258
Views
37
CrossRef citations to date
0
Altmetric
Review

The farnesoid X receptor: a novel drug target?

, , &
Pages 1135-1148 | Published online: 24 Feb 2005

Bibliography

  • RUSSELL DW: The enzymes, regulation, and genetics of bile acid synthesis. Ann. Rev Biochem. (2003) 72:137–174.
  • MAKISHIMA M, OKAMOTO AY, REPA JJ et al.: Identification of a nuclear receptor for bile acids. Science (1999) 284(5418):1362–1365.
  • ••The identification of bile acids as FXRligands.
  • WANG H, CHEN J, HOLLISTER K, SOWERS LC, FORMAN BM: Endogenous bile acids are ligands for the nuclear receptor FXR/BAR. MM. Cell (1999) 3(5):543–553.
  • ••The identification of bile acids as FXRligands.
  • PARKS DJ, BLANCHARD SG, BLEDSOE RK et al.: Bile acids: natural for an orphan nuclear receptor. Science (1999) 284(5418):1365–1368.
  • ••The identification of bile acids as FXRligands.
  • LAFFITTE BA, KAST HR, CM et al.: Identification of the DNA binding specificity and potential target genes for the farnesoid X-activated receptor. J. Biol. Chem. (2000) 275(14):10638–10647.
  • CLAUDEL T, STURM E, DUEZ H et al: Bile acid-activated nuclear receptor FXR suppresses apolipoprotein A-I transcription via a negative FXR response element. J. Clio. Invest. (2002) 109(7):961–971.
  • •A link between bile acids and HDL and atherosclerosis.
  • BARBIER 0, TORRA IP, SIRVENT A al.: FXR induces the UGT2B4 enzyme in hepatocytes: a potential mechanism of negative feedback control of FXR activity. Gastroenterology (2003) 124(7):1926–1940.
  • ZHANG Y, KAST-WOELBERN HR, EDWARDS PA: Natural structural variants of the nuclear receptor farnesoid X receptor affect transcriptional activation. Biol. Chem. (2003) 278(1):104–110.
  • MAGLICH JM, SLUDER A, GUAN X et al.: Comparison of complete nuclear receptor sets from the human, Caenorhabditis elegans and Drosophila genomes. Genome Biol. (2001) 2(8):RESEARCH0029
  • OTTE K, KRANZ H, KOBER I et al.: Identification of farnesoid X receptor beta as a novel mammalian nuclear receptor sensing lanosterol. Mol. Cell. Biol. (2003) 23(3):864–872.
  • FORMAN BM, GOODE E, CHEN J et al.: Identification of a nuclear receptor that is activated by farnesol metabolites. Cell (1995) 81(5):687–693.
  • ••Cloning and first characterisation of FXR.
  • REPA JJ, MANGELSDORF DJ: Nuclearreceptor regulation of cholesterol and bile metabolism. Carr: Opin. Biotechnol (1999) 10(6):557–563.
  • CUI J, HEARD TS, YU J et at The amino acid residues asparagine 354 and isoleucine 372 of human farnesoid X receptor confer the receptor with high sensitivity to chenodeoxycholate. Biol. Chem. (2002) 277(29):25963–25969.
  • MALONEY PR, PARKS DJ, CD et al.: Identification of a chemical tool for the orphan nuclear receptor FXR. .1. Med. Chem. (2000) 43(16):2971–2974.
  • GUPTA S, STRAVITZ RT, DENT P, HYLEMON PB: Down-regulation of cholesterol 7a-hydroxylase (CYP7A1) gene expression by bile acids in primary rat hepatocytes is mediated by the c-Jun N-terminal kinase pathway. I. Biol. Chem. (2001) 276(19):15816–15822.
  • DUSSAULT I, BEARD R, LIN M et al: Identification of gene-selective modulators of the bile acid receptor FXR. Biol. Chem. (2003) 278(9):7027–7033.
  • ••Identification of the first FXR-specificmodulator.
  • PELLICCIARI R, FIORUCCI S, CAMAIONI E et al.: 6a-Ethyl-chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity. Med. Chem. (2002) 45(17):3569–3572.
