Song Ya-Nan, Dong Shu, Wei Bin, Liu Ping, Zhang Yong-Yu, Su Shi-Bing
Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
E-institutes of Traditional Chinese Internal Medicine, Shanghai Municipal Education Commission, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
PLoS One. 2017 Mar 14;12(3):e0173598. doi: 10.1371/journal.pone.0173598. eCollection 2017.
To investigate mechanisms and altered pathways of gypenoside against carbon tetrachloride (CCl4)-induced liver fibrosis based on integrative analysis of proteomics and metabolomics data.
CCl4-induced liver fibrosis rats were administrated gypenoside. The anti-fibrosis effects were evaluated by histomorphology and liver hydroxyproline (Hyp) content. Protein profiling and metabolite profiling of rats liver tissues were examined by isobaric tags for relative and absolute quantitation (iTRAQ) approach and gas chromatography-mass spectrometer (GC-MS) technology. Altered pathways and pivotal proteins and metabolites were searched by integrative analysis of proteomics and metabolomics data. The levels of some key proteins in altered pathways were determined by western blot.
Histopathological changes and Hyp content in gypenoside group had significant improvements (P<0.05). Compared to liver fibrosis model group, we found 301 up-regulated and 296 down-regulated proteins, and 9 up-regulated and 8 down-regulated metabolites in gypenoside group. According to integrative analysis, some important pathways were found, including glycolysis or gluconeogenesis, fructose and mannose metabolism, glycine, serine and threonine metabolism, lysine degradation, arginine and proline metabolism, glutathione metabolism, and sulfur metabolism. Furthermore, the levels of ALDH1B1, ALDH2 and ALDH7A1 were found increased and restored to normal levels after gypenoside treated (P<0.05).
Gypenoside inhibited CCl4-induced liver fibrosis, which may be involved in the alteration of glycolysis metabolism and the protection against the damage of aldehydes and lipid peroxidation by up-regulating ALDH.
基于蛋白质组学和代谢组学数据的综合分析，研究绞股蓝总皂苷抗四氯化碳（CCl4）诱导肝纤维化的机制及通路变化。
对CCl4诱导的肝纤维化大鼠给予绞股蓝总皂苷。通过组织形态学和肝脏羟脯氨酸（Hyp）含量评估抗纤维化作用。采用相对和绝对定量同位素标记（iTRAQ）方法和气相色谱 - 质谱联用（GC - MS）技术检测大鼠肝脏组织的蛋白质谱和代谢产物谱。通过蛋白质组学和代谢组学数据的综合分析，寻找变化的通路以及关键蛋白质和代谢产物。采用蛋白质印迹法测定变化通路中一些关键蛋白质的水平。
绞股蓝总皂苷组的组织病理学变化和Hyp含量有显著改善（P<0.05）。与肝纤维化模型组相比，绞股蓝总皂苷组发现301个上调蛋白和296个下调蛋白，以及9个上调代谢产物和8个下调代谢产物。综合分析发现一些重要通路，包括糖酵解或糖异生、果糖和甘露糖代谢、甘氨酸、丝氨酸和苏氨酸代谢、赖氨酸降解、精氨酸和脯氨酸代谢、谷胱甘肽代谢以及硫代谢。此外，发现ALDH1B1、ALDH2和ALDH7A1水平升高，绞股蓝总皂苷处理后恢复至正常水平（P<0.05）。
绞股蓝总皂苷抑制CCl4诱导的肝纤维化，可能与糖酵解代谢改变以及通过上调ALDH对醛类和脂质过氧化损伤的保护作用有关。
