Huangqin-tang ameliorates dextran sodium sulphate-induced colitis by regulating intestinal epithelial cell homeostasis, inflammation and immune response

Abstract

Huangqin-tang (HQT) is a traditional Chinese medicine (TCM) formula widely used for the treatment of inflammatory bowel disease in China. However, the molecular mechanisms by which HQT protects the colon are unclear. We studied the protective effects of HQT and the underlying mechanisms in an experimental mouse model and in vitro. In vivo, dextran sodium sulphate (DSS)-induced acute and chronic colitis were significantly ameliorated by HQT as gauged by phenotypic, histopathologic and inflammatory manifestations of the disease. Mechanistically, DSS-induced nuclear factor-κB (NF-κB) signalling was inhibited by HQT. Moreover, HQT-treated mice demonstrated significant changes in cell apoptosis, expression of apoptosis-associated genes such as caspase-3, bax, bcl-2, and intestinal permeability. HQT also increased occluding and zonula occludens-1 (ZO-1), inhibited cell proliferation (Ki67), and increased regulatory T cells numbers, protein expression of Foxp3 and IL-10 in the colonic tissue. In vitro, HQT down-regulated production of pro-inflammatory cytokines and supressed the NF-κB signalling pathway in lipopolysaccharides-induced RAW 264.7 macrophages. Our study suggests that HQT plays a critical role in regulating intestinal epithelial cell homeostasis, inflammation and immune response in colitis and offers novel therapeutic options in the management of inflammatory bowel disease.

Fasting-Mimicking Diet Modulates Microbiota and Promotes Intestinal Regeneration to Reduce Inflammatory Bowel Disease Pathology

“…The acute DSS model is implemented over 1–2 weeks and is used to achieve short-term alterations in the intestinal barrier, whereas the chronic DSS mouse model is implemented over a period of 2–4 months to cause long-term effects on intestinal immunity and damage, serving as an effective model for chronic colitis (Wirtz et al, 2017). Because genetic factors for IBD are currently not well-established and only account for a portion of IBD, with one study finding that only 12% of UC patients have a familial history of IBD (Zhang and Li, 2014; Childers et al, 2014), the chronic DSS mouse model is particularly appropriate to model IBDs triggered by environmental factors (Schippers et al, 2016; Hoffmann et al, 2017; Zou et al, 2016). …”

Periostin attenuates tumor growth by inducing apoptosis in colitis-related colorectal cancer

“…Histologic scoring was performed by an investigator blinded to the project based on previously described criteria [ 15 ]. 0 = normal; 1 = moderate mucosal inflammation without erosion and ulcer; 2 = severe mucosal inflammation with erosion; 3 = severe mucosal inflammation with ulcer (< 1 mm); 4 = severe mucosal inflammation with ulcer (1–3 mm); 5 = severe mucosal inflammation with ulcer (> 3 mm).…”

Anti-Inflammatory Effects of Huangqin Decoction on Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice Through Regulation of the Gut Microbiota and Suppression of the Ras-PI3K-Akt-HIF-1α and NF-κB Pathways

“…(jujube, 49 g). Recent studies showed that HQD alleviated inflammation through suppression of the nuclear factor-kappa B (NF-kB) pathway and regulation of the gut microbiota to improve the intestinal microenvironment in mouse models of dextran sulfate sodium (DSS)-induced UC (Chen et al, 2016;Zou et al, 2016;Yang et al, 2017). However, these studies did not clarify how the gut microbiota exerted effects on inflammatory pathways.…”