  • DOWNES M, VERDECIA MA, ROECKER AJ et al.: A chemical, genetic, and structural analysis of the nuclear bile acid receptor FXR. MM. Cell (2003) 11(4):1079–1092.
  • MI LZ, DEVARAKONDA S, HARP JM et al.: Structural basis for bile acid binding and activation of the nuclear receptor FXR. Ma CO (2003) 11(4):1093–10100.
  • GROBER J, ZAGHINI I, FUJII H et al.: Identification of a bile acid-responsive element in the human ileal bile acid-binding protein gene. Involvement of the farnesoid receptor/9-cis-retinoic acid receptor heterodimer. J. Biol. Chem. (1999) 274(42):29749–29754.
  • KAST HR, NGUYEN CM, SINAL CJ et al.: Farnesoid x-activated receptor induces apolipoprotein c-ii transcription: a molecular mechanism linking plasma triglyceride levels to bile acids. MM. Endocrinol (2001) 15(10):1720–1728.
  • KASSAM A, MIAO B, YOUNG PR, MUKHERJEE R: Retinoid X receptor (RXR) agonist-induced antagonism of X receptor (FXR) activity due to absence of coactivator recruitment and decreased DNA binding. I Biol. Chem. (2003) 278(12):10028–10032.
  • BRAMLETT KS, YAO S, BURRIS TP: Correlation of farnesoid X receptor coactivator recruitment and cholesterol 7a-hydroxylase gene repression by bile acids. MM. Genet. Metab. (2000) 71(4):609–615.
  • PINEDA TORRA I, FREEDMAN LP, GARABEDIAN MJ: Identification of DRIP205 as a coactivator for the farnesoid receptor. Biol. Chem. (2004)
  • SINAL CJ, TOHKIN M, MIYATA M et al.: Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis. Cell (2000) 102(6):731–744.
  • ••The phenotype of the FXR-deficient mice.
  • KOK T, HULZEBOS CV, WOLTERS H et al.: Enterohepatic circulation of bile salts in farnesoid X receptor-deficient mice: efficient intestinal bile salt absorption in the absence of ileal bile acid-binding protein. Biol. Chem. (2003) 278(43):41930–41937.
  • ••The phenotype of the FXR-deficient mice.
  • CHIANG JY, KIMMEL R, C, STROUP D: Farnesoid receptor responds to bile acids and represses cholesterol 7a-hydroxylase gene (CYP7A1) transcription. I Biol. Chem. (2000) 275(15):10918–10924.
  • GOODWIN B, JONES SA, PRICE RR et al.: A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis. Ma Cell (2000) 6(3):517–526.
  • ••Description of the FXR-mediated negativefeedback on bile synthesis via SHP.
  • LU TT, MAKISHIMA M, REPA JJ et al: Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors. MM. Cell (2000) 6(3):507–515.
  • ••Description of the FXR-mediated negativefeedback on bile synthesis via SHP.
  • MIYAKE JH, WANG SL, DAVIS RA: Bile acid induction of cytokine expression by macrophages correlates with repression of hepatic cholesterol 7a-hydroxylase. Biol. Chem. (2000) 275(29):21805–21808.
  • HOLT JA, LUO G, BILLIN AN et al: Definition of a novel growth factor-dependent signal cascade for the suppression of bile acid biosynthesis. Genes Dev. (2003) 17(13):1581–1591.
  • YU C, WANG F, KAN M et al.: Elevated cholesterol metabolism and bile acid synthesis in mice lacking membrane tyrosine kinase receptor FGFR4. J. Biol. Chem. (2000) 275(20):15482–15489.
  • EINARSSON K, AKERLUND JE, REIHNER E, BJORKHEM I: 12 a-hydroxylase activity in human liver and its relation to cholesterol 7 a-hydroxylase activity.' Lipid Res. (1992) 33(11):1591–1595.
  • ZHANG M, CHIANG JY: Transcriptional regulation of the human sterol 12a-hydroxylase gene (CYP8B1). Roles of hepatocyte nuclear factor 4a in mediating bile acid repression. Biol. Chem. (2001) 276(45):41690–41699.
  • SCHERSTEN T, BJORNTORP P, EKDAHL PH, BJORKERUD S: The synthesis of taurocholic and glycocholic acids by preparations of human liver. II. An analysis of the stimulating effect of the L fraction. Biochim. Biophys. Acta (1967) 141(1):155–163.
