Metabolic and microbial signatures in rat hepatocellular carcinoma treated with caffeic acid and chlorogenic acid.
Metabolic and microbial signatures in rat hepatocellular carcinoma treated with caffeic acid and chlorogenic acid.
复制标题
咖啡酸和绿原酸治疗大鼠肝细胞癌的代谢和微生物特征
DOI：
10.1038/s41598-017-04888-y
复制
发表时间：
2017-07-03
影响因子：
4.6
通讯作者：
Li L
中科院分区：
文献类型：
--
作者：
Zhang Z;Wang D;Qiao S;Wu X;Cao S;Wang L;Su X;Li L
肝细胞癌（HCC）的治疗仍缺乏有效的化学预防药物，因此，寻找新的抗HCC药物是非常有吸引力和迫切的。本研究观察了绿原酸（ChA）和咖啡酸（CaA）对二乙基亚硝胺（DEN）诱发肝癌的影响。ChA或CaA可降低肝组织病理学改变和肝损伤标志物丙氨酸转氨酶、天冬氨酸转氨酶、碱性磷酸酶、总胆汁酸、总胆固醇、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇。基于代谢组学数据和16 S rRNA基因测序数据的相关性分析，通过数据整合策略研究其潜在机制。ChA或CaA可抑制肝癌大鼠瘤球菌UCG-004的增加和不定毛螺菌、普雷沃菌9的减少。应用主成分分析和偏最小二乘判别分析揭示各组间的代谢差异。28种不同的代谢产物在CaA和ChA治疗中均显示恢复正常的趋势。其中胆红素、L-酪氨酸、L-蛋氨酸和乙醇胺与瘤胃球菌UCG-004的升高相关，与不确定毛螺菌和普雷沃菌9的降低相关。这些相关性可以被识别为HCC发病的代谢和微生物特征和潜在的治疗靶点。
Hepatocellular carcinoma (HCC) treatment remains lack of effective chemopreventive agents, therefore it is very attractive and urgent to discover novel anti-HCC drugs. In the present study, the effects of chlorogenic acid (ChA) and caffeic acid (CaA) on HCC induced by diethylnitrosamine (DEN) were evaluated. ChA or CaA could reduce the histopathological changes and liver injury markers, such as alanine transarninase, aspartate aminotransferase, alkaline phosphatase, total bile acid, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol. The underlying mechanisms were investigated by a data integration strategy based on correlation analyses of metabonomics data and 16 S rRNA gene sequencing data. ChA or CaA could inhibit the increase ofRumincoccaceae UCG-004and reduction ofLachnospiraceae incertae sedis, andPrevotella 9in HCC rats. The principal component analysis and partial least squares discriminant analysis were applied to reveal the metabolic differences among these groups. 28 different metabolites showed a trend to return to normal in both CaA and ChA treatment. Among them, Bilirubin, L-Tyrosine, L-Methionine and Ethanolamine were correlated increasedRumincoccaceae UCG-004and decreased ofLachnospiraceae incertae sedisandPrevotella 9. These correlations could be identified as metabolic and microbial signatures of HCC onset and potential therapeutic targets.