Abstract: Tea stem has a significant impact on the sensory quality for Fucha fermentation product. To explore the active ingredients and targets of tea stems in Fucha, Aspergillus cristatus LJSC.2006 (GenBank accession number: MZ147020) was used to ferment tea stem and obtain the end products. Non-targeted metabolomics (LC-MS/MS), network pharmacology, and molecular docking were used to verify the experimental results. Based on partial least squares discriminant analysis (OPLS-DA), 295 kinds of non-targeted metabolites with differential expression between the fermented tea stem and raw tea stem were identified, including 41 carbohydrates, 37 organic acids, 33 phenols and derivatives, 27 terpenoids, 26 amines, 24 nitrogen-containing heterocyclic compounds, 21 esters, 19 glyeosides, 15 flavonoids and derivatives, 14 amino acids and derivatives, 9 steroids and derivatives, 9 alkaloids, 6 phenolic acids, 6 coumarins and derivatives, 1 catechin and derivatives and 7 others. The network pharmacological analysis show that there were 16 potential active ingredients acting on 248 targets, and 13 potential central targets were obtained through Protein-Protein Interaction (PPI) screening. According to the results of molecular docking, coumestrol, galangin, luteolin and crocetin were the main central active ingredients. EGFR, ESR1, SRC and PTGS2 were the main targets of tea stem fermented by Aspergillus cristatus.

Key words: Aspergillus cristatus LJSC.2006, tea stem, non-targeted metabolomics, network pharmacology