Hepatoprotective activity of berberine is mediated by inhibition of TNF-α, COX-2, and iNOS expression in CCl4-intoxicated mice
Hepatoprotective activity of berberine is mediated by inhibition of TNF-α, COX-2, and iNOS expression in CCl4-intoxicated mice
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DOI：
10.1016/j.tox.2010.11.005
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发表时间：
2011-02-04
期刊：
影响因子：
4.5
通讯作者：
Blagojevic, Gordana
中科院分区：
文献类型：
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作者：
Domitrovic, Robert;Jakovac, Hrvoje;Blagojevic, Gordana
本研究探讨了异喹啉生物碱小檗碱对 CCl4 诱导的小鼠肝毒性的保护作用。在注射 CCl4（10%，v/v 橄榄油，2 ml/kg）前 1 小时，以单剂量 5 和 10 mg/kg 腹膜内 (i.p.) 施用小檗碱，24 小时后对小鼠实施安乐死。小檗碱以浓度依赖性方式显着抑制 CCl4 中毒小鼠血清丙氨酸转氨酶 (ALT)、天冬氨酸转氨酶 (AST) 和碱性磷酸酶 (ALP) 水平的升高。小檗碱可显着防止超氧化物歧化酶（Cu/Zn SOD）肝脏活性的降低和脂质过氧化的增加。 10 mg/mg 小檗碱可减少组织病理学变化，并显着减弱肿瘤坏死因子-α (INF-α)、环氧合酶-2 (COX-2) 和诱导型一氧化氮合酶 (iNOS) 的表达。这项研究的结果表明，小檗碱可以有效保护肝脏免受四氯化碳引起的急性损伤。小檗碱的保肝机制可能与清除自由基、减轻氧化/亚硝化应激以及抑制肝脏炎症反应有关。 (C) 2010 Elsevier Ireland Ltd. 保留所有权利。
This study investigated the protective effects of isoquinoline alkaloid berberine on the CCl4-induced hepatotoxicity in mice. Berberine was administered as a single dose at 5 and 10 mg/kg intraperitoneally (i.p.), 1 h before CCl4 (10%, v/v in olive oil, 2 ml/kg) injection and mice were euthanized 24h later. The rise in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in CCl4-intoxicated mice was markedly suppressed by berberine in a concentration-dependent manner. The decrease in hepatic activity of superoxide dismutase (Cu/Zn SOD) and an increase in lipid peroxidation were significantly prevented by berberine. Histopathological changes were reduced and the expression of tumor necrosis factor-alpha (INF-alpha), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) was markedly attenuated by berberine 10 mg/mg. The results of this study indicate that berberine could be effective in protecting the liver from acute CCl4-induced injury. The hepatoprotective mechanisms of berberine may be related to the free radical scavenging and attenuation of oxidative/nitrosative stress, as well as to the inhibition of inflammatory response in the liver. (C) 2010 Elsevier Ireland Ltd. All rights reserved.