关键词: 刺梨黄酮；溃疡性结肠炎；网络药理学；分子对接；花生四烯酸代谢

Abstract: The aim of this study was to investigate the core components and mechanism of action of Rosa roxburghii fruit flavonoids in the intervention of ulcerative colitis (UC) using network pharmacology and molecular docking. We extracted flavonoids from R. roxburghii fruit by an ethanol-cellulase method and used liquid chromatography-mass spectrometry (LC-MS) to identify the major chemical components of the flavonoid extract, and then we selected 34 active flavonoid components and 146 targets in the intervention of UC on an analytical platform and constructed a “R. roxburghii flavonoids-active components-intersecting targets-UC” network. The results of gene ontology pathway analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the intervention of R. roxburghii flavonoids in UC mainly involved the arachidonic acid signaling pathway, the nuclear factor-kappa B signaling pathway, and cancer pathways. Molecular docking was performed on the major active ingredients and the key targets selected from the network, with docking energies all less than −6.0 kcal/mol, indicating a strong binding affinity between the core active ingredients and the key targets for UC treatment. So, the network analysis results are reliable. The results of animal experiments showed that intervention with R. roxburghii flavonoids could effectively alleviate the body mass loss and colon pathological changes of UC mice, and significantly inhibit the expression of inflammatory cytokines such as tumour necrosis factor-α, interleukin (IL)-1β and IL-6 in the UC model group (P < 0.05). The results of Western blot showed that R. roxburghii flavonoids could effectively inhibit the expression of the key target proteins associated with the metabolic pathway of arachidonic acid, such as cyclooxygenase-2 and 5-lipoxygenase. In conclusion, R. roxburghii flavonoids can intervene in UC through a multi-component, multi-target and multi-pathway mechanism. The results of this research can provide a theoretical basis for the development and utilization of functional foods from R. roxburghii.

Key words: Rosa roxburghii flavonoids; ulcerative colitis; network pharmacology; molecular docking; arachidonic acid metabolism