Atractylodin ameliorates lipopolysaccharide and D-galactosamine-induced acute liver failure via the suppression of inflammation and oxidative stress
Atractylodin ameliorates lipopolysaccharide and D-galactosamine-induced acute liver failure via the suppression of inflammation and oxidative stress
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DOI：
10.1016/j.intimp.2019.04.005
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发表时间：
2019-07-01
影响因子：
5.6
通讯作者：
An, Beiying
中科院分区：
文献类型：
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作者：
Lyu, Zheng;Ji, Xufeng;An, Beiying
白藜芦醇苷（ACD）具有抗菌、抗炎、保肝等多种生物学和药理学活性。然而，ACD对脂多糖（LPS）和D-氨基半乳糖（GalN）诱导的急性肝衰竭（ALF）的保护作用以及潜在的分子机制尚不清楚。本研究结果表明，ACD治疗可降低ALF的高致死率，降低血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、单核细胞趋化蛋白（MCP）-1、白细胞介素-1 β（IL-1 β）、IL-6和肿瘤坏死因子-α（TNF-α）水平，改善ALF的病理性肝损伤。此外，ACD预处理抑制Toll样受体4（TLR4）、核因子κ B（NF-κ B）、丝裂原活化蛋白激酶（MAPK）和NOD样受体蛋白3（NLRP 3）活化途径。此外，我们的研究表明，ACD可以显著增加超氧化物歧化酶（SOD）和谷胱甘肽（GSH）的产生，并通过上调抗氧化酶血红素氧合酶-1（HO-1）和醌（NQO 1）的表达来减少考克斯-2、诱导型一氧化氮合酶（iNOS）、活性氧（ROS）和丙二醛（MDA）的产生。这与诱导核转录因子2（Nrf2）核转位有关。这些结果表明，ACD具有抗炎活性，其机制可能与下调NLRP 3炎症体和TLR 4-NF-κ B/-MAPK信号通路，抑制炎症介质的产生有关; ACD的抗氧化作用可能与上调Nrf2信号通路，激活GSH和SOD有关。
Atractylodin (ACD) possesses versatile biological and pharmacological activities, including antibacterial, anti-inflammatory and hepatoprotective properties. However, the protective effects of ACD on lipopolysaccharide (LPS) and D-galactosamine (GalN)-induced acute liver failure (ALF) as well as the underlying molecular mechanisms remain unclear. In this study, our findings showed that ACD treatment could reduce the high lethality rate; decrease the serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST), monocyte chemoattractant protein (MCP)-1, interleukin-1 beta (IL-1 beta), IL-6 and tumor necrosis factor-alpha (TNF-alpha), and ameliorate the pathological hepatic damage of ALF. Furthermore, ACD pretreatment inhibited toll like receptor 4 (TLR4), nuclear factor kappa B (NF-kappa B), the mitogen-activated protein kinase (MAPK) and NOD-like receptor protein-3 (NLRP3) activation pathway. Moreover, our research showed that ACD could dramatically increase superoxide dismutase (SOD) and glutathione (GSH) production, and reduce COX-2, inducible nitric oxide synthase (iNOS), reactive oxygen species (ROS) and malondialdehyde (MDA) production through upregulating the expression of the anti-oxidative enzymes heme oxygenase-1 (HO-1) and quinone (NQO1), which were related to the induction of nuclear transcription factor 2 (Nrf2) nuclear translocation. These results indicated that ACD exhibited anti-inflammatory activity, which was associated with the inhibition of inflammatory mediator production via the downregulation of the NLRP3 inflammasome and TLR4-NF-kappa B/-MAPK signaling pathways, and the antioxidative effects of ACD were connected with GSH and SOD activation through upregulation of the Nrf2-mediated signaling pathways.