Effect of Water Extract of Fructus Gardenia on Sulfated Bile Acids in Rats with Estrogen-Induced Cholestasis and Its Mechanism
ZHANG Guo-qiang1, WEI Yu-hui1, WEN Yuan-jie1,2, RAO Zhi1, SUN Wen-hui1,3, WANG Qian1,3, XIAN Ke-yao1,3, WU Xin′an1*
1. Department of Pharmacy, The First Hospital of Lanzhou University, Lanzhou 730000, China; 2. College of Pharmaceutical Science, Lanzhou University, Lanzhou 730000, China; 3. The First Clinical Medical College of Lanzhou University, Lanzhou 730000, China
Abstract:OBJECTIVE To investigate the effects of water extract of Fructus Gardenia on the sulfated bile acids in liver, blood, feces and urine of rats with estrogen-induced cholestasis and its possible mechanism. METHODS Wistar rats were randomly divided into control group, model group and Gardenia group. Intrahepatic cholestasis model was established by subcutaneous injection of ethinylestradiol (5 mg·kg-1) for 5 d, and the water extract of Gardenia (120 mg·kg-1, twice a day) was orally administered for 7 d. The levels of sulfated bile acids in urine, feces, blood and liver tissues and the expression of Sult2a1, Mrp2 and Mrp4 in liver and kidney were determined, respectively. RESULTS Gardenia water extract improved the hepatic lesions, increased the levels of liver, blood, urine and fecal sulfated bile acids (P<0.05) and increased the expression of Sult2a1, Mrp2 and Mrp4 in liver and the expression of Sult2a1 and Mrp4 in kidney in EE-treated rats (P<0.05). CONCLUSION Gardenia water extract can accelerate the sulfation transformation and excretion of bile acids in liver and kidney, improve estrogen-induced intrahepatic cholestasis in rats, which may be related to upregulation of the expression of Sult2a1, Mrp2 and Mrp4 in liver and kidney.
张国强, 魏玉辉, 文苑洁, 饶志, 孙文惠, 王茜, 先柯瑶, 武新安. 栀子水提物对雌激素诱导的胆汁淤积大鼠中硫酸化胆酸盐的影响及机制研究[J]. 中国药学杂志, 2020, 55(20): 1680-1685.
ZHANG Guo-qiang, WEI Yu-hui, WEN Yuan-jie, RAO Zhi, SUN Wen-hui, WANG Qian, XIAN Ke-yao, WU Xin′an. Effect of Water Extract of Fructus Gardenia on Sulfated Bile Acids in Rats with Estrogen-Induced Cholestasis and Its Mechanism. Chinese Pharmaceutical Journal, 2020, 55(20): 1680-1685.
TANG L, YU X L, ZHU Z F, et al. Effect of phospholipid complex on the degradation of geniposide by rat intestinal flora in vitro . Chin Pharm J (中国药学杂志), 2018,53(24):2090-2095.
[2]
YAO Y, GUO H, MA X, et al. The protective effect of Zhizichi Decoction on the apoptosis of PC12 cells induced by glutamic acid . Chin Pharm J (中国药学杂志), 2018, 53(12):982-987.
[3]
WANG L, WU G, WU F, et al. Geniposide attenuates ANIT-induced cholestasis through regulation of transporters and enzymes involved in bile acids homeostasis in rats . J Ethnopharmacol, 2017, 196:178-185.
[4]
CHEN P, CHEN Y, WANG Y, et al. Comparative evaluation of hepatoprotective activities of geniposide, crocins and crocetin by CCl4-induced liver injury in mice . Biomol Ther (Seoul), 2016, 24(2):156-162.
[5]
ASHBY K, NAVARRO ALMARIO E E, TONG W, et al. Review article: therapeutic bile acids and the risks for hepatotoxicity . Aliment Pharmacol Ther, 2018, 47(12):1623-1638.
[6]
YANG T, KHAN G J, WU Z, et al. Bile acid homeostasis paradigm and its connotation with cholestatic liver diseases . Drug Discov Today, 2019, 24(1):112-128.
[7]
ALNOUTI Y. Bile acid sulfation: a pathway of bile acid elimination and detoxification . Toxicol Sci, 2009, 108(2):225-246.
[8]
ASSEM M, SCHUETZ E G, LEGGAS M, et al. Interactions between hepatic Mrp4 and Sult2a as revealed by the constitutive androstane receptor and Mrp4 knockout mice . J Biol Chem, 2004, 279(21):22250-22257.
[9]
KUROGI K, KRASOWSKI M D, INJETI E, et al. A comparative study of the sulfation of bile acids and a bile alcohol by the Zebra danio (Danio rerio) and human cytosolic sulfotransferases (SULTs) . J Steroid Biochem Mol Biol, 2011, 127(3-5):307-314.
[10]
RODRIGUEZ-GARAY E A. Cholestasis: human disease and experimental animal models . Ann Hepatol, 2003, 2(4):150-158.
[11]
ZHAO Y S. Preliminary Study on the Molecular Mechanism of Gardenia Jasminoides (Zhi-zi) Aqueous Extract for the Treatmentof Jaundice and Cholestasis Via Bilirubin and Bile Acids Relevant Transporter-enzyme Systems in Rats . Lanzhou: Lanzhou University, 2017.
[12]
SONG P, ZHANG Y, KLAASSEN C D. Dose-response of five bile acids on serum and liver bile acid concentrations and hepatotoxicty in mice . Toxicol Sci, 2011, 123(2):359-367.
[13]
DAWSON P A. Role of the intestinal bile acid transporters in bile acid and drug disposition . Hand Exp Pharmacol, 2011, 201:169-203.
[14]
HUANG J, BATHENA S P, TONG J, et al. Kinetic analysis of bile acid sulfation by stably expressed human sulfotransferase 2A1 (SULT2A1) . Xenobiotica, 2010, 40(3):184-94.