  • CZUBA B, VESSEY DA: Purification and characterization of cholyl-CoA: taurine N-acetyltransferase from the liver of domestic fowl (Gallus gallus). Biochem. (1981) 195(1):263–266.
  • PIRCHER PC, KITTO JL, ML et al.: Farnesoid X receptor regulates bile acid-amino acid conjugation. J. Biol. Chem. (2003) 278(30):27703–27711.
  • HAGENBUCH B, STIEGER B, FOGUET M, LUBBERT H, MEIER PJ: Functional expression cloning and characterization of the hepatocyte Na+/bile acid cotransport system. Proc. Natl. Acad. Sci. USA (1991) 88(23):10629–10633.
  • HAGENBUCH B, MEIER PJ: Molecular cloning, chromosomal localization, and functional characterization of a human liver Na±/bile acid cotransporter. Clin. Invest. (1994) 93(3):1326–1331.
  • CATTORI V, ECKHARDT U, B: Molecular cloning and functional characterization of two alternatively spliced Ntcp isoforms from mouse liven. Biochim. Biophys. Acta (1999) 1445(1):154–159.
  • STIEGER B, HAGENBUCH B, LANDMANN L et al.: In situ localization of the hepatocytic Nehaurocholate cotransporting polypeptide in rat liver. Gastroenterology (1994) 107(6):1781–1787.
  • ANANTHANARAYANAN M, NG OC, BOYER JL, SUCHY FJ: Characterization of cloned rat liver Na() -bile acid cotransporter using peptide and fusion protein antibodies. Am. Physiol. (1994) 267(4 Pt 1):G637–643.
  • DENSON LA, STURM E, ECHEVARRIA W et al.: The orphan nuclear receptor, shp, mediates bile acid-induced inhibition of the rat bile acid transporter, Ntcp. Gastroenterology (2001) 121(1):140–147.
  • ABET, KAKYO M, TOKUI T et al.: Identification of a novel gene family encoding human liver-specific organic anion transporter LST-1. .1. Biol. Chem. (1999) 274(24):17159–17163.
  • HSIANG B, ZHU Y, WANG Z et al.: A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters. .1 Biol. Chem. (1999) 274(52):37161–37168.
  • KONIG J, CUT Y, NIES AT, KEPPLER D: A novel human organic anion transporting polypeptide localized to the basolateral hepatocyte membrane. Am. Physiol. Gastrointest. Liver Physiol. (2000) 278(1):G156–164.
  • FICKERT P, ZOLLNER G, FUCHSBICHLER A et al.: Effects of ursodeoxycholic and cholic acid feeding on hepatocellular transporter expression in mouse liver. Gastroenterology (2001) 121(1):170–183.
  • AGELLON LB, TORCHIA EC: transport of bile acids. Biochirn. Biophys. Acta (2000) 1486(1):198–209.
  • ADACHI Y, KAMISAKO T, T: The effects of temporary occlusion of the superior mesenteric vein or splenic vein on biliary bilirubin and bile acid excretion in rats. I Lab. Clio. Med. (1991) 118(3):261–268.
  • MULLER M, ISHIKAWA T, BERGER U et al.: ATP-dependent transport of taurocholate across the hepatocyte canalicular membrane mediated by a 110-kDa glycoprotein binding ATP and bile salt.jBioI. Chem. (1991) 266(28):18920–18926.
  • NISHIDA T, GATMAITAN Z, CHE M, ARIAS IM: Rat liver canalicular membrane vesicles contain an ATP-dependent bile acid system. Proc. Nati Acad. Sd. USA (1991) 88(15):6590–6594.
  • GERLOFF T, STIEGER B, HAGENBUCH B et al.: The sister of P-glycoprotein represents the canalicular bile salt export pump of mammalian liver. J. Biol. Chem. (1998) 273(16):10046–10050.
  • GREEN PM, HODA F, WARD KL: Molecular cloning and characterization of the murine bile salt export pump. Gene (2000) 241(1):117–123.
  • JANSEN PL, STRAUTNIEKS SS, JACQUEMIN E et al.: Hepatocanalicular bile salt export pump deficiency in patients with progressive familial intrahepatic cholestasis. Gastroenterology (1999) 117(6):1370–1379.
