Beneficial effect of resveratrol on -naphthyl isothiocyanate-induced cholestasis via regulation of the FXR pathway

被引:30
作者
Ding, Lili [1 ,2 ,3 ]
Zhang, Binfeng [1 ,2 ,4 ]
Li, Jinmei [1 ,2 ,3 ]
Yang, Li [1 ,2 ,3 ]
Wang, Zhengtao [1 ,2 ,4 ]
机构
[1] Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, Shanghai Key Lab Compound Chinese Med, 1200 Cai Lun Rd, Shanghai 201203, Peoples R China
[2] Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, Minist Educ, Key Lab Standardizat Chinese Med, 1200 Cai Lun Rd, Shanghai 201203, Peoples R China
[3] Shanghai Univ Tradit Chinese Med, Ctr Chinese Med Therapy & Syst Biol, Shanghai 201203, Peoples R China
[4] Shanghai R&D Ctr Standardizat Tradit Chinese Med, Shanghai 201203, Peoples R China
基金
中国博士后科学基金;
关键词
resveratrol; farnesoid X receptor; cholestasis; -naphthylisothiocyanate; inflammation; ANIT-INDUCED HEPATOTOXITY; BILE-ACID HOMEOSTASIS; NUCLEAR RECEPTOR FXR; FARNESOID-X-RECEPTOR; ALPHA-NAPHTHYLISOTHIOCYANATE; INTRAHEPATIC CHOLESTASIS; MEDIATED REGULATION; EXPRESSION; TRANSPORTERS; MECHANISM;
D O I
10.3892/mmr.2017.8051
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Cholestasis is defined as a functional impairment of bile secretion which results in the accumulation of bile acids (BAs) and other toxic molecules in the blood and liver, however, there are very few effective therapies for cholestasis. The farnesoid X receptor (FXR), as a nuclear receptor for BAs, is important in the regulation of BA levels in enterohepatic circulation. It has previously been demonstrated that activation of the FXR pathway may be a useful strategy with which to treat cholestasis. Resveratrol, one of the important ingredients from grape skins and Chinese medicine Polygonum cuspidatum, resulted in FXR-activated effects in vitro and exhibited a protective effect against -naphthylisothiocyanate (ANIT)-induced cholestasis through FXR regulation in vivo. The underlying mechanisms of resveratrol against ANIT-induced cholestasis may be due to the regulation of BA homeostasis, improvement of liver injury and attenuation of the inflammatory response, which were regulated in a FXR-dependent manner and in turn contributed to overall cholestasis alleviation. Overall, resveratrol as a FXR agonist may act as a potential compound for the treatment of drug-induced cholestasis.
引用
收藏
页码:1863 / 1872
页数:10
相关论文
共 29 条
[1]   Geniposidic acid protected against ANIT-induced hepatotoxity and acute intrahepatic cholestasis, due to Fxr-mediated regulation of Bsep and Mrp2 [J].
Chen, Hao ;
Huang, Xiaotao ;
Min, Jianbin ;
Li, Weirong ;
Zhang, Rong ;
Zhao, Wei ;
Liu, Changhui ;
Yi, Lang ;
Mi, Suiqing ;
Wang, Ningsheng ;
Wang, Qi ;
Zhu, Chenchen .
JOURNAL OF ETHNOPHARMACOLOGY, 2016, 179 :197-207
[2]   Bile acid nuclear receptor FXR and digestive system diseases [J].
Ding, Lili ;
Yang, Li ;
Wang, Zhengtao ;
Huang, Wendong .
ACTA PHARMACEUTICA SINICA B, 2015, 5 (02) :135-144
[3]   Pathogenesis of Primary Sclerosing Cholangitis and Advances in Diagnosis and Management [J].
Eaton, John E. ;
Talwalkar, Jayant A. ;
Lazaridis, Konstantinos N. ;
Gores, Gregory J. ;
Lindor, Keith D. .
GASTROENTEROLOGY, 2013, 145 (03) :521-536
[4]   Differential effects of norUDCA and UDCA in obstructive cholestasis in mice [J].
Fickert, Peter ;
Pollheimer, Marion J. ;
Silbert, Dagmar ;
Moustafa, Tarek ;
Halilbasic, Emina ;
Krones, Elisabeth ;
Durchschein, Franziska ;
Thueringer, Andrea ;
Zollner, Gernot ;
Denk, Helmut ;
Trauner, Michael .
JOURNAL OF HEPATOLOGY, 2013, 58 (06) :1201-1208
[5]  
Flora K D, 1998, Clin Liver Dis, V2, P51, DOI 10.1016/S1089-3261(05)70363-9
[6]   A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis [J].
Goodwin, B ;
Jones, SA ;
Price, RR ;
Watson, MA ;
McKee, DD ;
Moore, LB ;
Galardi, C ;
Wilson, JG ;
Lewis, MC ;
Roth, ME ;
Maloney, PR ;
Willson, TM ;
Kliewer, SA .
MOLECULAR CELL, 2000, 6 (03) :517-526
[7]   BILE-ACIDS INHIBIT ENDOTOXIN-INDUCED RELEASE OF TUMOR NECROSIS FACTOR BY MONOCYTES - AN INVITRO STUDY [J].
GREVE, JW ;
GOUMA, DJ ;
BUURMAN, WA .
HEPATOLOGY, 1989, 10 (04) :454-458
[8]   Role of NF-κB in regulation of PXR-mediated gene expression -: A mechanism for the suppression of cytochrome P-450 3A4 by proinflammatory agents [J].
Gu, Xinsheng ;
Ke, Sui ;
Liu, Duan ;
Sheng, Tao ;
Thomas, Paul E. ;
Rabson, Arnold B. ;
Gallo, Michael A. ;
Xie, Wen ;
Tian, Yanan .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (26) :17882-17889
[9]   REVIEWS IN BASIC AND CLINICAL GASTROENTEROLOGY AND HEPATOLOGY [J].
Hirschfield, Gideon M. ;
Chapman, Roger W. ;
Karlsen, Tom H. ;
Lammert, Frank ;
Lazaridis, Konstantinos N. ;
Mason, Andrew L. .
GASTROENTEROLOGY, 2013, 144 (07) :1357-1374
[10]   Generation of multiple farnesoid-X-receptor isoforms through the use of alternative promoters [J].
Huber, RM ;
Murphy, K ;
Miao, B ;
Link, JR ;
Cunningham, MR ;
Rupar, MJ ;
Gunyuzlu, PL ;
Haws, TF ;
Kassam, A ;
Powell, F ;
Hollis, GF ;
Young, PR ;
Mukherjee, R ;
Burn, TC .
GENE, 2002, 290 (1-2) :35-43