Clinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China; Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Chem Biol Interact. 2020 Jun 1;324:109062. doi: 10.1016/j.cbi.2020.109062. Epub 2020 Mar 18.
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.
人参皂苷 Rg1 是从人参根中提取的一种有效成分，本研究采用α-萘异硫氰酸酯（ANIT）诱导的大鼠肝内胆汁淤积模型，探讨 Rg1 对胆汁淤积的保护作用。48 只雄性 SD 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（10mg/kg）、中剂量 Rg1 组（20mg/kg）和高剂量 Rg1 组（40mg/kg）。然后，模型组、UDCA 组和所有 Rg1 组大鼠灌胃给予 80mg/kg ANIT，对照组给予等体积橄榄油。观察肝组织的病理变化，测量胆管胆汁分泌，定量检测血清生化标志物，包括丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、碱性磷酸酶（ALP）、谷氨酰转肽酶（GTP）和总胆红素（TBIL）、直接胆红素（DBIL）、总胆汁酸（TBA）。定量检测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）。定量检测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）、转运体和代谢酶的表达。Rg1 治疗改善了肝组织的病理损伤，促进了胆汁分泌，显著降低了血清中胆汁淤积标志物 ALT、AST、ALP、GTP、TBIL、DBIL 和 TBA 的水平。Rg1 增加了肝匀浆中 SOD 和 GSH-Px 的活性，同时降低了血清中 MDA 和炎症介质的水平。Rg1 还调节了 FXR、胆汁酸转运体和代谢酶的表达。总的来说，Rg1 通过改善胆汁分泌和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 的激活和肝转运体和代谢酶的调节有关。
