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Anorexia nervosa (AN) is a severe and complex psychiatric disorder with the highest mortality rate of all psychiatric disorders. Previous observational studies indicated inconclusive association between inflammatory bowel disease (IBD) and AN, and the causal effect remains unclear. We aimed to test the hypothesis that a causal relationship exists between IBD and the risk of AN using the bi-directional two-sample Mendelian randomization (MR) analysis. The inverse-variance weighted (IVW) method was employed as the primary analysis. Furthermore, various sensitivity analyses were conducted to assess the robustness of our results. Notably, IVW analysis of univariable MR revealed that genetically predicted IBD were significantly casually associated with AN risk. In subgroups, consistent positive causal associations with AN might show in ulcerative colitis (UC) and Crohn's disease (CD). Besides, there was no heterogeneity and horizontal pleiotropy observed in the sensitivity analysis. Our study identifies that genetic susceptibility to IBD (NSNP = 12, odds ratio [OR]: 1.143, 95% CI: 1.032–1.266, P = 0.01), including UC (NSNP = 6, OR: 1.153, 95% CI: 1.022–1.301, P = 0.021) and CD (NSNP = 4, OR: 1.153, 95% CI: 1.008–1.319, P = 0.037), could be causally associated with an increased risk of AN. No evidence was observed on the causal effect of AN on IBD, including UC and CD. Our findings may have clinical benefits for early detection of AN and clinical decisions on management of IBD patients. [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders affecting the digestive tract, including ulcerative colitis and Crohn's disease. Ruscogenin, a prominent steroidal sapogenin present in radix ophiopogon japonicus, has shown a protective effect on attenuating the inflammatory response associated with inflammatory diseases, but the efficacy of ruscogenin in IBD remains unclear. The aim of this study is to explore the effect of ruscogenin on intestinal barrier dysfunction and inflammatory responses as well as the underlying mechanism in ulcerative colitis. A dextran sulfate sodium salt (DSS)-induced C57BL/6 mouse colitis model was employed for the in vivo studies, while in vitro experiments were performed in THP-1 cells and human intestinal epithelial cells involved in inducing inflammatory responses and pyroptosis using LPS/nigericin. The results indicated that ruscogenin treatment attenuated the symptoms of ulcerative colitis, reduced the release of inflammatory cytokines and the expression of pyroptosis-associated proteins, and restored the integrity of the intestinal epithelial barrier in colon tissue in mice. Moreover, ruscogenin inhibited LPS/nigericin-induced pyroptosis in THP-1 cells. Mechanically, ruscogenin inhibited NLRP3 inflammasome activation and canonical pyroptosis, at least in part, through the suppression of the TLR4/NF-κB signaling pathway. These findings might provide new insights and a solid foundation for further exploration into the therapeutic potential of ruscogenin in the treatment of IBD. [ABSTRACT FROM AUTHOR]

Ulcerative colitis is a chronic inflammatory bowel disorder that is hard to cure once diagnosed. Bisdemethoxycurcumin has shown positive effects on inflammatory diseases. However, the underlying bioactive interaction between bisdemethoxycurcumin and ulcerative colitis is unclear. The objective of this study was to determine the core target and potential mechanism of action of bisdemethoxycurcumin as a therapy for ulcerative colitis. The public databases were used to identify potential targets for bisdemethoxycurcumin and ulcerative colitis. To investigate the potential mechanisms, the protein-protein interaction network, gene ontology analysis, and Kyoto encyclopedia of genes and genomes analysis have been carried out. Subsequently, experimental verification was conducted to confirm the findings. A total of 132 intersecting genes of bisdemethoxycurcumin, as well as ulcerative coli-tis-related targets, were obtained. SRC, EGFR, AKT1, and PIK3R1 were the targets of highest potential, and the PI3K/Akt and MAPK pathways may be essential for the treatment of ulcerative colitis by bisdemethoxycurcumin. Molecular docking demonstrated that bisdemethoxycurcumin combined well with SRC, EGFR, PIK3R1, and AKT1. Moreover, the in vitro experiments suggested that bisdemethoxycurcumin might reduce LPS-induced pro-inflammatory cytokines levels in RAW264.7 cells by suppressing PI3K/Akt and MAPK pathways. Our study provided a comprehensive overview of the potential targets and molecular mechanism of bisdemethoxycurcumin against ulcerative colitis. Furthermore, it also provided a theoretical basis for the clinical treatment of ulcerative colitis, as well as compelling evidence for further study on the mechanism of bisdemethoxycurcumin in the treatment of ulcerative colitis. [ABSTRACT FROM AUTHOR]