Metabolomic study of the intervention effects of Shuihonghuazi Formula, a Traditional Chinese Medicinal formulae, on hepatocellular carcinoma (HCC) rats using performance HPLC/ESI-TOF-MS

Ethnopharmacological relevance Metabolomics is the comprehensive assessment of endogenous metabolites of a biological system in a holistic context, and its property consists with the global view of Traditional Chinese Medicine (TCM). Shuihonghuazi Formula (SHHZF) has been used for liver cancer early treatment in clinical for more than thirty years, but its mechanism remains unclear completely. This paper was designed to explore the therapeutic effects of SHHZF on liver cancer and its metabolomic characters. Materials and methods All the rats were given diethylnitrosamine (DEN) at the dosage of 70 mg/kg for 14 weeks. From the 7th weeks, SHHZF was given to the rats which lasted for 10 weeks. Therapeutic effects of SHHZF was compared with that of cyclophosphamide (CTX). High performance liquid-chromatography/electrospray-ionization time of flight mass spectrometer (HPLC/ESI-TOF-MS) combined with pattern recognition approaches including principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), was integrated to approximate the comprehensive metabolic signature and discover differentiating metabolites by Agilent MPP 12.1. The changes in metabolic profiling in plasma were restored to their baseline values after SHHZF treatment according to the PLS-DA score plots. Results The results indicated that 23 ions as “differentiating metabolites”. The alterations in those metabolites were associated with perturbations in fatty acid and bile acid metabolism, in response to liver cancer through immune and nervous system. And SHHZF could increase the uptake and utilization of linoleic acid and oleic acid, increase arachidonic acid-like substance content and enhance organism immunity of liver cancer rats. And it also could increase the translation from phosphatidylethanolamine (PE) to phosphatidylcholine (PC), linoleic acid metabolism and inhibits abnormal metabolism of bile acid. Conclusions The mechanism of therapeutic effects of SHHZF on liver cancer by adjusting the activities of PE N-methyl transferase (PEMT), Lysophospholipase D, methylenetetrahydrofolate reductase (MTHFR) and lysophospholipase was elucidated by the method of metabonomics for the first time.