Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, China.
J Pharmacol Sci. 2010;114(2):147-57. doi: 10.1254/jphs.10045fp. Epub 2010 Sep 11.
The hepatoprotective effects of sarmentosin-containing extracts of Sedum sarmentosum (SS) in D-galactosamine (D-GalN) / lipopolysaccharide (LPS)-induced fulminant hepatic failure mouse model. Pretreatment with SS markedly protected mice from lethal liver injury, which has known to be associated with an abrupt elevation of serum tumor necrosis factor (TNF)-α level. Indeed, SS significantly blocked the elevation of TNF-α and alanine aminotransferase and aspartate aminotransferase as well. SS also remarkably reduced number of apoptotic hepatocytes and DNA fragmentation in the liver, which correlated with blockade of caspase-3 activation. In addition, SS suppressed the increased expression of toll-like receptor 4 (TLR4). The activation of c-Jun NH(2)-terminal kinase, extracellular signal-regulated kinase, and p38 induced by D-GalN/LPS was also significantly suppressed by SS treatment. Furthermore, SS significantly inhibited the activation of nuclear factor-κB. In RAW 264.7 cells stimulated with LPS, TNF-α release and TLR4 expression was suppressed by SS pretreatment, which was in line with in vivo results. These findings suggested that SS prevents D-GalN/LPS-induced fulminant hepatic failure, and this protection is likely associated with its anti-apoptotic activity and the down-regulation of mitogen activated protein kinase activity associated at least in part with suppressing the transcription of LPS receptors.
含有垂盆草提取物的肝保护作用 （SS） 在半乳糖胺（D-GalN）/脂多糖（LPS）诱导的暴发性肝衰竭小鼠模型。预处理与 SS 明显保护小鼠致命性肝损伤，这已被证明与血清肿瘤坏死因子（TNF）-α水平的急剧升高有关。事实上，SS 显著阻断了 TNF-α和丙氨酸氨基转移酶和天冬氨酸氨基转移酶的升高。SS 还明显减少了凋亡的肝细胞和肝 DNA 片段的数量，这与阻断 caspase-3 的激活有关。此外，SS 抑制了 Toll 样受体 4（TLR4）的表达增加。SS 处理还显著抑制了半乳糖胺/脂多糖诱导的 c-Jun NH（2）-末端激酶、细胞外信号调节激酶和 p38 的激活。此外，SS 显著抑制了核因子-κB 的激活。在 LPS 刺激的 RAW 264.7 细胞中，SS 预处理抑制了 TNF-α的释放和 TLR4 的表达，这与体内结果一致。这些发现表明，SS 可预防 D-GalN/LPS 诱导的暴发性肝衰竭，这种保护作用可能与其抗凋亡活性有关，并下调与至少部分抑制 LPS 受体转录相关的丝裂原激活蛋白激酶活性。