  • WANG R, SALEM M, YOUSEF IM et al.: Targeted inactivation of sister of P-glycoprotein gene (spgp) in mice results in nonprogressive but persistent intrahepatic cholestasis. Proc. Nati Acad. Sci. USA (2001) 98(4):2011–2016.
  • ANANTHANARAYANAN M, BALASUBRAMANIAN N, MAKISHIMA M, MANGELSDORF DJ, SUCHY FJ: Human bile salt export pump promoter is transactivated by the farnesoid receptor/bile acid receptor. Biol. Chem. (2001) 276(31):28857–28865.
  • PLASS JR, MOL O, HEEGSMA J et al.: Farnesoid X receptor and bile salts are involved in transcriptional regulation of the gene encoding the human bile salt export pump. Hepatology (2002) 35(3):589–596.
  • LAZARIDIS KN, PHAM L, TIETZ P et al.: Rat cholangiocytes absorb bile acids at their apical domain via the ileal sodium-dependent bile acid transporter. J. Chu. Invest. (1997) 100(11):2714–2721.
  • LAZARIDIS KN, TIETZ P, WU T et al.: Alternative splicing of the rat sodium/bile acid transporter changes its cellular localization and transport properties. Proc. Nati Acad. Sri. USA (2000) 97(20):11092–11097.
  • KOOL M, VAN DER LINDEN M, DE HAAS M et al.: MRP3, an organic anion transporter able to transport anti-cancer drugs. Proc. Natl. Acad. Sci. USA (1999) 96(12):6914–6919.
  • SOROKA CJ, LEE JM, AZZAROLI F, BOYER JL: Cellular localization and up-regulation of multidrug resistance-associated protein 3 in hepatocytes and cholangiocytes during obstructive in rat liver. Hepatology (2001) 33(4):783–791.
  • WONG MH, OELKERS P, AL, DAWSON PA: Expression cloning and characterization of the hamster ileal sodium-dependent bile acid transporter. j. Biol. Chem. (1994) 269(2):1340–1347.
  • WONG MH, OELKERS P, DAWSON PA: Identification of a mutation in the ileal sodium-dependent bile acid transporter gene that abolishes transport activity. J. Biol. Chem. (1995) 270(45):27228–27234.
  • SHNEIDER BL, DAWSON PA, CHRISTIE DM et al.: Cloning and molecular characterization of the ontogeny of a rat ileal sodium-dependent bile acid transporter.j Clio. Invest. (1995) 95(2):745–754.
  • SAEKI T, MATOBA K, FURUKAWA H et al.: Characterization, cDNA cloning, and functional expression of mouse ileal sodium-dependent bile acid transporter.. (Tokyo) (1999) 125(4):846–851.
  • DAWSON PA, HAYWOOD J, CRADDOCK AL et al.: Targeted deletion of the ileal bile acid transporter eliminates enterohepatic cycling of bile acids in mice. J. Biol. Chem. (2003) 278(36):33920–33927.
  • CHEN F, MA L, DAWSON PA et al.: Liver receptor homologue-1 mediates species- and cell line-specific bile acid-dependent negative feedback regulation of the apical sodium-dependent bile acid transporter. J. Biol. Chem. (2003) 278(22):19909–19916.
  • KRAMER W, CORSIERO D, M et al.: Intestinal absorption of bile acids: paradoxical behaviour of the 14 kDa ileal lipid-binding protein in differential photoaffinity labelling. Biochern. (1998) 333 (Pt 2):335–341.
  • INOKUCHI A, HINOSHITA E, IWAMOTO Y et al.: Enhanced expression of the human multidrug resistance protein 3 by bile salt in human enterocytes. A transcriptional control of a plausible bile acid transporter. j. Biol. Chem. (2001) 276(50):46822–46829.
  • BARNES S, BUCHINA ES, KING RJ, McBURNETT T, TAYLOR KB: Bile acid sulfotransferase I from rat liver sulfates bile acids and 3-hydroxy steroids: purification, N-terminal amino acid sequence, and kinetic properties. Lipid Res. (1989) 30(4):529–540.
