Mechanism Study of Foeniculi Fructus Volatile Oil Against Postoperative Ileus Based on Network Pharmacology and Molecular Docking

OBJECTIVE To investigate the molecular mechanism of the Foeniculi Fructus volatile oil in improving postoperative ileus(POI) based on network pharmacology, molecular docking and other data mining means. METHODS The volatile oil of Foeniculi Fructus was extracted and analyzed by GC-MS. Then the active compounds were screened. The potential effective targets of active compounds against POI were obtained by searching and analyzing the data from STITCH, Swiss, TCMSP and other databases. Protein-protein interaction network of potential effective targets was established and hub targets were acquired by topology analysis. GO and KEGG enrichment analyses were carried out through DAVID database. The expression of the hub targets in gastrointestinal tract were analyzed through HPA database. Molecular docking was used to analyze the binding between hub proteins and active compounds. RESULTS GC-MS results showed that 23 compounds were found in Foeniculi Fructus volatile oil. Among them, 5 compounds were first found in Foeniculi Fructus volatile oil. Then 10 hub targets(e.g., HMOX1, KDR, PTPRC, RELA) were obtained by screening. GO and KEGG analysis of the hub targets found that the active components in Foeniculi Fructus volatile oil mainly regulate PI3K-Akt, HIF-1 and NF-κB and other signaling pathways through hub targets (e.g., HMOX1, RELA, JAK2), then affecting biological processes(positive regulation of NO biosynthesis, negative regulation of exogenous apoptosis signal pathway mediated by death domain receptor, and so on). Most of the hub targets were abundantly distributed in gastrointestinal gland cells, and some of the hub targets were also distributed in gastrointestinal lymphocytes and peripheral nerves/ganglia. Molecular docking found that the active compounds could be embedded into the active pocket of the hub targets. CONCLUSION Foeniculi Fructus volatile oil is composed of several active components mainly anethole and terragon. They regulate multi-signaling pathways with PI3K/Akt signaling pathway as the core through HMOX1, RELA and other hub targets. Then the secretion of digestive tract glands and factors, intestinal nerve and inflammatory response are affected, which ultimately achieving improvement of POI. This study provides the basis for an in-depth study on the improvement of POI by Foeniculi Fructus volatile oil.