Fuzheng Xiaozheng prescription relieves rat hepatocellular carcinoma through improving anti-inflammation capacity and regulating lipid related metabolisms

J Ethnopharmacol. 2022 Feb 10:284:114801. doi: 10.1016/j.jep.2021.114801. Epub 2021 Nov 5.

Abstract

Ethnopharmacological relevance: Fuzheng Xiaozheng prescription (FZXZP) is a traditional Chinese medicine (TCM) that was derived from Sanjiasan, a famous decoction documented in the book of Wenyilun in Ming dynasty. Based on our years' clinic application, FZXZP demonstrated satisfactory therapeutic effects in cirrhosis and hepatocellular carcinoma (HCC) treatments. However, the underlying mechanisms are still largely unknown.

Aim of study: In this study, we aim to systematically evaluate the intervention effects of FZXZP on rat HCC and deeply elucidate the underlying regulative mechanisms on rat HCC.

Materials and methods: The HCC rats were induced by using diethylnitrosamine (DEN) and two doses of FZXZP were adopted to treat the HCC rats. Liver phenotype, blood chemistry and liver histopathology were used to evaluate the intervention effects. High performance liquid chromatography (HPLC) was conducted to analyze the components of FZXZP. Finally, miRNA-Seq and mRNA-Seq were performed to investigate the regulative mechanisms of FZXZP on rat HCC and qRT-PCR was carried out to verify the accuracies of the two RNA-Seqs.

Results: Results of liver phenotypes, blood chemistry and liver histopathology demonstrated that FZXZP significantly alleviated the liver damage, inhibited the progresses of HCC. Nine potential components were identified from FZXZP, and anti-cancer prediction suggested that almost all of them were reported to show an anti-cancer effect. Mechanistically, FZXZP was found to promote the lipid related metabolisms, improve the anti-inflammation ability by activating PPAR signaling pathway, arachidonic acid metabolism, bile secretion, etc. CONCLUSION: our results suggested that FZXZP significantly alleviated the rat HCC, mechanistically by improving the anti-inflammation ability and promoting the lipid related metabolisms.

Keywords: Anti-inflammation; Fuzheng Xiaozheng prescription; HCC; Lipid related metabolism; mRNA; miRNA.

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Hepatocellular* / chemically induced
  • Carcinoma, Hepatocellular* / drug therapy
  • Diethylnitrosamine / toxicity
  • Drugs, Chinese Herbal* / therapeutic use
  • Gene Expression Regulation, Neoplastic / drug effects
  • Liver / drug effects
  • Liver / pathology
  • Liver Neoplasms* / chemically induced
  • Liver Neoplasms* / drug therapy
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Neoplasms, Experimental / drug therapy
  • Phytotherapy*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Transcriptome

Substances

  • Antineoplastic Agents
  • Diethylnitrosamine
  • Drugs, Chinese Herbal
  • MicroRNAs
  • RNA, Messenger
  • Fuzheng Xiaozheng