Protective effects of ginsenoside-Rg2 and-Rh1 on liver function through inhibiting TAK1 and STAT3-mediated inflammatory activity and Nrf2/ARE-mediated antioxidant signaling pathway
Protective effects of ginsenoside-Rg2 and-Rh1 on liver function through inhibiting TAK1 and STAT3-mediated inflammatory activity and Nrf2/ARE-mediated antioxidant signaling pathway
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DOI：
10.1007/s12272-020-01304-4
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发表时间：
2021-02-03
影响因子：
6.7
通讯作者：
Heo, Kyung-Sun
中科院分区：
文献类型：
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作者：
Nguyen, Thuy Le Lam;Huynh, Diem Thi Ngoc;Heo, Kyung-Sun
全身或肝脏炎症是由腹腔内应用脂多糖（LPS）引起的。在本研究中，我们研究了人参皂苷- rg2 （G-Rg2）和-Rh1 （G-Rh1）联合使用对LPS刺激下肝功能的抗炎和抗氧化作用。我们首先证实了100 μ g/ml的g - rg2和-Rh1对HepG2细胞没有细胞毒性。G-Rg2和-Rh1处理显著抑制了巨噬细胞中STAT3和TAK1的激活，以及iNOS、tnf - α和IL-1 β等炎症因子的激活。在HepG2细胞中，G-Rg2和-Rh1处理抑制STAT3和TAK1/c-Jun n末端激酶的激活，下调NF-kappa B转录因子的核易位。此外，通过G-Rg2和-Rh1处理，lps诱导的线粒体功能障碍得以恢复。有趣的是，G-Rg2和-Rh1预处理可有效抑制LPS刺激诱导的线粒体损伤介导的ROS产生，Nrf2核易位和ARE启动子活性的改变参与了G-Rg2和-Rh1平衡ROS水平的作用。在lps处理的小鼠肝组织中，G-Rg2和-Rh1处理保护肝损伤，增加Nrf2表达，降低CD45表达。综上所述，G-Rg2和-Rh1通过Nrf2增加抗氧化作用，通过肝细胞和巨噬细胞STAT3/TAK1和NF-kappa B信号通路增加抗炎活性，对肝功能起保护作用。
Systemic or hepatic inflammation is caused by intraperitoneal application of lipopolysaccharide (LPS). In this study, we investigated anti-inflammatory and antioxidant properties of combination of ginsenoside-Rg2 (G-Rg2) and -Rh1 (G-Rh1) on liver function under LPS challenging. We first confirmed that G-Rg2 and -Rh1 at 100 mu g/ml did not show cytotoxicity in HepG2 cells. G-Rg2 and -Rh1 treatment significantly inhibited activation of STAT3 and TAK1, and inflammatory factors including iNOS, TNF-alpha, and IL-1 beta in peritoneal macrophages. In HepG2 cells, G-Rg2 and -Rh1 treatment inhibited activation of STAT3 and TAK1/c-Jun N-terminal kinase, and down-regulated nuclear translocation of NF-kappa B transcription factor. In addition, LPS-induced mitochondrial dysfunction was restored by treatment with G-Rg2 and -Rh1. Interestingly, pretreatment with G-Rg2 and -Rh1 effectively inhibited mitochondrial damage-mediated ROS production induced by LPS stimulation, and alterations of Nrf2 nuclear translocation and ARE promotor activity were involved in G-Rg2 and -Rh1 effects on balancing ROS levels. In liver tissues of LPS-treated mice, G-Rg2 and -Rh1 treatment protected liver damages and increased Nrf2 expression while reducing CD45 expression. Taken together, G-Rg2 and -Rh1 exerts a protective effect on liver function by increasing antioxidant through Nrf2 and anti-inflammatory activities through STAT3/TAK1 and NF-kappa B signaling pathways in liver cells and macrophages.