Target profiling analyses of bile acids in the evaluation of hepatoprotective effect of gentiopicroside on ANIT-induced cholestatic liver injury in mice.
Keywords
Abstract
BACKGROUND
Gentiopicroside (GPS), one of iridoid glucoside representatives, is the most potential active component in Gentiana rigescens Franch. ex Hemsl and Gentiana macrophylla Pall. These two herbs have been used to treat jaundice and other hepatic and billiary diseases in traditional Chinese medicine for thousands of years.
OBJECTIVE
This study aimed to investigate the protective effects and mechanisms of GPS on α-naphthylisothiocyanate (ANIT) induced cholestatic liver injury in mice.
METHODS
Mice were treated with GPS (130mg/kg, ig) for 5 consecutive days. On the third day, mice were given a single dose of Alpha-naphthylisothiocyanate (75mg/kg, ig). Serum biochemical markers and individual bile acids in serum, liver, urine and feces were measured at different time points after ANIT administration. The expression of hepatic bile acid synthesis, uptake and transporter genes as well as ileum bile acid transporter genes were assayed.
RESULTS
In this study, ANIT exposure resulted in serious cholestasis with liver injury, which was demonstrated by dramatically increased serum levels of ALT, ALP, TBA and TBIL along with TCA CA, MCAs and TMCAs accumulation in both liver and serum. Furthermore, ANIT significantly decreased bile acid synthesis related gene expressions, and increased expression of bile acid transporters in liver. Continuous treatment with GPS attenuated ANIT-induced acute cholestasis as well as liver injury and correct the dyshomeostasis of bile acids induced by ANIT. Our data showed that GPS significantly upregulated the hepatic mRNA levels of synthesis enzymes (Cyp8b1 and Cyp27a1) and transporters (Mrp4 Mdr1 and Ost-β) as well as ileal bile acid circulation mediators (Asbt and Fgf15), accompanied by serum and hepatic bile acid levels decrease and further urinary and fecal bile acid levels increase.
CONCLUSIONS
GPS can change bile acids metabolism which highlights its importance in mitigating cholestasis, resulting in the marked decrease of intracellular bile acid pool back toward basal levels. And the protective mechanism was associated with regulation of bile acids-related transporters, but the potential mechanism warrants further investigation.
