Metabolic and microbial signatures in rat hepatocellular carcinoma treated with caffeic acid and chlorogenic acid

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.

Phenolic Acids of Plant Origin—A Review on Their Antioxidant Activity In Vitro (O/W Emulsion Systems) Along with Their in Vivo Health Biochemical Properties

“…CA and its derivatives, such as CAPE, have been reported to act against colon cancer through their cytotoxic to tumors but not to normal cells [95]. In addition, Zhang et al 2017 [96] examined the action of CA (100 mg/kg) on structural changes caused by HCC in the rat microbiota. The authors concluded that this phenolic compound reduces certain biomarkers that indicate liver injury (among other alanine, transaminase, aspartate aminotransferase, alkaline phosphatase, total bile acid and total cholesterol).…”

“…CA chemoprotective effect on cell proliferation, p56 activation of hepatic tumors (HCC). [92] CA (100 mg/kg) in the rat microbiota CA reduce certain biomarkers that indicate liver injury [96] Carnosic acid (CarA)…”

Integrated analysis of microbiome and host transcriptome reveals correlations between gut microbiota and clinical outcomes in HBV-related hepatocellular carcinoma

“…The gut microbiota is known as the most important microecological system in symbiosis with the human body; moreover, several clinical characteristics (age, body mass index, dietary habits, and physical exercise) were found to differentially affect the gut microbiome of healthy Chinese people [ 3 ]. Liver diseases, such as nonalcoholic fatty liver disease (NAFLD) and liver cirrhosis, are often associated with altered gut microbiota, and it has been suggested that gut bacterial products contribute to liver carcinogenesis [ 4 – 7 ]. Recent studies in animal models or in patients with a background of NAFLD have indicated that some specific gut microbes promote HCC tumorigenesis through the gut-liver axis [ 8 – 10 ].…”

Maternal Consumption of a Low-Isoflavone Soy Protein Isolate Diet Accelerates Chemically Induced Hepatic Carcinogenesis in Male Rat Offspring

“…Since the liver is the major organ of lipoprotein synthesis and catabolism, serum lipid levels, particularly HDL-cholesterol, may be useful indicators in explaining the liver disease development, including HCC [35]. Accordingly, serum HDL-cholesterol levels were significantly decreased in HCC patients [36] and in DEN-injected rats [37] compared with the controls.…”