corylin and Inflammation

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 VB. Corylin administration ameliorated DSS-induced colitis and inhibited intestinal inflammation and neuroinflammation via regulating the inflammation interactions across gut-brain axis and increasing 5-HTP generation in the colon.

Topics: 5-Hydroxytryptophan; Animals; Brain-Gut Axis; Chromatography, Liquid; Colitis; Colitis, Ulcerative; Colon; Dextran Sulfate; Disease Models, Animal; Flavonoids; Inflammation; Mice; Mice, Inbred C57BL; Molecular Docking Simulation; RNA, Ribosomal, 16S; Serotonin; Tandem Mass Spectrometry

Inflammation has been found to be associated with many neurodegenerative diseases, including Parkinson's and dementia. Attenuation of microglia-induced inflammation is a strategy that impedes the progression of neurodegenerative diseases.. We used lipopolysaccharide (LPS) to simulate murine microglia cells (BV2 cells) as an experimental model to mimic the inflammatory environment in the brain. In addition, we examined the anti-inflammatory ability of corylin, a main compound isolated from Psoralea corylifolia L. that is commonly used in Chinese herbal medicine. The production of nitric oxide (NO) by LPS-activated BV2 cells was measured using Griess reaction. The secretion of proinflammatory cytokines including tumor necrosis factor (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) by LPS-activated BV2 cells was analyzed using enzyme-linked immunosorbent assay (ELISA). The expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase-activation and recruitment domain (ASC), caspase-1, IL-1β and mitogen-activated protein kinases (MAPKs) in LPS-activated BV2 cells was examined by Western blot.. Our experimental results demonstrated that corylin suppressed the production of NO and proinflammatory cytokines by LPS-activated BV2 cells. In addition, corylin inhibited the expression of iNOS and COX-2, attenuated the phosphorylation of ERK, JNK and p38, decreased the expression of NLRP3 and ASC, and repressed the activation of caspase-1 and IL-1β by LPS-activated BV2 cells.. Our results indicate the anti-inflammatory effects of corylin acted through attenuating LPS-induced inflammation and inhibiting the activation of NLRP3 inflammasome in LPS-activated BV2 cells. These results suggest that corylin might have potential in treating brain inflammation and attenuating the progression of neurodegeneration diseases.

Topics: Animals; Cell Survival; Flavonoids; Inflammasomes; Inflammation; Lipopolysaccharides; Mice; Microglia; Mitogen-Activated Protein Kinases; NLR Family, Pyrin Domain-Containing 3 Protein; Phosphorylation; Signal Transduction