Protective effects of ginsenoside Rg1 against lipopolysaccharide/D-galactosamine-induced acute liver injury in mice through inhibiting toll-like receptor 4 signaling pathway
Protective effects of ginsenoside Rg1 against lipopolysaccharide/D-galactosamine-induced acute liver injury in mice through inhibiting toll-like receptor 4 signaling pathway
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DOI：
10.1016/j.intimp.2018.06.008
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发表时间：
2018-08-01
影响因子：
5.6
通讯作者：
Liu, Kexin
中科院分区：
文献类型：
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作者：
Ning, Chenqing;Gao, Xiaoguang;Liu, Kexin
急性肝损伤（ALI）是一种严重的肝脏疾病，其特征是肝脏大面积炎症。本研究旨在探讨人参中的生物活性成分人参皂苷Rg1（Rg1）对脂多糖/D-半乳糖胺（LPS/D-GalN）诱导的小鼠ALI的保护作用，同时探讨体内外的分子机制。在给予LPS（40μg/kg）/D-GalN（700mg/kg）之前，用Rg1对小鼠进行预处理三天。结果表明，Rg1 提高了小鼠的存活率并降低了肝脏与体重的比率。 Rg1 还可以减少 LPS/D-GalN 诱导的氧化标记物（如 MDA 和 MPO）的产生。此外，Rg1显着减少炎症细胞因子的产生，包括TNF-α、IL-6、IL-1β、Mip-2、Mcp-1、iNOS，并增加抗炎细胞因子IL-10的活性。此外，Rg1抑制TLR4及其下游基因（包括NF-κB和MAPK）的蛋白表达，这些基因参与炎症反应。 Rg1 通过调节外排转运蛋白 Mrp2 和各种酶（包括 GCLC、GCLM、HO-1 和 NQO1）的表达，显着降低氧化应激。然而，Rg1 诱导的这些基因和蛋白质的变化在体外被 TLR4 拮抗剂 TAK-242 消除。总之，Rg1对LPS/D-GalN诱导的小鼠ALI具有保肝作用。这种保护作用可能与 TLR4 的抑制有关。这些发现表明 Rg1 可能是预防 ALI 的有前途的药物。
Acute liver injury (ALI) is a dramatic liver disease characterized by large areas of inflammation in the liver. This study aimed to investigate the protective effects of ginsenoside Rg1 (Rg1), a biologically active component in Panax ginseng, on lipopolysaccharide/D-galactosamine (LPS/D-GalN)-induced ALI in mice, and meanwhile explore the molecular mechanism in vivo and in vitro. Mice were pretreated with Rg1 for three days prior to LPS (40 mu g/kg)/D-GalN (700 mg/kg) administration. The results showed that Rg1 improved the survival rate and reduced the liver to body weight ratios in mice. Rg1 also reduced the production of oxidative markers such as MDA and MPO induced by LPS/D-GalN. In addition, Rg1 significantly decreased the production of inflammatory cytokines including TNF-alpha, IL-6, IL-1 beta, Mip-2, Mcp-1, iNOS, and increased the activity of anti-inflammatory cytokine IL-10. Moreover, Rg1 inhibited the protein expression of TLR4 and its downstream genes including NF-kappa B and MAPKs, which are involved in inflammatory response. Rg1 dramatically reduced oxidative stress by regulating the expression of efflux transporters Mrp2 and various enzymes including GCLC, GCLM, HO-1 and NQO1. However, the changes in these genes and protein induced by Rg1 were abrogated by TLR4 antagonist TAK-242 in vitro. In conclusion, Rg1 had hepatoprotective effect on LPS/D-GalN-induced ALI in mice. The protection may be associated with the inhibition of TLR4. These findings suggest that Rg1 may be a promising agent for prevention against ALI.