- 作者：Hao Chen1 ; Xiaotao Huang1 ; Jianbin Min ; Weirong Li ; Rong Zhang ; Wei Zhao ; athena_zw@126.com" class="auth_mail" title="E-mail the corresponding author ; Changhui Liu ; realliuch@126.com" class="auth_mail" title="E-mail the corresponding author ; Lang Yi ; Suiqing Mi ; Ningsheng Wang ; Qi Wang ; Chenchen Zhu
- 关键词：GPA ; Geniposidic acid ; ANIT ; α-naphthylisothiocyanate ; Fxr ; farnesoid X receptor ; Bsep ; bile salt export pump ; Mrp2 ; multidrug resistance associated protein2 ; GOT ; glutamic-Oxalacetic transaminase ; GPT ; glutamic pyruvic transaminase ; γ-GT ; γ-glutamyltranspeptidase ; TBA ; total bile acid ; TB ; total bilirubin ; DB ; direct bilirubin ; GSH ; glutathione ; UDA ; ursodeoxycholic acid ; RT-PCR ; reverse transcription polymerase chain reaction ; WB ; western blotting
- 刊名：Journal of Ethnopharmacology
- 出版年：2016
- 出版时间：17 February 2016
- 年：2016
- 卷：179
- 期：Complete
- 页码：197-207
- 全文大小：3560 K
Aim of the study
This investigation was designed to evaluate the hepatoprotection effect and potential mechanisms of GPA derived from Gardenia jasminoides Ellis (Rubiaceae) on fighting against α-naphthylisothiocyanate (ANIT) caused liver injury with acute intrahepatic cholestasis.
Materials and methods
Sprague-Dawley (SD) rats were intragastrically (i.g.) administered with the GPA (100, 50 and 25 mg/kg B.W. every 24 h) for seven consecutive days, and then they were treated with ANIT (i.g. 65 mg/kg once in the 5th day) which induced liver injury with acute intrahepatic cholestasis. Serum and bile biochemical analysis, bile flow rate and liver histopathology were measured to evaluate the protective effect of GPA fight against ANIT treatment. The protein and mRNA expression levels of farnesoid X receptor (Fxr), bile-salt export pump (Bsep), multidrug resistance associated protein2 (Mrp2), were evaluated to study the effect of liver protection about GPA against ANIT induced hepatotoxicity and underlying mechanisms.
Results
Some abnormalities were observed on ANIT treated rats including weight loss, reduced food intake and hair turned yellow. Obtained results demonstrated that at dose 100 and 50 mg/kg B.W. (P<0.01) and 25 mg/kg B.W. (P<0.05) of GPA pretreated dramatically prevented ANIT induced decreased in bile flow rate. Compared with ANIT treated group, the results of bile biochemical parameters about total bile acid (TBA) was increased by GPA at groups with any dose (P<0.01), glutathione (GSH) was increased significantly at high dose (P<0.01) and medium dose (P<0.05), total bilirubin (TB) was increased at high and medium dose (P<0.05), direct bilirubin (DB) was only increased at high dose (P<0.01). Serum levels of glutamic-Oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), γ-glutamyltranspeptidase (γ-GT), TB, DB and TBA in comparison with ANIT treated group (P<0.01) were reduced by GPA (between 100 and 50 mg/kg B.W.) pretreatment. Histopathology of the liver tissue showed that pathological damages and hepatic portal area filled with bile were relieved after GPA pretreatment compared with ANIT treated group. The protein and mRNA expression of Fxr, Bsep and Mrp2 were decreased in ANIT treated group. On the contrary, the protein and mRNA of Fxr, Bsep and Mrp2 were up regulated significantly pretreatment by GPA at dose of high and medium groups. On protein level of Bsep and Mrp2 the result shown no statistical difference in GPA (25 mg/kg B.W.), but it was not same shown in mRNA level.
Conclusion
The results of this investigation have demonstrated that the GPA exerts a dose dependent hepatoprotection effect on ANIT induced liver damage with acute intrahepatic cholestasis in rats, which may due to Fxr mediated regulation of bile transporters like Bsep and Mrp2.