Abstract
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 of Rumincoccaceae UCG-004 and reduction of Lachnospiraceae incertae sedis, and Prevotella 9 in 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 increased Rumincoccaceae UCG-004 and decreased of Lachnospiraceae incertae sedis and Prevotella 9. These correlations could be identified as metabolic and microbial signatures of HCC onset and potential therapeutic targets.
Highlights
Hepatocellular carcinoma (HCC) is a global problem and the second most common cause of cancer related deaths in the world[1, 2]
The effects of caffeic acid (CaA) or chlorogenic acid (ChA) on composition of gut microbiota associated with HCC remain unclear
The effects of CaA and ChA on HCC induced by diethylnitrosamine (DEN) were evaluated
Summary
Hepatocellular carcinoma (HCC) is a global problem and the second most common cause of cancer related deaths in the world[1, 2]. Primary prevention of HCC can be achieved with universal vaccination against Hepatitis B virus (HBV) infection[3] Owing to their characteristics of high chemical diversity and biochemical specificity, a broad spectrum of phytochemicals including flavonoids, alkaloids and polyphenols, has been isolated and investigated for anti-HBV activities[4]. The effects of CaA or ChA on composition of gut microbiota associated with HCC remain unclear. Metabolomics is a rapidly evolving technology for identifying novel biomarkers by assessing large numbers of metabolites that are substrates and products in metabolic pathways. It is a new avenue for understanding of cellular and organism specific responses to environment, chemicals and drugs perturbations[16]. The functional relationships between metabolites and gut microbial composition was investigated by a data integration strategy based on correlation analyses of serum metabonomics data and 16 S rRNA gene sequencing data
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