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.
Highlights
Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), are a group of chronically recurring inflammatory disorders characterised by the presence of intestinal inflammation and epithelial injury and associated with an increased risk of colorectal cancer[1,2]
Our results strongly suggest the importance of HQT in the maintenance of intestinal epithelial homeostasis and in the modulation of the inflammatory and immune response in dextran sodium sulphate (DSS)-induced colitis in mice
These results indicate a protective role of HQT during the progression of acute colitis
Summary
Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), are a group of chronically recurring inflammatory disorders characterised by the presence of intestinal inflammation and epithelial injury and associated with an increased risk of colorectal cancer[1,2]. Current therapeutic options for IBD include administration of mesalazine, immunosuppressive drugs, corticosteroids and monoclonal antibodies to tumour necrosis factor-α(TNF-α)[6] These agents are effective to various extents, they are associated with serious side effects, such as increased risk of infection, malignancy, and autoimmunity[7]. Huangqin-Tang (HQT) decoction is a traditional herbal formula described in the Chinese medicine book “Discussion of Cold Damage” (“Shang-Han-Lun” in Chinese) that has been used for nearly 1,800 years. It consists of 4 components: the roots of Scutellaria baicalensis Georgi. Our results strongly suggest the importance of HQT in the maintenance of intestinal epithelial homeostasis and in the modulation of the inflammatory and immune response in dextran sodium sulphate (DSS)-induced colitis in mice
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