  • SONG CS, ECHCHGADDA I, BAEK BS et al.: Dehydroepiandrosterone sulfotransferase gene induction by bile acid activated farnesoid x receptor. Biol. Chem. (2001) 276(45):42549–42556.
  • PILLOT T, OUZZINE M, FOURNEL-GIGLEUX S et al.: Glucuronidation of hyodeoxycholic acid in human liver. Evidence for a selective role of UDP-glucuronosyltransferase 2B4. J. Biol. Chem. (1993) 268(34):25636–25642.
  • MONAGHAN G, BURCHELL B, BOXER M: Structure of the human UGT2B4 gene encoding a bile acid UDP-glucuronosyltransferase. Mamm. Genome (1997) 8(9):692–694.
  • MILLER NE, LA VILLE A, CROOK D: Direct evidence that reverse cholesterol transport is mediated by high-density lipoprotein in rabbit. Nature (London) (1985) 314(6006):109–111.
  • BARD JM, PARRA HJ,-BLAZY P, FRUCHART JC: Effect of pravastatin, an HMG CoA reductase inhibitor, and cholestyramine, a bile acid sequestrant, on lipoprotein particles defined by their apolipoprotein composition. Metabolism (1990) 39(3):269–273.
  • HAGEN E, ISTAD H, OSE L et al.: Fluvastatin efficacy and tolerability in comparison and in combination with cholestyramine. Eur: Clin. Pharmacol (1994) 46(5):445–449.
  • LEISS O, VON BERGMANN K: Different effects of chenodeoxycholic acid and ursodeoxycholic acid on serum lipoprotein concentrations in patients with radiolucent gallstones. Scand. Gastroenterol (1982) 17(5):587–592.
  • KURIYAMA M, TOKIMURA Y, FUJIYAMA J, UTATSU Y, OSAME M: Treatment of cerebrotendinous xanthomatosis: effects of chenodeoxycholic acid, pravastatin, and combined use. Sci (1994) 125(1):22–28.
  • URIZAR NL, DOWHAN DH, MOORE DD: The farnesoid X-activated receptor mediates bile acid activation of phospholipid transfer protein gene expression. Biol. Chem. (2000) 275(50):39313–39317.
  • MOLGAARD J, VON SCHENCK H, OLSSON AG: Comparative effects of simvastatin and cholestyramine in treatment of patients with hypercholesterolaemia.. Pharmacol (1989) 36(5):455–460.
  • BUCHWALD H, VARCO RL, MATTS JP et al.: Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. Report of the Program on the Surgical Control of the Hyperlipidemias (POSCH). N Engl. Med. (1990) 323(14):946–955.
  • REPA JJ, LUND EG, HORTON JD et al: Disruption of the sterol 27-hydroxylase gene in mice results in hepatomegaly and hypertriglyceridemia. Reversal by cholic acid feeding. Biol. Chem. (2000) 275(50):39685–39692.
  • CLAUDEL T, INOUE Y, BARBIER 0 et al.: Farnesoid X receptor agonists suppress hepatic apolipoprotein CIII expression. Gastroenterology (2003) 125(2):544–555.
  • PENNACCHIO LA, OLIVIER M, HUBACEK JA et al.: An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing. Science (2001) 294(5540):169–173.
  • PRIEUR X, COSTE H, RODRIGUEZ JC: The human apolipoprotein AV gene is regulated by perwdsome proliferator-activated receptor-a and contains a novel farnesoid X-activated receptor response element. J. Biol. Chem. (2003) 278(28):25468–25480.
  • WILLIAMS KJ, FLESS GM, PETRIE KA et al.: Mechanisms by which lipoprotein lipase alters cellular metabolism of lipoprotein(a), low density lipoprotein, and nascent lipoproteins. Roles for low density lipoprotein receptors and heparan sulfate proteoglycans. J. Biol. Chem. (1992) 267(19):13284–13292.
  • ANISFELD AM, KAST-WOELBERN HR, MEYER ME et al: Syndecan-1 expression is regulated in an isoform specific manner by the farnesoid-X receptor. Biol. Chem. (2003) 26:26.
  • WILLSON TM, BROWN PJ, STERNBACH DD, HENKE BR: The PPARs: from orphan receptors to drug discovery. J. Med. Chem. (2000) 43(4):527–550.
