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Abstract Background Huangkui Lianchang Decoction (HLD) is a traditional Chinese herbal formula for treating ulcerative colitis (UC). However, its mechanism of action remains poorly understood. The Study aims to validate the therapeutic effect of HLD on UC and its mechanism by integrating network pharmacology, bioinformatics, and experimental validation. Methods UC targets were collected by databases and GSE19101. The active ingredients in HLD were detected by ultra-performance liquid chromatography-tandem mass spectrometry. PubChem collected targets of active ingredients. Protein–protein interaction (PPI) networks were established with UC-related targets. Gene Ontology and Kyoto Encyclopedia (KEGG) of Genes and Genomes enrichment were analyzed for the mechanism of HLD treatment of UC and validated by the signaling pathways of HLD. Effects of HLD on UC were verified using dextran sulfate sodium (DDS)-induced UC mice experiments. Results A total of 1883 UC-related targets were obtained from the GSE10191 dataset, 1589 from the database, and 1313 matching HLD-related targets, for a total of 94 key targets. Combined with PPI, GO, and KEGG network analyses, the signaling pathways were enriched to obtain IL-17, Toll-like receptor, NF-κB, and tumor necrosis factor signaling pathways. In animal experiments, HLD improved the inflammatory response of UC and reduced UC-induced pro-inflammatory factors such as Tumor Necrosis Factor Alpha (TNF-α), interleukin 1β (IL-1β), and interleukin 6 (IL-6). HLD suppressed proteins TLR4, MyD88, and NF-κB expression. Conclusions This study systematically dissected the molecular mechanism of HLD for the treatment of UC using a network pharmacology approach. Further animal verification experiments revealed that HLD inhibited inflammatory responses and improved intestinal barrier function through the TLR4/MyD88/NF-κB pathway.

Abstract Background This study aimed to investigate a causal relationship between IBD and multiple kidney diseases using two-sample Mendelian randomization (MR) analyses. Methods We selected a group of single nucleotide polymorphisms (SNPs) specific to IBD as instrumental variables from a published genome-wide association study (GWAS) with 86,640 individuals of European ancestry. Summary statistics for multiple kidney diseases were obtained from the publicly available GWAS. Genetic data from one GWAS involving 210 extensive T-cell traits was used to estimate the mediating effect on specific kidney disease. Inverse-variance weighted method were used to evaluate the MR estimates for primary analysis. Results Genetic predisposition to IBD was associated with higher risk of IgA nephropathy (IgAN) (OR, 1.78; 95% CI, 1.45–2.19), but not membranous nephropathy, diabetic nephropathy, glomerulonephritis, nephrotic syndrome, chronic kidney disease, and urolithiasis. CD4 expression on CD4 + T cell had a significant genetic association with the risk of IgAN (OR, 2.72; 95% CI, 1.10–6.72). Additionally, consistent results were also observed when IBD was subclassified as ulcerative colitis (OR, 1.38; 95% CI, 1.10–1.71) and Crohn’s disease (OR, 1.37; 95% CI, 1.12–1.68). MR-PRESSO and the MR-Egger intercept did not identify pleiotropic SNPs. Conclusions This study provides genetic evidence supporting a positive casual association between IBD, including its subclassification as ulcerative colitis and Crohn’s disease, and the risk of IgAN. However, no casual association was found between IBD and other types of kidney diseases. Further exploration of IBD interventions as potential preventive measures for IgAN is warranted.