licochalcone-a and Colitis--Ulcerative

The gut epithelium is a mechanical barrier that protects the host from the luminal microenvironment and interacts with the gut microflora, which influences the development and progression of ulcerative colitis (UC). Licochalcone A (LA) exerts anti-inflammatory effects against UC; however, whether it also regulates both the gut barrier and microbiota during colitis is unknown. The current study was conducted to reveal the regulatory effects of LA on the intestinal epithelium and gut microflora in C57BL/6 mice subjected to dextran sodium sulfate (DSS). Sulfasalazine (SASP) was used as the positive control. Results of clinical symptoms evaluation, hematoxylin, and eosin (H&E) staining, and enzyme-linked immunosorbent (ELISA) assays showed that LA significantly inhibited DSS-induced weight loss, disease activity index (DAI) increase, histological damage, and gut inflammation. Additionally, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and immunohistochemical (IHC) analysis showed that LA maintained the integrity of the intestinal barrier by suppressing cell apoptosis and preserving the expression of tight junction (TJ) proteins. Notably, the optimal dose of LA for gut barrier preservation was low, while that for anti-inflammatory effects was high, indicating that LA might preserve gut barrier integrity via direct effects on the epithelial cells (ECs) and TJ proteins. Furthermore, 16S rRNA analysis suggested that the regulatory effect of LA on the gut microbiota differed distinctly according to dose. Correlation analysis indicated that a low dose of LA significantly modulated the intestinal barrier-associated bacteria as compared with a moderate or high dose of LA. Western blot (WB) analysis indicated that LA exhibited anti-UC activity partly by blocking the mitogen-activated protein kinase (MAPK) pathway. Our results further elucidate the pharmacological activity of LA against UC and will provide valuable information for future studies regarding on the regulatory effects of LA on enteric diseases.

Topics: Animals; Chalcones; Colitis; Colitis, Ulcerative; Colon; Dextran Sulfate; Disease Models, Animal; Gastrointestinal Microbiome; Intestinal Mucosa; Male; Mice; Mice, Inbred C57BL; Sulfasalazine; Tight Junction Proteins

Licochalcone A (Lico A) is a characteristic chalcone isolated from licorice root which is widely recognized in traditional Chinese medicine for the ability of anti-inflammatory, antioxidant, anti-parasitic and anti-cancer. The present study was aimed to investigate the effect of Lico A on dextran sulphate sodium (DSS)-induced ulcerative colitis (UC) in a mouse model which was induced by administration of 3% DSS in drinking water. Mice were then treated with Lico A (20, 40 and 80 mg/kg, p.o.) or 0.9% saline (20 ml/kg, p.o.) for 17 days. The results showed that treatment with Lico A significantly reduced the colon length, histological damage scores, and colonic myeloperoxidase (MPO) activity in a dose-dependent manner as compared to the UC control group. Besides, Lico A significantly decreased the oxidative stress and pro-inflammatory cytokines, downregulated nuclear transcription factor kappa B (NF-κB) pathway and upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Collectively, Lico A is effective in alleviating DSS-induced colitis in mice and the mechanism is associated with its inhibition of NF-κB-regulated pro-inflammatory signaling and activation of Nrf2-regulated cytoprotective protein expression.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Biomarkers; Body Weight; Chalcones; Colitis, Ulcerative; Colon; Cyclooxygenase 2; Cytokines; Dextran Sulfate; Male; Mice, Inbred C57BL; Models, Biological; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Peroxidase; Protective Agents; Signal Transduction