Jo Yun Ho, Lee Hwan, Oh Myeong Hwan, Lee Gyeong Hee, Lee You Jin, Lee Ji Sun, Kim Min Jung, Kim Won Yong, Kim Jin Seong, Yoo Dae Seok, Cho Sang Won, Cha Seon Woo, Pyo Mi Kyung
International Ginseng & Herb Research Institute, Geumsan 32724, Korea.
Nutr Res Pract. 2020 Aug;14(4):334-351. doi: 10.4162/nrp.2020.14.4.334. Epub 2020 Apr 10.
BACKGROUND/OBJECTIVES: This study was designed to investigate the improvement effect of white ginseng extract (GS-KG9) on D-galactosamine (Ga1N)-induced oxidative stress and liver injury.
SUBJECTS/METHODS: Sixty Sprague-Dawley rats were divided into 6 groups. Rats were orally administrated with GS-KG9 (300, 500, or 700 mg/kg) or silymarin (25 mg/kg) for 2 weeks. The rats of the GS-KG9- and silymarin-treated groups and a control group were then intraperitoneally injected Ga1N at a concentration of 650 mg/kg for 4 days. To investigate the protective effect of GS-KG9 against GalN-induced liver injury, blood liver function indicators, anti-oxidative stress indicators, and histopathological features were analyzed.
Serum biochemical analysis indicated that GS-KG9 ameliorated the elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in GalN-treated rats. The hepatoprotective effects of GS-KG9 involved enhancing components of the hepatic antioxidant defense system, including glutathione, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT). In addition, GS-KG9 treatment inhibited reactive oxygen species (ROS) production induced by GalN treatment in hepatocytes and significantly increased the expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins, which are antioxidant proteins. In particular, by histological analyses bases on hematoxylin and eosin, Masson's trichrome, α-smooth muscle actin, and transforming growth factor-β1 staining, we determined that the administration of 500 mg/kg GS-KG9 inhibited hepatic inflammation and fibrosis due to the excessive accumulation of collagen.
These findings demonstrate that GS-KG9 improves GalN-induced liver inflammation, necrosis, and fibrosis by attenuating oxidative stress. Therefore, GS-KG9 may be considered a useful candidate in the development of a natural preventive agent against liver injury.
背景/目的:本研究旨在探讨白参提取物(GS-KG9)对D-半乳糖胺(GalN)诱导的氧化应激和肝损伤的改善作用。
对象/方法:将60只Sprague-Dawley大鼠分为6组。大鼠口服GS-KG9(300、500或700mg/kg)或水飞蓟宾(25mg/kg),持续2周。然后,将GS-KG9和水飞蓟宾处理组的大鼠以及一个对照组大鼠腹腔注射浓度为650mg/kg的GalN,持续4天。为了研究GS-KG9对GalN诱导的肝损伤的保护作用,分析了血液肝功能指标、抗氧化应激指标和组织病理学特征。
血清生化分析表明,GS-KG9改善了GalN处理大鼠中天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、碱性磷酸酶(ALP)和乳酸脱氢酶(LDH)的升高。GS-KG9的肝脏保护作用包括增强肝脏抗氧化防御系统的成分,包括谷胱甘肽、谷胱甘肽过氧化物酶(GPx)、超氧化物歧化酶(SOD)和过氧化氢酶(CAT)。此外,GS-KG9处理抑制了GalN处理诱导的肝细胞中活性氧(ROS)的产生,并显著增加了抗氧化蛋白核因子红系2相关因子2(Nrf2)和血红素加氧酶-1(HO-1)蛋白的表达水平。特别是,通过苏木精和伊红、Masson三色染色、α-平滑肌肌动蛋白和转化生长因子-β1染色的组织学分析,我们确定给予500mg/kg GS-KG9可抑制由于胶原蛋白过度积累引起的肝脏炎症和纤维化。
这些发现表明,GS-KG9通过减轻氧化应激改善了GalN诱导的肝脏炎症、坏死和纤维化。因此,GS-KG9可能被认为是开发肝脏损伤天然预防剂的有用候选物。