Kui Jie Tong Ameliorates Ulcerative Colitis by Regulating Gut Microbiota and NLRP3/Caspase-1 Classical Pyroptosis Signaling Pathway

Abstract

Ulcerative colitis (UC) is one of the most refractory digestive diseases in the world. Kui jie tong (KJT) is an effective traditional Chinese medicine used clinically to treat UC. This study observed the regulatory effects of KJT on NIMA-related kinase 7- (NEK7-) activated nod-like receptor protein-3 (NLRP3)/caspase-1 classical pyroptosis pathway and intestinal flora in UC model rats. KJT components were analyzed using an ultraperformance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS). A UC Sprague Dawley (SD) rat model was established using sodium dextran sulfate (DSS). Rats were randomly divided into four groups: control group (CG), UC model group (UG), KJT group (KG), and sulfasalazine (SASP) group (SG). After seven days of intervention, each group’s body weight, disease activity index (DAI) scores, and colon length were recorded. Intestinal mucosal injury to each group was observed using hematoxylin-eosin staining. Additionally, we investigated the expression levels of NEK7, NLRP3, ASC, caspase-1, and GSDMD in intestinal mucosa, as well as serum interleukin- (IL-) 1β, IL-18, and IL-33 proinflammatory factors. Intestinal microflora was analyzed using 16s rRNA sequencing. KJT controlled weight loss; decreased DAI scores; restored colon length; improved pathological injury in the colon; inhibited NEK7, NLRP3, ASC, caspase-1, cleaved-caspase-1, GSDMD, and GSDMD-N expression; and decreased IL-1β, IL-18, and IL-33 contents in UG rats’ serum and colon tissue (P <0.001 or P <0.05). KJT also increased Ruminococcaceae, unclassified_f_Ruminococcaceae, and unclassified_g_Ruminococcus_1 levels and decreased Erysipelotrichia, Erysipelotrichales, Erysipelotrichaceae, Turicibacter, and uncultured_bacterium_g_Turicibacter levels. KJT alleviated UC immune-inflammatory responses to NLRP3/caspase-1 by inhibiting the NEK-7-activated classic pyroptosis pathway and improving intestinal microflora.

Pharmacology Mechanism of Polygonum Bistorta in Treating Ulcerative Colitis Based on Network Pharmacology

“…As shown in Figures11 and 12, IL-17A, B, C, E, and F can bind to Act1/TRAF3IP2 and TRAF6 through diferent IL-17 receptors (IL-17RA, B, C, and E) and further regulate AP-1(Fos/Jun) to promote the release of proinfammatory cytokines and chemokines. DSS can induce colitis in mice[51][52][53] and rats[54][55][56]. Te expressions of Act1/TRAF6/FOS/JUN of the IL-17 signaling pathway in Caco-2 cells were increased after being stimulated with DSS in our experiment.…”

Atractylodes macrocephala Koidz. volatile oil relieves acute ulcerative colitis via regulating gut microbiota and gut microbiota metabolism

“…We also dug deeper into the changes of GM at the genus level and expect to screen out specific microorganisms potentially responsible for the efficacy of AVO. The increased Turicibacter had been observed in many UC individuals, and Turicibacter was positively associated with inflammation ( 24 , 25 ). In our study, Turicibacter was conspicuously increased after the DSS challenge, and oral AVO decreased Turicibacter which has been increased by DSS.…”

The potential mechanism of huazhuojiedu decoction in the treatment of ulcerative colitis based on network pharmacology and experimental validation

“…The NLRP3/ caspase-1 signaling pathway is a classical signaling pathway for pyroptosis (Burdette et al, 2021). Shigui Xue et al found that inhibition of the NLRP3/caspase-1 pathway was an effective way to improve DSS rats (Xue et al, 2022), which was supported by data from Hu et al (2021). The NLRP3/caspase-1 pathway exerts a vital role in UC by regulating pyroptosis.…”