Bioactive ingredients obtained from Cortex Fraxini impair interactions between FAS and GPI

The high expression of fatty acid synthase (FAS) in tumor cells is consistent with their elevated requirement for fatty acids for cell membrane synthesis and energy supply to support their almost unlimited proliferation. The expression levels of FAS in tumor cells are related to their proliferation, invasion, and metastasis. This study investigated the possible bioactive ingredients (fraxin, esculetin, scopolin et al.) of Cortex Fraxini and their effects on the interaction between specific proteins. We used microscale thermophoresis (MST) to show that our target protein, FAS (screened by combining transcriptome and network pharmacology), bound to the active compounds in Cortex Fraxini. It was found that FAS bound strongly to Glucose-6-phosphate isomerase (GPI), and that scopolin could affect this interaction by proteomics and MST. The results of this study demonstrate that the active compounds in Cortex Fraxini could play an anti-tumor role by binding to FAS and inhibiting the interactions between FAS and GPI to affect glucose and lipid metabolism, and that the protein pathway is a potential novel target for tumor treatment. [Display omitted] •Binding components and proteins were screened out and their Kd were detected.•Isoscopoletin and scopolin competitively bind FAS with antibody.•We further inferred the binding region of isoscopoletin and scopolin.•Active compounds bind FAS and inhibit the interactions between FAS and GPI.•Active compounds may treat tumor by affecting glucose and lipid metabolism.