Corylin ameliorates chronic ulcerative colitis via regulating the gut–brain axis and promoting 5-hydroxytryptophan production in the colon

• Published in: Phytomedicine (Stuttgart) 2023-02, Vol.110, p.154651-154651, Article 154651
• Main Authors: Wang, Zhao-Jing, Chen, Li-Hua, Xu, Jing, Xu, Qing-Xia, Xu, Wei, Yang, Xiu-Wei
• Format: Article
• Language: English
• Subjects: 5-hydroxytryptophan; 5-Hydroxytryptophan - pharmacology; Animals; Brain-Gut Axis; Chromatography, Liquid; Chronic ulcerative colitis; Colitis - chemically induced; Colitis - drug therapy; Colitis, Ulcerative - chemically induced; Colitis, Ulcerative - drug therapy; Colon; Corylin; Dextran Sulfate; Disease Models, Animal; Flavonoids; Gut–brain axis; Inflammation; Mice; Mice, Inbred C57BL; Molecular Docking Simulation; RNA, Ribosomal, 16S; Serotonin; Tandem Mass Spectrometry
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2023.154651

•Corylin alleviates colonic inflammation and neuroinflammation in chronic UC mice.•Corylin improves intestinal mucosal barrier and blood–brain barrier damage.•Corylin reverses level changes of neurotransmitters in the colon, serum, and brain of chronic UC mice.•Binding of corylin to 5-HTPDC induced enzyme degradation resulting in the 5-HTP accumulation.•Corylin modulates the diversity and composition of the intestinal microbiota. Chronic ulcerative colitis (UC) is a lifelong disease, patients with chronic UC have a high prevalence of common mental disorders. The increasing interest in the role of gut-brain axis is seen in inflammatory bowel diseases. Corylin is a representative flavonoid compound isolated from the Psoraleae Fructus. This study aimed to identify the effects and mechanism of corylin on the inflammation interactions and 5-HT synthesis between the gut and brain in chronic UC. Dextran sulfate sodium (DSS) induced chronic UC mouse model was established to assess the therapeutic effect of corylin on chronic UC symptoms. The expression of inflammatory cytokines was detected in the colon and brain. The expression of tight junction (TJ) proteins of intestinal mucosal barrier and blood–brain barrier (BBB) and the ionized calcium-binding adaptor molecule 1 (Iba1) in the hippocampus were determined by western blotting and immunofluorescence staining. In addition, several tryptophan (Trp) metabolites and related neurotransmitters in faeces, colon, serum, and brain were detected by UPLC-MS/MS. The interaction between corylin and 5-hydroxytryptophan decarboxylase (5-HTPDC) was performed by molecular docking and surface plasmon resonance (SPR). Finally, the changes of gut microbiota composition were analyzed by 16S rRNA sequencing. Corylin significantly alleviated colitis symptoms and inhibited inflammatory response in the colon and brain of DSS-induced chronic UC mice. The TJ proteins of intestinal mucosal barrier and BBB were improved and the expression of Iba1 in the hippocampus was normalized after corylin treatment. In addition, corylin treatment increased the expression of neurotransmitters in the brain, especially 5-hydroxytryptamine (5-HT) and 5-hydroxytryptophan (5-HTP), but the expression of 5-HT in the colon was inhibited. Further study firstly proved that corylin could bind to the 5-HTDPC, and then inhibit the expression of 5-HTDPC and VB6, resulting in the 5-HT reduction and 5-HTP accumulation in the colon. Moreover, the intake of corylin tran