  • STAELS B, DALLONGEVILLE J, AUWERX J et al.: Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation (1998) 98(19)2088–2093.
  • PATEL DD, KNIGHT BL, SOUTAR AK, GIBBONS GE WADE DP: The effect of peroxisome-proliferator-activated receptor-a on the activity of the cholesterol 7 a-hydroxylase gene. Biochem. .1. (2000) 351 (Pt 3):747–753.
  • POST SM, DUEZ H, GERVOIS PP et al.: Fibrates suppress bile acid synthesis via perwdsome proliferator- activated receptor-a-mediated downregulation of cholesterol 7a- hydroxylase and sterol 27-hydroxylase expression. Arteriosclec Thromb. Vasc. Biol. (2001) 21(11):1840–1845.
  • PINEDA TORRA I, CLAUDEL T, DUVAL C et al.: Bile acids induce the expression of the human peroxisome proliferator- activated receptor-a gene via activation of the farnesoid X receptor. Ma Endocrinol (2003) 17(2):259–272.
  • ZHANG Y, CASTELLANI LW, SINAL CJ, GONZALEZ FJ, EDWARDS PA: Peroxisome proliferator-activated receptor-y coactivator la (PGC-1a) regulates triglyceride metabolism by activation of the nuclear receptor FXR. Genes Dev. (2004) 18(2):157–169.
  • JANSEN PL, MULLER M, STURM E: Genes and cholestasis. Hepatology (2001) 34(6):1067–1074.
  • SHNEIDER BL, FOX VL, KB et al.: Hepatic basolateral sodium-dependent-bile acid transporter expression in two unusual cases of hypercholanemia and in extrahepatic biliary atresia. Hepatology (1997) 25(5):1176–1183.
  • ZOLLNER G, FICKERT P, ZENZ R et al: Hepatobiliary transporter expression in percutaneous liver biopsies of patients with cholestatic liver diseases. Hepatology (2001) 33(3):633–646.
  • RIUS M, NIES AT, HUMMEL-EISENBEISS J, JEDLITSCHKY G, KEPPLER D: Cotransport of reduced glutathione with bile salts by MRP4 (ABCC4) localized to the basolateral hepatocyte membrane. Hepatology (2003) 38(2):374–384.
  • ZOLLNER G, FICKERT P, A et al.: Role of nuclear bile acid receptor, FXR, in adaptive ABC transporter regulation by chofic and ursodeoxycholic acid in mouse liver, kidney and intestine. J. Hepatol (2003) 39(4)480–488.
  • PAUMGARTNER G, BEUERS U: Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited. Hepatology (2002) 36(3):525–531.. LEW JL, ZHAO A, YU J et al.: The farnesoid X receptor controls gene expression in a ligand- and promoter-selective fashion. Biol. Chem. (2004) 279(10):8856–8861.
  • TRAUNER M, METER PJ, BOYER JL: Molecular pathogenesis of cholestasis. N Engl. I Med. (1998) 339(17):1217–1227.
  • PUNTIS MC, JIANG WG: Plasma cytokine levels and monocyte activation in patients with obstructive jaundice. Gastroenterol Hepatol (1996) 11(1):7–13.
  • BEMELMANS MH, GOUMA DJ, GREVE JW, BUURMAN WA: Cytokines tumor necrosis factor and interleukin-6 in experimental biliary obstruction in mice. Hepatology (1992) 15(6):1132–1136.
  • PLEBANI M, PANOZZO MP, BASSO D et al.: Cytokines and the progression of liver damage in experimental bile duct ligation. Clin. Exp. Pharmacol Physiol (1999) 26(4):358–363.
  • LIU Y, BINZ J, NUMERICK MJ et aL: Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intra- and extrahepatic cholestasis. Clin. Invest. (2003)
  • WAGNER M, FICKERT P, ZOLLNER G et al.: Role of farnesoid X receptor in determining hepatic ABC transporter expression and liver injury in bile duct-ligated mice. Gastroenterology (2003) 125(3):825–838.
  • CHISHOLM JW, DOLPHIN PJ: Abnormal lipoproteins in the ANIT-treated rat: a transient and reversible animal model of intrahepatic cholestasis. J Lipid Res. (1996) 37(5):1086–1098.
