Adil M, Kandhare AD, Ghosh P, Venkata S,
Raygude KS, Bodhankar SL. 2016.
Ameliorative effect of naringin in
acetaminophen-induced hepatic and renal
toxicity in laboratory rats: role of FXR and
KIM-1. Ren Fail, 38: 1007-1020.
Aguilar-Olivos NE, Carrillo-Córdova D, OriaHernández J, Sánchez-Valle V, PoncianoRodríguez G, Ramírez-Jaramillo M,
Chablé-Montero F, Chávez-Tapia NC,
Uribe M, Méndez-Sánchez N. 2015. The
nuclear receptor FXR, but not LXR, upregulates bile acid transporter expression in
non-alcoholic fatty liver disease. Ann
Hepatol, 14: 487-493.
Akhondzadeh S, Tahmacebi‐Pour N, Noorbala
AA, Amini H, Fallah‐Pour H, Jamshidi AH,
Khani M. 2005. Crocus sativus L. in the
treatment of mild to moderate depression: a
double‐blind, randomized and placebo‐
Khalili et al.
AJP, Vol. 11, No. 4, Jul-Aug 2021 378
controlled trial. Phytother Res 19:148-151.
Bijak M. 2017. Silybin, a Major Bioactive
Component of Milk Thistle (Silybum
marianum L. Gaernt.)-Chemistry,
Bioavailability, and Metabolism. Molecules
22: 1942.
Cavin C, Delannoy M, Malnoe A, Debefve E,
Touché A, Courtois D, Schilter B. 2005.
Inhibition of the expression and activity of
cyclooxygenase-2 by chicory extract.
Biochem. Biophys Res Commun, 327: 742-
749.
Conforti F, Ioele G, Statti GA, Marrelli M,
Ragno G, Menichini F. 2008.
Antiproliferative activity against human
tumor cell lines and toxicity test on
Mediterranean dietary plants. Food Chem
Toxicol, 46: 3325-3332.
de Avelar CR, Pereira EM, de Farias Costa PR,
de Jesus RP, de Oliveira LPM. 2017. Effect
of silymarin on biochemical indicators in
patients with liver disease: Systematic
review with meta-analysis. World J
Gastroenterol, 23: 5004-5017.
Del Campo JA, Gallego P, Grande L. 2018.
Role of inflammatory response in liver
diseases: Therapeutic strategies. World J
Hepatol, 10: 1-7.
Gupta SC, Tyagi AK, Deshmukh-Taskar P,
Hinojosa M, Prasad S, Aggarwal BB. 2014.
Downregulation of tumor necrosis factor
and other proinflammatory biomarkers by
polyphenols. Arch Biochem Biophys, 559:
91-99.
Hylemon PB, Takabe K, Dozmorov M,
Nagahashi M, Zhou H. 2017. Bile acids as
global regulators of hepatic nutrient
metabolism. Liver Research, 1: 10-16.
Jacinto S, Fang S. 2014. Essential roles of bile
acid receptors FXR and TGR5 as metabolic
regulators. Animal Cells and Systems, 18:
359-364.
Jamshidzadeh A, Khoshnood MJ, Dehghani Z,
Niknahad H. 2010. Hepatoprotective
Activity of Cichorium intybus L. Leaves
Extract Against Carbon Tetrachloride
Induced Toxicity. IJPR, 5: 41-46.
Jassim AM. 2013. Protective Effect of
Petroselinum crispum (parsley) extract on
histopathological changes in liver, kidney
and pancreas induced by Sodium ValproateIn male Rats. Kufa J Vet Sci, 4: 20-27.
Jiang Q, Peng J, Liu SN, Shen ZF. 2015.
Farnesoid X receptor regulates glucose and
lipid metabolisms. Yao Xue Xue Bao 50:
245-251.
Kailash C, Swatantra Kumar J. 2016.
Therapeutic potential of cichorium intybus
in lifestyle disorders: a review.Asian
J Pharm Clin Res, 9: 20-25.
Kong B, Zhu Y, Li G, Williams JA, Buckley K,
Tawfik O, Luyendyk JP, Guo GL. 2016.
Mice with hepatocyte-specific FXR
deficiency are resistant to spontaneous but
susceptible to cholic acid-induced
hepatocarcinogenesis. Am J Physiol
Gastrointest Liver Physiol, 310: G295-
G302.
Lee FY, de Aguiar Vallim TQ, Chong HK,
Zhang Y, Liu Y, Jones SA, Osborne TF,
Edwards PA. 2010. Activation of the
farnesoid X receptor provides protection
against acetaminophen-induced hepatic
toxicity. Mol Endocrinol, 24: 1626-1636.
Li G-Y, Gao H-Y, Huang J, Lu J, Gu J-K, Wang
J-H. 2014. Hepatoprotective effect of
Cichorium intybus L., a traditional Uighur
medicine, against carbon tetrachlorideinduced hepatic fibrosis in rats. World J
Gastroenterol, 20: 4753-4760.
Li G, Guo L. 2015. Farnesoid X receptor, the
bile acid sensing nuclear receptor, in liver
regeneration. Acta Pharm Sin B 5:93-98.
Li T, Chiang JYL. 2013. Nuclear receptors in
bile acid metabolism. Drug Metab Rev, 45:
145-155.
