Protective mechanism of glycyrrhizin on acute liver injury induced by carbon tetrachloride in mice
Protective mechanism of glycyrrhizin on acute liver injury induced by carbon tetrachloride in mice
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DOI：
10.1248/bpb.30.1898
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发表时间：
2007-10-01
影响因子：
2
通讯作者：
Lee, Sun-Mee
中科院分区：
文献类型：
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作者：
Lee, Chan-Ho;Park, Sang-Won;Lee, Sun-Mee
甘草素是从甘草（甘草）根中提取的主要活性成分，甘草是用于治疗肝脏疾病的最广泛使用的草药制剂之一。本研究评估了在四氯化碳（CCl 4）诱导的肝损伤小鼠模型中，野木瓜蛋白酶的潜在有益作用。小鼠腹腔注射CCl 4（0.5 ml/kg）。在给予CCl 4前24 h、0.5 h和给药后4 h给予甘草酸（50、100、200、400 mg/kg）。CCl_4处理后24 h，血清转氨酶活性和肝脏丙二醛水平显著升高，而还原型谷胱甘肽浓度降低。这些变化减弱了白藜芦醇。CCl_4使循环肿瘤坏死因子-α水平显著升高，而CCl_4使循环肿瘤坏死因子-α水平显著降低。肝诱导型一氧化氮合酶、环氧合酶-2和血红素氧合酶-1蛋白表达水平在CCl 4处理后显著升高。甘草甜素减少了诱导型一氧化氮和环氧合酶-2的这些变化，但血红素氧合酶-1的蛋白表达进一步升高，通过治疗甘草甜素。CCl 4增加肿瘤坏死因子-α、诱导型一氧化氮合酶、环氧化酶-2和血红素氧合酶-1 mRNA表达水平。血红素氧合酶-1的mRNA表达增加的治疗，而抑制肿瘤坏死因子-α，诱导型一氧化氮合酶，环氧合酶-2的mRNA表达的增加。这些结果表明，胡萝卜素减轻四氯化碳诱导的肝损伤，这种保护作用可能是由于血红素氧合酶-1的诱导和促炎介质的下调。
Glycyrrhizin is the major active component extracted from licorice (Glycyrrhiza glabra) roots, one of the most widely used herbal preparations for the treatment of liver disorders. This study evaluated the potential beneficial effect of glycyrrhizin in a mouse model of carbon tetrachloride (CCl4)-induced liver injury. The mice were treated intraperitoneally with CCl4 (0.5 ml/kg). They received glycyrrhizin (50, 100, 200, 400 mg/kg) 24 h and 0.5 h before and 4 h after administering CCl4. The serum activities of aminotransferase and the hepatic level of malondialdehyde were significantly higher 24 h after the CCl4, treatment, while the concentration of reduced glutathione was lower. These changes were attenuated by glycyrrhizin. CCl4 increased the level of circulating tumor necrosis factor-a markedly, which was reduced by glycyrrhizin. The levels of hepatic inducible nitric oxide synthase, cyclooxygenase-2, and heme oxygenase-1 protein expression were markedly higher after the CCl4 treat- ment. Glycyrrhizin diminished these alterations for inducible nitric oxide and cyclooxygenase-2 but the protein expression of heme oxygenase-1 was further elevated by the treatment of glycyrrhizin. CCl4 increased the level of tumor necrosis factor-alpha, inducible nitric oxide synthase, cyclooxygenase-2, and heme oxygenase-1 mRNA expressions. The mRNA expression of heme oxygenase-1 was augmented by the glycyrrhizin treatment, while glycyrrhizin attenuated the increase in tumor necrosis factor-alpha, inducible nitric oxide synthase, and cyclooxygenase-2 mRNA expressions. These results suggest that glycyrrhizin alleviates CCl4-induced liver injury, and this protection is likely due to the induction of heme oxygenase-1 and the downregulation of proinflammatory mediators.