Abstract
ObjectiveHuangqin decoction (HQD), a classical traditional Chinese medicinal formula, has been commonly used to treat gastrointestinal diseases for thousands of years. We investigated the anti-inflammatory effects and underlying mechanisms of HQD on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC).MethodsExperimental mice were given 3% DSS, and HQD (2.275, 4.55, and 9.1 g/kg), or mesalazine (ME, 200 mg/kg) orally for 7 days. Body weight loss, disease activity index (DAI), colon length, histology, and levels of inflammatory cytokines were measured to evaluate the effects of HQD on colitis. The effects of HQD on the Ras-phosphoinositide-3-kinase (PI3K)-Akt-hypoxia inducible factor 1 alpha (HIF-1α) and nuclear factor-kappa B (NF-κB) pathways were evaluated by Western blot analysis. In addition, the gut microbiota was characterized using high-throughput Illumina MiSeq sequencing.ResultsThe results showed that HQD significantly reduced the body weight loss, ameliorated DAI, restored colon length, and improved the intestinal epithelial cell barrier in mice with DSS-induced colitis. The messenger RNA (mRNA) expression levels of inflammatory mediators were decreased following HQD treatment. Furthermore, the Ras-PI3K-Akt-HIF-1α and NF-κB pathways were significantly inhibited by HQD. Finally, treatment with HQD resulted in recovery of gut microbiota diversity.ConclusionsHQD ameliorates DSS-induced colitis through regulation of the gut microbiota, and suppression of Ras-PI3K-Akt-HIF-1α and NF-κB pathways. Our results suggested that HQD may be a potential candidate for treatment of UC.
Highlights
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon and rectum with unclear etiology
We investigated the molecular mechanisms of Huangqin decoction (HQD) in a murine model of dextran sulfate sodium (DSS)-induced colitis by measuring the expression levels of inflammatory cytokines, receptors, and proteins in the Ras-PI3K-Akt-hypoxia inducible factor 1 alpha (HIF-1a) and nuclear factor-kappa B (NF-kB) pathways
Primers for G protein-coupled receptors (GPCR), toll-like receptor 4 (TLR4), mannose receptor (MR), triggering receptor expressed on myeloid cells 2 (Trem2), inducible nitric oxide synthase, CXC chemokine ligand 10 (CXCL10), interleukin-1b (IL-1b), interleukin-6 (IL-6), interleukin-4 (IL-4), interleukin-10 (IL10), and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) were synthesized by Shanghai Sangon Biotech Co., Ltd. (Shanghai, China)
Summary
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon and rectum with unclear etiology. Recent studies showed that UC is a chronically recurring inflammatory disorder, characterized by intestinal inflammation and dysregulation of the mucosal epithelial barrier, which is one of the three greatest risk factors for development of colorectal cancer (CRC). Current treatments for UC include mesalazine (ME), sulfasalazine, immunosuppressive drugs, corticosteroids, and interferons. These drugs are associated with side effects such as nausea, headache, and dizziness (Ross and Cohen, 2004). Many complementary and alternative medicinal (CAM) approaches have been shown to be effective for treatment of IBD (Maciej et al, 2014). Development of novel efficient and safe therapeutic strategies for treatment of IBD is needed
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