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Ginsenoside Rg1 alleviates ANIT-induced intrahepatic cholestasis in rats via activating farnesoid X receptor and regulating transporters and metabolic enzymes.
Chemico-Biological Interactions ( IF 4.7 ) Pub Date : 2020-03-18 , DOI: 10.1016/j.cbi.2020.109062
Qing Xiao 1 , Shujun Zhang 2 , Huina Ren 3 , Ruoyang Du 4 , Jiajun Li 2 , Jinqiu Zhao 2 , Yue Gao 2 , Yali Zhu 2 , Wenxiang Huang 2
Affiliation  

Ginsenoside Rg1 is an active ingredient extracted from the roots of ginsenoside, and an α-naphthylisothiocyanate (ANIT)-induced rat model of intrahepatic cholestasis was used to investigate the protective effect of Rg1 on cholestasis. 48 SD male rats were randomly divided into 6 groups: control group, model group, UDCA group (ursodeoxycholic acid), low-dose Rg1 group (10 mg/kg), medium-dose Rg1 group (20 mg/kg) and high-dose Rg1 group (40 mg/kg). The model group, the UDCA group and all the Rg1 group were then intragastrically administered with 80 mg/kg ANIT, and the control group were given equal volume of olive oil. Then the pathological changes in liver tissue were observed, the secretion of bile in the bile duct was measured, and the biochemical markers in serum were quantified, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), glutamyl transfer peptidase (GTP) and the content of total bilirubin (TBIL), direct bilirubin (DBIL), total bile acid (TBA). The contents of inflammatory mediators in serum were quantified, including tumor necrosis factor (TNF-α), γ-interferon (IFN-γ) and interleukin-1β (IL-1β). The contents of superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) in liver homogenate were quantified. Expression of farnesoid X receptor (FXR), transporters and metabolic enzymes in liver tissue was monitored. Rg1 treatment improved liver tissue pathological damage, promoted bile secretion and significantly reduced serum levels of the intrahepatic cholestasis markers ALT, AST, ALP, GTP, TBIL, DBIL and TBA. Rg1 increased the activity of SOD and GSH-Px in liver homogenate, while, reducing the serum levels of MDA and inflammatory mediators. Rg1 also regulated the expression of FXR, bile acid transporters and metabolic enzymes. Overall, Rg1 alleviated liver injury by improving secretion of bile and normalizing the activity of enzymes in the serum. The protective mechanism appeared to be related to the activation of FXR and regulation of liver transporters and metabolic enzymes.

中文翻译:

人参皂苷 Rg1 通过激活法尼醇 X 受体并调节转运蛋白和代谢酶来减轻 ANIT 诱导的大鼠肝内胆汁淤积。

人参皂苷Rg1是从人参皂苷根中提取的活性成分,采用α-萘基异硫氰酸酯(ANIT)诱导的大鼠肝内胆汁淤积模型研究Rg1对胆汁淤积的保护作用。48只SD雄性大鼠随机分为6组:对照组、模型组、UDCA组(熊去氧胆酸)、低剂量Rg1组(10 mg/kg)、中剂量Rg1组(20 mg/kg)和高剂量组。剂量Rg1组(40mg/kg)。模型组、UDCA组及Rg1组均按80 mg/kg ANIT灌胃,对照组给予等体积橄榄油。观察肝组织病理变化,测定胆管胆汁分泌情况,定量血清生化标志物,包括丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)、谷氨酰转移肽酶(GTP)和总胆红素(TBIL)、直接胆红素(DBIL)、总胆汁酸(TBA)的含量。定量血清中炎症介质的含量,包括肿瘤坏死因子(TNF-α)、γ-干扰素(IFN-γ)和白细胞介素-1β(IL-1β)。定量肝匀浆中超氧化物歧化酶(SOD)、丙二醛(MDA)和谷胱甘肽过氧化物酶(GSH-Px)的含量。监测肝组织中法尼醇X受体(FXR)、转运蛋白和代谢酶的表达。Rg1治疗改善肝组织病理损伤,促进胆汁分泌,显着降低肝内胆汁淤积标志物ALT、AST、ALP、GTP、TBIL、DBIL和TBA的血清水平。Rg1增加肝匀浆中SOD和GSH-Px的活性,同时降低血清MDA和炎症介质的水平。Rg1 还调节 FXR、胆汁酸转运蛋白和代谢酶的表达。总体而言,Rg1 通过改善胆汁分泌并使血清中酶的活性正常化来减轻肝损伤。保护机制似乎与 FXR 的激活以及肝脏转运蛋白和代谢酶的调节有关。
更新日期:2020-03-19
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