Material basis research for Echinacea purpurea (L.) Moench against hepatocellular carcinoma in a mouse model through integration of metabonomics and molecular docking

Echinacea purpurea (L.) Moench (EP), a well-known "immunostimulant" in the West, is one of the most popular botanicals for patients with cancer. It has been proved to be effective against hepatocellular carcinoma (HCC), while the active ingredients remains unclear.This study aimed to investigate the inhibitory effect and interpret the material basis of EP against HCC through metabolomics and molecular docking.Tumor growth, biochemical analysis and pathological changes were detected in HCC-induced mice to evaluate the efficacy of EP. An integrative method combining molecular docking and LC-MS-based metabolomics was performed to evaluate the inhibitory role and screen the material basis of EP against HCC.EP significantly suppressed tumor growth and decreased the levels of AFP. Histological analysis showed that wide areas of necrosis in the EP-treated tumors that were almost absent in those in model group. Serum metabolomics results revealed EP could significantly improve 12 serum different metabolites induced by HCC, which were involved into phenylalanine, tyrosine and tryptophan biosynthesis and phenylalanine metabolism. Then, 5 related genes were selected out to be the key targets of EP against HCC based on Metscape. 22 identified compounds were docked through Sybyl-X. The herb-compound-gene-metabolic pathways network (HCGMN) was constructed to reveal the associations between EP and HCC. Finally, 19 compounds were screened as promising active ingredients of EP against HCC.The results showed that the approach integrating of metabonomics and molecular docking is a powerful strategy to obtain the active ingredients from plants.