Yinzhihuang attenuates ANIT-induced intrahepatic cholestasis in rats through upregulation of Mrp2 and Bsep expressions

Abstract

Background:The treatment of intrahepatic cholestasis has been limited, and development of an effective drug is needed. Clinical studies have shown that Yinzhihuang (YZH), a traditional Chinese decoction, enhances bilirubin clearance. The goal of this study was to determine the protective effect of YZH on experimental intrahepatic cholestasis in young rats and to explore its underlying molecular mechanisms. Methods: Intrahepatic cholestasis in rats was induced by α-naphthylisothiocyanate (ANIT) on days 1 and 8. The rats received YZH, ursodeoxycholic acid (UDCA), or vehicle for 9 d and were killed on either day 3 or day 10. Serum biomarkers, liver histology, and the distribution of protein and mRNA expression of Mrp2 and Bsep were analyzed. results: YZH treatment resulted in decreased levels of serum biomarkers except γ-glutamyl transpeptidase, attenuated liver histological injuries, increased protein expressions of Mrp2 and Bsep, and upregulated expressions of Mrp2 and Bsep mRNAs. The effects of YZH on serum biomarkers (aminotransferase, alanine aminotransferase, and direct bilirubin), liver histology, and Mrp2 mRNA expressions were significantly greater and earlier than those of UDCA. conclusion: Our results suggest that YZH has protective effect against ANIT-induced intrahepatic cholestasis in rats, through upregulation of Mrp2 and Bsep expressions.

Dioscin protects against ANIT–induced cholestasis via regulating Oatps, Mrp2 and Bsep expression in rats

“…4 and 6). Interestingly, the results were contradictory to ANIT-reduced Mrp2 and Bsep expression reported in a recent study (Ou et al, 2016) as well as unchanged Bsep, Mrp2 and SHP expression reported in a previous study on FXR agonist GW4064 (Liu et al, 2003). In addition, bile duct ligation or lipopolysaccharide (LPS) treatment resulted in an IL-1β-mediated retinoic acid receptor alpha (RARα)/retinoid X receptor alpha (RXRα) downregulation, which in turn decreased Mrp2 transcription in rats (Denson et al, 2002;Takikawa, 2002).…”

Protective effect of Echinochrome against intrahepatic cholestasis induced by alpha-naphthylisothiocyanate in rats

“…Alkaline phosphatase (ALP) is determined in the cells of the bile duct and is often employed to assess the reliability of the plasma membrane of the liver (Ou et al, 2016). The data recorded in the present study showed a significant increase of the serum ALP activity in cholestatic rats, which consonance with the findings of Lin et al (2012).…”

“…On the other hand, treatment with Ech causes a general decrease in total bilirubin, direct bilirubin, and indirect bilirubin throughout, as compared to ANIT group. The recorded reductions may reflect the role of Ech in helping bilirubin clearance from circulation as recorded by Ou et al (2016). Histopathological examination of liver sections confirmed our biochemical findings.…”

Chicken bile powder protects against α-naphthylisothiocyanate-induced cholestatic liver injury in mice

“…Traditional medicines and natural products have been widely used to treat cholestasis for thousands of years [ 22 – 24 ]. Dried black bear’s bile was recommended in China for the treatment of jaundice during the Tang dynasty (618-907 A.D.), as documented in the Tang Materia Medica, the first state pharmacopoeia [ 25 ].…”