Ursolic acid protects mouse liver against CCl4-induced oxidative stress and inflammation by the MAPK/NF-κB pathway
Ursolic acid protects mouse liver against CCl4-induced oxidative stress and inflammation by the MAPK/NF-κB pathway
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DOI：
10.1016/j.etap.2014.03.011
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发表时间：
2014-05-01
影响因子：
4.3
通讯作者：
Liu, Chan-Min
中科院分区：
文献类型：
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作者：
Ma, Jie-Qiong;Ding, Jie;Liu, Chan-Min
熊果酸（UA）是一种天然五环三萜类化合物，具有多种药理作用。然而，其对四氯化碳（CCl 4）诱导的肝毒性的保护作用尚未阐明。本研究的目的是研究UA对CCl 4处理的小鼠肝脏氧化应激和炎症的影响。雄性ICR小鼠注射CCl 4，联合或不联合UA给药（25和50 mg/kg，每日一次灌胃），持续一周。我们的数据表明，UA显着防止四氯化碳诱导的肝毒性的剂量依赖性的方式，肝损伤的诊断指标（血清转氨酶活性）和组织病理学分析表明。此外，四氯化碳诱导的活性氧（ROS）的产生和氧化应激，证明了脂质过氧化水平的增加和总抗氧化能力（TAC）水平的消耗，深刻的海拔与UA治疗抑制。此外，蛋白质印迹分析表明，UA显着降低CYP 2 E1的表达水平和生产的促炎标志物，包括TNF-α，IL-β和考克斯-2在四氯化碳处理的小鼠肝脏。在探索UA作用的潜在机制中，我们发现UA降低了CCl 4处理小鼠肝脏中丝裂原活化蛋白激酶（JNK，p38 MAPK，ERK）的活化，这反过来又使免疫调节转录因子核因子κ B（NF-κ B B）失活。总之，这些结果表明，UA抑制CCl 4诱导的炎症至少部分是由于其抗氧化活性和调节MAPK和NF-κ B信号通路的能力。(C)2014爱思唯尔有限公司版权所有。
Ursolic acid (UA), a natural pentacyclic triterpenoid, has been reported to have many benefits and medicinal properties. However, its protective effects against carbon tetrachloride (CCl4) induced hepatotoxicity have not been clarified. The aim of the present study was to investigate the effects of UA on oxidative stress and inflammation in liver of CCl4 treated mice. Male ICR mice were injected with CCl4 with or without UA co-administration (25 and 50 mg/kg intragastrically once daily) for one week. Our data showed that UA significantly prevented CCl4-induced hepatotoxicity in a dose-dependent manner, indicated by both diagnostic indicators of liver damage (serum aminotransferase activities) and histopathological analysis. Moreover, CCl4-induced profound elevation of reactive oxygen species (ROS) production and oxidative stress, as evidenced by increasing of lipid peroxidation level and depleting of the total antioxidant capacity (TAC) level in liver, were suppressed by treatment with UA. Furthermore, western blot analysis showed that UA significantly decreased CYP2E1 expression levels and production of pro-inflammatory markers including TNF-alpha, IL-beta and COX-2 in CCl4-treated mouse liver. In exploring the underlying mechanisms of UA action, we found that UA decreased the activation of mitogen-activated protein kinases (JNK, p38 MAPK, ERK), which in turn inactivated the immunoregulatory transcription factor nuclear factor kappa B (NF-kappa B) in liver of CCl4 treated mice. In conclusion, these results suggested that the inhibition of CCl4-induced inflammation by UA is due at least in part to its anti-oxidant activity and its ability to modulate the MAPK and NF-kappa B signaling pathway. (C) 2014 Elsevier B.V. All rights reserved.