Laboratory of Liver Regeneration, Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju 561-712, Korea.
J Nat Prod. 2012 Oct 26;75(10):1683-9. doi: 10.1021/np300099a. Epub 2012 Oct 1.
In this study the protective effects of davallialactone (1), isolated from Inonotus xeranticus, have been examined against carbon tetrachloride (CCl₄-induced acute liver injury. Mice received subcutaneous injection of 1 (2.5, 5, and 10 mg/kg) for three days before CCl₄ injection (1 mg/kg). Protection from liver injury by 1 was confirmed by the observation of decreased serum transaminases and diminished necrosis of liver tissue. Reduced hepatic injury was very similar to that observed with silymarin, a known hepatoprotective drug used in this work for comparison. The groups treated with 1 had reduced reactive oxygen species (ROS), reduced serum malonyldialdehyde levels, and increased levels of liver Cu/Zn superoxide dismutase, as compared to the CCl₄ control group. The expression of heme oxygenase-1 in the liver tissue was increased and the activity of liver cytochrome P4502E1 was restored in the mice treated with 1. In addition, levels of serum tumor necrosis factor-alpha (TNF-α), inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2), numbers of macrophage, and cleaved caspase-3-positive hepatocytes were reduced in the groups treated with 1. These findings suggest that davallialactone has protective effects against CCl₄-induced acute liver injury, and this protection is likely due to the suppression of ROS-induced lipid peroxidation and inflammatory response.
在这项研究中，从桦褐孔菌中分离得到的桦褐孔菌素（1）对四氯化碳（CCl₄）诱导的急性肝损伤的保护作用进行了研究。小鼠在 CCl₄（1mg/kg）注射前连续三天接受皮下注射 1（2.5、5 和 10mg/kg）。1 对肝损伤的保护作用通过观察血清转氨酶的降低和肝组织坏死的减少得到证实。与用作比较的已知保肝药物水飞蓟素观察到的结果非常相似。与 CCl₄ 对照组相比，用 1 处理的组的活性氧（ROS）减少，血清丙二醛水平降低，肝脏铜/锌超氧化物歧化酶水平升高。与 CCl₄ 对照组相比，1 处理的小鼠肝组织血红素加氧酶-1（HO-1）的表达增加，肝细胞色素 P4502E1 的活性恢复。此外，用 1 处理的组的血清肿瘤坏死因子-α（TNF-α）、诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2）水平、巨噬细胞数量和 cleaved caspase-3 阳性肝细胞减少。这些发现表明，桦褐孔菌素对 CCl₄ 诱导的急性肝损伤具有保护作用，这种保护作用可能是由于抑制了 ROS 诱导的脂质过氧化和炎症反应。
