Andrographolide ameliorates d-galactosamine/lipopolysaccharide-induced acute liver injury by activating Nrf2 signaling pathway.
Andrographolide ameliorates d-galactosamine/lipopolysaccharide-induced acute liver injury by activating Nrf2 signaling pathway.
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DOI：
10.18632/oncotarget.17149
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发表时间：
2017-06-20
期刊：
影响因子：
--
通讯作者：
Xu CL
中科院分区：
文献类型：
--
作者：
Pan CW;Yang SX;Pan ZZ;Zheng B;Wang JZ;Lu GR;Xue ZX;Xu CL
穿心莲内酯 (ADH) 是从穿心莲中提取的一种二萜内酯，已被发现具有抗炎和抗氧化作用。然而，其对肝损伤的保护作用和机制尚未明确。本研究试图揭示ADH对脂多糖（LPS）和D-半乳糖胺（D-GalN）诱导的小鼠急性肝损伤的保护作用及机制。 LPS(60 mg/kg)和D-GalN(800 mg/kg)诱导小鼠肝损伤模型，LPS和D-GalN治疗1 h后给予ADH。通过H&E染色测量肝组织组织学。采用检测试剂盒检测血清丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）水平。采用ELISA法检测TNF-α、IL-1β水平。此外，还检测了丙二醛（MDA）和活性氧（ROS）含量。同时，Western blot检测Nrf2、HO-1、NF-κB的表达。结果表明，ADH治疗可改善肝脏组织学，并以剂量依赖性方式降低肝组织的ALT、AST、MPO、IL-1β、TNF-α水平以及MDA和ROS水平。 ADH 还抑制 LPS/D-GalN 诱导的 NF-κB 激活。 ADH处理增加了Nrf2和HO-1的表达。总之，ADH 通过抑制 NF-κB 和激活 Nrf2 信号通路来防止 LPS/D-GalN 诱导的肝损伤。
Andrographolide (ADH), a diterpenoid lactone extracted from Andrographis paniculata, has been found to have anti-inflammatory and anti-oxidative effects. However, its protective effects and mechanisms on liver injury have not been investigated clearly. This study takes an attempt to reveal the protective effects and mechanism of ADH on lipopolysaccharide (LPS) and D-galactosamine (D-GalN)-induced acute liver injury in mice. The mice liver injury model was induced by LPS (60 mg/kg) and D-GalN (800 mg/kg), and ADH was given 1 h after LPS and D-GalN treatment. Hepatic tissue histology was measured by H&E staining. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected by detection kits. The levels of TNF-α and IL-1β were detected by ELISA. Moreover, malondialdehyde (MDA) and reactive oxygen species (ROS) contents were also detected. Meanwhile, the expression of Nrf2, HO-1, and NF-κB were detected by western blot analysis. The results showed that ADH treatment improved liver histology and decreased the levels of ALT, AST, MPO, IL-1β, TNF-α, as well as MDA and ROS levels of hepatic tissues in a dose-dependent manner. ADH also inhibited LPS/D-GalN-induced NF-κB activation. The expression of Nrf2 and HO-1 were increased by treatment of ADH. In conclusion, ADH protected against LPS/D-GalN-induced liver injury by inhibiting NF-κB and activating Nrf2 signaling pathway.
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影响因子：
6.3
作者：
Lee, W.;Ku, S.;Bae, J.
通讯作者：
Bae, J.
影响因子：
5.4
作者：
Lee, Ko-Chen;Chang, Hen-Hong;Lee, Tzung-Yan
通讯作者：
Lee, Tzung-Yan
影响因子：
3.8
作者：
Jiang T;Huang Z;Chan JY;Zhang DD
通讯作者：
Zhang DD
影响因子：
29.4
作者：
Lamle, Jutta;Marhenke, Silke;Vogel, Arndt
通讯作者：
Vogel, Arndt
DOI：
10.1152/ajpregu.2000.278.5.r1202
发表时间：
2000-05-01
影响因子：
2.8
作者：
Nowak, M;Gaines, GC;Moldawer, LL
通讯作者：
Moldawer, LL