonism[J]. PLoS One, 2012,7:e51007
doi: 10.1371/journal.pone.0051007
[86] Fan S, Guo L, Zhang Y, Sun Q, Yang B, Huang C . Okra polysaccharide improves metabolic disorders in high-fat diet-induced obese C57BL/6 mice[J]. Mol Nutr Food Res, 2013,57(11):2075-2078
doi: 10.1002/mnfr.201300054 pmid: 23894043
[87] Kim KH, Choi SH, Lee TS, Oh WK, Kim DS, Kim JB . Selective LXRα inhibitory effects observed in plant extracts of MEH184(Parthenocissua tricuspidata) and MEH185(Euscaphis japonica)[J]. Biochem Biophys Res Commun, 2006,349(2):513-518
doi: 10.1016/j.bbrc.2006.08.092
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