Massafra V, Ijssennagger N, Plantinga M,
Milona A, Ramos Pittol JM, Boes M, van
Mil SWC. 2016. Splenic dendritic cell
involvement in FXR-mediated amelioration
of DSS colitis. BBA Mol Basis Dis, 1862:
166-173.
Mazraati P, Minaiyan M. 2018.
Hepatoprotective Effect of Metadoxine on
Acetaminophen-induced Liver Toxicity in
Mice. ABR, 7: 67-67.
Pathak P, Liu H, Boehme S, Xie C, Krausz KW,
Gonzalez F, Chiang JYL. 2017. Farnesoid X
receptor induces Takeda G-protein receptor
5 cross-talk to regulate bile acid synthesis
and hepatic metabolism. J Biol Chem, 292:
11055-11069.
Sadat Sharifi, Bakhshaei. 2017.
Pharmacological effect of seven medicinal
plants as a traditional preparation. IIOABJ,
8: 8-12.
Safari F, Bayat G, Shekarforoush S,
Hekmatimoghaddam S, Anvari Z,
Moghadam MF, Sohrab Hajizadeh. 2014.
Expressional profile of cardiac uncoupling
Effect of chicory and silymarin on hepatic FXR expression
AJP, Vol. 11, No. 4, Jul-Aug 2021 379
protein-2 following myocardial ischemia
reperfusion in losartan- and ramiprilattreated rats. Journal of the reninangiotensin-aldosterone system. JRAAS,
15: 209-217.
Schmidt BM, Ilic N, Poulev A, Raskin I. 2007.
Toxicological evaluation of a chicory root
extract. Food Chem Toxicol, 45:1131-1139.
Shaik FB, Prasad DV, Narala VR. 2015. Role
of farnesoid X receptor in inflammation, and
resolution. Inflamm Res 64: 9-20.
Soliman HA, El-Desouky MA, Hozayen WG,
Ahmed RR, Khaliefa AK. 2016.
Hepatoprotective effects of parsley, basil,
and chicory aqueous extracts against
dexamethasone-induced in experimental
rats. JCMR, 5: 65-71.
Stevenson DE, Hurst RD. 2007. Polyphenolic
phytochemicals--just antioxidants or much
more? Cell Mol Life Sci, 64: 2900-2916.
Stiuso P, Scognamiglio I, Murolo M, Ferranti
P, De Simone C, Rizzo MR, Tuccillo C,
Caraglia M, Loguercio C, Federico A. 2014.
Serum oxidative stress markers and
lipidomic profile to detect NASH patients
responsive to an antioxidant treatment: a
pilot study. Oxid Med Cell Longev, 2014:
169216.
Su H, Ma C, Liu J, Li N, Gao M, Huang A,
Wang X, Huang W, Huang X. 2012.
Downregulation of nuclear receptor FXR is
associated with multiple malignant
clinicopathological characteristics in human
hepatocellular carcinoma. Am J Physiol
Gastrointest Liver Physiol, 303: G1245-
1253.
Surai PF. 2015. Silymarin as a Natural
Antioxidant: An Overview of the Current
Evidence and Perspectives. Antioxidants
(Basel), 4: 204-247.
Taoka H, Yokoyama Y, Morimoto K, Kitamura
N, Tanigaki T, Takashina Y, Tsubota K,
Watanabe M. 2016. Role of bile acids in the
regulation of the metabolic pathways. World
J Diabetes, 7: 260-270.
Tsaroucha AK, Valsami G, Kostomitsopoulos
N, Lambropoulou M, Anagnostopoulos C,
Christodoulou E, Falidas E, Betsou A,
Pitiakoudis M, Simopoulos CE. 2018.
Silibinin Effect on Fas/FasL, HMGB1, and
CD45 Expressions in a Rat Model Subjected
to Liver Ischemia-Reperfusion Injury. J
Invest Surg, 31: 1-12.
van Golen RF, Olthof PB, Lionarons DA,
Reiniers MJ, Alles LK, Uz Z, de Haan L,
Ergin B, de Waart DR, Maas A,
JoanneVerheij, Peter L. Jansen, StevenW.
Olde Damink, FrankG. Schaap, Thomas M.
vanGulik & Michal Heger. 2018. FXR
agonist obeticholic acid induces liver
growth but exacerbates biliary injury in rats
with obstructive cholestasis. Sci rep, 8:
16529.
Verbeke L, Farre R, Trebicka J, Komuta M,
Roskams T, Klein S, Elst IV, Windmolders
P, Vanuytsel T, Nevens F, Laleman W.
2014. Obeticholic acid, a farnesoid X
receptor agonist, improves portal
hypertension by two distinct pathways in
cirrhotic rats. Hepatology, 59: 2286-2298.
Verbeke L, Mannaerts I, Schierwagen R,
Govaere O, Klein S, Vander Elst I,
Windmolders P, Farre R, Wenes M,
Mazzone M, Nevens F, van Grunsven LA,
Trebicka J, Laleman W. 2016. FXR agonist
obeticholic acid reduces hepatic
inflammation and fibrosis in a rat model of
toxic cirrhosis. Sci Rep, 6: 33453.
Zhang S, Wang J, Liu Q, Harnish DC. 2009.
Farnesoid X receptor agonist WAY-362450
attenuates liver inflammation and fibrosis in
murine model of non-alcoholic
steatohepatitis. J Hepatol, 51: 380-388.