  • ORSLER DJ, AHMED-CHOUDHURY J, CHIPMAN JK, HAMMOND T, COLEMAN R: ANIT-induced disruption of biliary function in rat hepatocyte couplets. Toxica Sci. (1999) 47(2):203–210.
  • GOULIS J, LEANDRO G, BURROUGHS AK: Randomised controlled trials of ursodeoxycholic-acid therapy for primary biliary cirrhosis: a meta-analysis. Lancet (1999) 354(9184):1053–1060.
  • CLAYTON PT, MILLS KA, AW, BARABINO A, MARAZZI MG: M-3-oxosteroid 5 P-reductase deficiency: failure of ursodeoxycholic acid treatment and response to chenodeoxycholic acid plus cholic acid. Gut (1996) 38(4):623–628.
  • ICHIMIYA H, EGESTAD B, NAZER H et al.: Bile acids and bile alcohols in a child with hepatic 3 3-hydroxy-8 5-C27-steroid dehydrogenase deficiency: effects of chenodeoxycholic acid treatment. Lipid Res. (1991) 32(5):829–841.
  • ICHIMIYA H, NAZER H, GUNASEKARAN T, CLAYTON P, SJOVALL J: Treatment of chronic liver disease caused by 3 3-hydroxy-8 5-C27-steroid dehydrogenase deficiency with chenodeoxycholic acid. Arch. Dis. Child. (1990) 65(10):1121–1124.
  • GULDUTUNA S, LEUSCHNER M, WUNDERLICH N et al.: Cholic acid and ursodeoxycholic acid therapy in primary biliary cirrhosis. Changes in bile acid patterns and their correlation with liver function. Ear: I Clin. Pharmacol (1993) 45(3):221–225.
  • MILLER GJ, MILLER NE: Plasma-high-density-lipoprotein concentration and development of ischaemic heart-disease. Lancet (1975) 1(7897):16–19.
  • GORDON T, CASTELLI WP, HJORTLAND MC, KANNEL WB, DAWBER TR: High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am. Med. (1977) 62(5):707–714.
  • RUBINS HB, ROBINS SJ, COLLINS D et al.: Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl. I Med. (1999) 341(6):410–418.
  • AUSTIN MA: Plasma triglyceride and coronary heart disease. Arteriosclec Thromb. (1991) 11(1):2–14.
  • ASSMANN G, SCHULTE H, FUNKE H, VON ECKARDSTEIN A: The emergence of triglycerides as a significant independent risk factor in coronary artery disease. Ear: Heart (1998) 19(Suppl. M):M8–M14.
  • HODIS HN: Triglyceride-rich lipoprotein remnant particles and risk of atherosclerosis. Circulation (1999) 99(22):2852–2854.
  • SACKS FM, ALAUPOVIC P, MOYE LA et al.: VLDL, apolipoproteins B, CIII, and E, and risk of recurrent coronary events in the Cholesterol and Recurrent Events (CARE) trial. Circulation (2000) 102(16):1886–1892.
  • DEV S: Ethnotherapeutics and modern drug development the potential of Ayurveda. Can: Sci. (1997) 73:909–928.
  • SATYAVATI GV, DWARAKANATH C, TRIPATHI SN: Experimental studies on the hypocholesterolemic effect of Commiphora mukul. Engl. (Guggul). Indian Med. Res. (1969) 57(10):1950–1962.
  • NITYANAND S, KAPOOR NK: Cholesterol lowering activity of the various fractions of guggul,. Indian I Exp. Biol. (1973) 11:395–398.
  • URIZAR NL, LIVERMAN AB, DT et al: A natural product that lowers cholesterol as an antagonist ligand for FXR. Science (2002) 296(5573):1703–1706.
  • CUI J, HUANG L, ZHAO A et al.: Guggulsterone is a farnesoid X receptor antagonist in coactivator association assays but acts to enhance transcription of bile salt export pump. I Biol. Chem. (2003) 278(12):10214–10220.
  • SZAPARY PO, WOLFE ML, LT et al: Guggulipid for the treatment of hypercholesterolemia: a randomized controlled trial. JAMA (2003) 290(6):765–772.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.